The Bug Parade Clinical Microbiology

Clinical Microbiology
The Bug Parade
www.theopenhydrant.com
©2011
The Bug Parade- 2011
Carboxy Penicillins .................................. 17

Penicillinase resistant Penicillins ............. 17
Table of Contents
*B-lactamase inhibitors .......................... 17
Bacteria Overview: 10
Cephalosporins ........................................... 17
General Terminology/Basics: ...................... 10
First generation ....................................... 18
Important Enzymes/Metabolic Pathways: .. 10
Second Generation ................................. 18
Exotoxins:.................................................... 12
Third Generation ..................................... 18
Alteration of cellular components .......... 12
Fourth Generation .................................. 18
Superantigens ......................................... 12
Aztreonam (a monobactam) ....................... 18
Inhibition of protein synthesis ................ 12
Carbapenems .............................................. 18
Increased synthesis of cAMP................... 12
Vancomycin ................................................ 18
Altered Nerve Impulse Transmission ...... 12
Aminoglycosides ......................................... 19
Taxonomy: .................................................. 13
Quinupristin/Dalfopristin ............................ 19
Gram Stain: ............................................. 13
Linezolid ...................................................... 19
Acid-Fast Staining:................................... 13
Mupirocin (Bactroban) ................................ 19
Selective Growth Media/Cultures ........... 13
Tetracyclines: .............................................. 20
Antimicrobials: 14
Macrolides .................................................. 20
General Principles: ...................................... 14
Clindamycin ................................................ 20
Bug Hints ..................................................... 14
Chloramphenicol ......................................... 21
SPACE Bug treatment: ............................. 14
Sulfonamides .............................................. 21
Anaerobe Coverage ................................ 14
Trimethoprim .............................................. 21
Atypical Coverage ................................... 14
TMP-SMX .................................................... 22
Enterococcus Coverage: .......................... 15
Nitrofurantoin ............................................. 22
Overview of antimicrobial MoA's: ............... 16
Methenamine ............................................. 22
Bacteriostatics: ....................................... 16
Quinolones.................................................. 23
Bacteriocidals: ......................................... 16
Rifampin...................................................... 24
Mechanisms of Resistance .......................... 16
Isoniazid (INH) ............................................. 24
Bug-Drugs: 17
Pyrazinamide (PZA) ..................................... 24
Penicillins .................................................... 17
Ethambutol ................................................. 24
Penicillin G .............................................. 17
Rifabutin ..................................................... 25
Aminopenicillins ...................................... 17
Rifapentine ................................................. 25
Uriedopenicillins ..................................... 17
www.theopenhydrant.com Page 2
Clofazamine ................................................ 25 Bacilli........................................................... 34

Dapsone ...................................................... 25 Bacillus Cereus ........................................ 34
Contrindicated in Pregnancy: ...................... 25 Bacillus Anthracis .................................... 34
Hints- From myself and First Aid ............ Error! Clostridium Tetani ................................... 35
Bookmark not defined. Clostridium Botulinum ............................ 35
Classification Overview: 27 Clostridium Difficilie ................................ 35
Gram Positive Bugs: .................................... 27 Clostridium Perfringens .......................... 36
Cocci........................................................ 27 Listeria Monocytogenes .......................... 36
Bacilli ....................................................... 27 Corynebacterium Diphtheria .................. 36
Beaded Filaments.................................... 27 Beaded Filaments ....................................... 37
Gram Negative Bugs: .................................. 28 Actinomyces Israelii ................................ 37
Diplococci ................................................ 28 Nocardia Asteroides ................................ 37
Bacilli ....................................................... 28 Nocardia Brasiliensis ............................... 37
Coccobacilli (pleomorphic) ...................... 28 Gram Negative Bacteria: 38
The "Other" Bugs: ....................................... 29 Diplococci.................................................... 38
Acid-Fast ................................................. 29 Neisseria Meningitidis ............................. 38
Spirochetes ............................................. 29 Neisseria Gonorrhoeae ........................... 38
Non-Gram Staining.................................. 29 Bacilli........................................................... 40
Gram Positive Bacteria 30 Escherischia Coli ...................................... 40
Cocci............................................................ 30 Klebsiella Pneuomoniae .......................... 41
Staphylococcus Aureus ........................... 30 Klebsiella Granulomatis .......................... 41
Staphylococcus Epidermidis .................... 30 Pseudomonas Aeruginosa ....................... 41
Staphylococcus Saprophyticus ................ 31 Eikenella Corrodens ................................ 41
Group A Streptococcus Pyogenes- .......... 31 Vibrio Cholera ......................................... 42
Streptococcus Agalactiae (Group B Step) 31 Vibrio Vulnificus ...................................... 42
Streptococcus Bovis (Group D) ............... 32 Vibrio Parahaemolyticus ......................... 42
Enterococcus Faecalis (Group D)............. 32 Proteus Mirabilis ..................................... 42
Streptococcus Pneumoniae .................... 32 Salmonella Typhi ..................................... 42
Streptococcus Mutans ............................ 33 Salmonella Enteriditis ............................. 42
Streptococcus Intermedius ..................... 33 Shigella Dysenteriae ................................ 42
Group C and D infections ........................ 33 Yersinia Enterocolitica............................. 43
Streptococci Viridans .............................. 33 Yersinia Pseudotuberculosis: .................. 43
Yersinia Pestis ......................................... 43 Mycoplasma Pneumoniae ....................... 52

Helicobacter Pylori .................................. 44 Mycoplasma/Ureaplasma ....................... 52
Campylobacter Jejuni .............................. 44 Chlamydia Trachomatis ........................... 52
Bacteroides Fragilis ................................. 44 Chlamydia Psittaci ................................... 53
Coccobacilli (pleomorphic).......................... 45 Chlamydia Pneumoniae .......................... 53
Haemophilus Influenza ........................... 45 Rickettsia................................................. 53
Haemophilus Ducreyi .............................. 45 Orientia Tsutsugamushi .................... 54
Aggregatibacter ...................................... 45 Coxiella Brunetti...................................... 54
Legionella Pneumophila .......................... 46 Erhlichia & Anaplasma ............................ 55
Bordetella Pertussis ................................ 46 Bacterial Vaginosis .................................. 55
Brucella ................................................... 46 Viruses: 56
Bartonella ............................................... 47 Anti-Viral Drugs: 56
Kingella Kingae ........................................ 47 Acyclovir...................................................... 56
Francisella Tularensis .............................. 48 Valacyclovir ............................................. 56
Pasteurella Multocida ............................. 48 Ganciclovir .................................................. 56
Cardiobacterium Hominis ....................... 48 Valganciclovir .......................................... 56
The "Other" Bacteria: 49 Penciclovir................................................... 57
Acid-Fast ..................................................... 49 Famciclovir .............................................. 57
Mycobacterium Tuberculosis .................. 49 Cidofovir ..................................................... 57
Mycobacterium Leprae ........................... 49 Foscarnet .................................................... 57
Mycobacterium Avium Intracellular Interferons .................................................. 57
Compex (MAI) ......................................... 49 Lamivudine ................................................. 57
Mycobacterium Kansasii ......................... 49 Ribavirin ...................................................... 57
Spirochetes ................................................. 50 Imiquimod................................................... 57
Treponema Pallidum ............................... 50 Amantadine/Rimantadine........................... 58
Treponema Pertenue .............................. 50 Olsteltamivir/Zanamivir .............................. 58
Treponema Pallidum Endmicum ............. 50 Anti-RetroVirals: 58
Treponema Carateum ............................. 50 Nucleoside Reverse Transcriptase Inhibitors
Borellia .................................................... 50 (NRTI's)........................................................ 58
STARI- Southern Tick Ass. Rash Illness .... 51 Abacavir .................................................. 58
Leptospira Interogans ............................. 51 Didanosine .............................................. 58
Non-Gram Staining ..................................... 52 Zidovudine .............................................. 58
Lamivudine.............................................. 58 Inclusion Bodies: ..................................... 61

Stavudine ................................................ 58 DNA Virus Overview: ................................... 62
Zalcitab.................................................... 58 RNA Virus Overview: ................................... 63
Tenofovir................................................. 58 Vaccine Notes: 64
Emtricitabine........................................... 58 Recombinant Viral Protein Vaccines ........... 64
Nonnucleoside and Nucleotide Reverse Live Attenuated Vaccines ............................ 64
Transcriptase Inhibitors (NNRTI's) .............. 58 Killed Virus Vaccines ................................... 64
Nevirapine............................................... 58 Pooled Gamma Globulins............................ 64
Efavirenz ................................................. 58 DNA Viruses: 65
Delvaridine .............................................. 59 Naked DNA Viruses: 65
Tenofovir................................................. 59 Adenoviridae:.............................................. 65
Protease Inhibitors (PIs) .............................. 59 Parvoviridae: ............................................... 65
Saquinavir ............................................... 59 Erythema Infectiosum ............................. 65
Indinavir .................................................. 59 Polyomaviridae / Papillomaviridae ............. 66
Ritonavir.................................................. 59 HPV- Human Papillomaviruses ................ 66
Nelfinavir ................................................ 59 Enveloped DNA Viruses: 67
Amprenavir ............................................. 59 Hepadnaviridae: .......................................... 67
Fosamprenavir ........................................ 59 Herpesviridae: ............................................. 67
Tipranivir ................................................. 59 Replication (Ex: HSV) ............................... 67
Darunavir ................................................ 59 Herpes Simplex Virus (HSV) 1 & 2 ........... 67
Atazanavir ............................................... 59 Varicella (VZV)..................................... 68
Fusion Inhibitors (entry inh) ........................ 59 Epstein-Barr Virus ................................... 69
Enfuvertide ............................................. 59 Herpesviridae Lymphocryptovirus:
CCR5 Antagonists (entry inh) ...................... 59 Herpesvirus 4 ....................................... 69
Maraviroc (selzentry) .............................. 59 CMV ........................................................ 69
Integrase Inhibitors ..................................... 59 HHV's ...................................................... 70
Raltegravir (Isentress) ............................. 59 Poxviridae: .................................................. 70
Antiretroviral Combo's to AVOID ................ 60 Molluscum Contagiosum ........................ 70
HAART ......................................................... 60 Small Pox ................................................. 70
Virus Overview ................................................................................................................................
RNA Viruses: ............................................................................
61
A Quick Rundown........................................ 61 Positive Sense RNA ..................................................................
The big picture: ....................................... 61 Calciviridae.................................................. 73
Noroviruses (Norwalk Virus) ................... 73 Pneumovirus (F) ...................................... 81

Hepatitis E Virus ...................................... 73 Rhabdoviridae ............................................. 81
Coronaviridae ............................................. 73 Lyssavirus- Rabies Virus .......................... 81
Coronavirus ............................................. 73 Ambi-Sense RNA Viruses ..........................................................
Flaviviridae .................................................. 74 Arenaviridae................................................ 83
Flavivirus: ................................................ 74 Lymphocytic Choriomeningitis Virus (OW)
Hepatitis C Virus: ..................................... 74 ................................................................ 83
Picornoviridae ............................................. 74 Lassa Fever Virus (OW) ........................... 83
Enteroviruses (acid stable) ...................... 75 Tacaribe Complex (NW) .......................... 83
Hepatitis A Virus ..................................... 75 Double-Stranded RNA Viruses ..................................................
Coxsackieviruses ..................................... 75 Reoviridae ................................................... 83
ECHOViruses: .......................................... 75 Orthoreovirus ......................................... 83
Poliovirus ................................................ 75 Orbovirus (arbovirus) .............................. 83
Rhinoviruses............................................ 76 Coltivirus (Arbovirus) .............................. 84
Retroviridae ................................................ 76 Rotavirus ................................................. 84
HIV (and LAV)→ ...................................... 76 Viroid-like Agents ....................................................................
Togaviridae ................................................. 77 Hepatitis D Virus ......................................... 84
Alphaviruses............................................ 77 Prions and Slow Viruses ...........................................................
Rubivirus- Rubella ................................... 78 Subacute Sclerosing Panencephalitis Virus . 84
Astroviridae ................................................ 78 JC Virus (PML) ............................................ 84

Animal Lentiviruses ..................................... 84
Negative Sense RNA ......................................................................................................................... 79
Bunyaviridae ............................................... 79 Prions (PrP) ................................................. 84
California Serogroup ............................... 79 Scrapie: ................................................... 84
Orthobunyavirus ..................................... 79 Kuru ........................................................ 85
Deltavirus (Unclassed) ................................ 79 Creutzfeld-Jakob Dz: ............................... 85
Filoviridae ................................................... 79 Other Spongiform encephalopathies: ..... 85
Marburg virus and Ebolavirus: ................ 79 Recap on Hepatitis viruses: ......................................................
Orthomyxoviridae ....................................... 79 Hepatitis A Virus ..................................... 86
Influenza- A, B, C ..................................... 80 Hepatitis B Virus ...................................... 86
Paramyxoviridae ......................................... 80 Hepatitis C Virus ...................................... 86
Morbilliviruses (H,F) ................................ 80 Hepatitis D Virus ..................................... 86
Paramyxovirus (HN, F)............................. 81 Hepatitis E Virus ...................................... 86
Mycology- more than yeast infections ?............................................................................................

Superficial Fungal Infections ....................... 92 87
Anti-Fungal Agents:..........................................................................................................................
Pityriasis Versicolor ................................. 92 87
Amphotericin B Deoxycholate .................... 87 Tinea Nigra: ............................................. 92
Lipid formulations ................................... 87 Superficial Hair Infections: .......................... 92
5-Flucytosine............................................... 87 Black Piedra: ........................................... 92
-Azoles ........................................................ 87 White Piedra: .......................................... 92
Ketoconazole .......................................... 87 Cutaneous Mycoses .................................... 92
Fluconazole ............................................. 87 Dermatophytes of hair: ........................... 93
Itraconazole ............................................ 88 Dermatophytes of skin: ........................... 93
Voriconazole ........................................... 88 Dermatophytes of Nails .......................... 93
Posaconazole (triazole) ............................... 88 Subcutaneous Mycoses............................... 93
Caspofungin Acetate ................................... 88 Chloroblastomycosis ............................... 93
Griseofulvin ................................................. 88 Phaeohyphomycosis (Subcut fungal
Terbinafine.................................................. 88 infection) ................................................. 93
Oral Thrush and Topicals: ........................... 89 Parasitology- Quick and dirty ...................................................
Nystatin................................................... 89 AntiParasitic Agents .................................................................
Clotrimazole ............................................ 89 Anti-Malarials.............................................. 94
Ampho B suspension............................... 89 Chloroquine ............................................ 94
Topicals: .................................................. 89 Primaquine.............................................. 94
Systemic Mycoses: ...................................... 89 Quinine ................................................... 94

Quinidine ................................................ 94
Systemic Mycoses ............................................................................................................................ 90
Histoplasmosis ........................................ 90 Mefloquine ............................................. 94
Blastomycosis ......................................... 90 Pyrimethamine ....................................... 94
Coccidiomycosis ...................................... 90 Prophylaxis and Treatment ..................... 95
Paracoccidiomycoses .............................. 90 Anti-Giardials .............................................. 95
Opportunistic Mycoses: .............................. 91 Metronidazole......................................... 95
Candida Albicans ..................................... 91 Furazoladine ........................................... 95
Aspergillus Fumigatus ............................. 91 Amebicidic Agents ...................................... 95
Cryptococcus Neoformans ...................... 91 Iodoquinol ............................................... 95
Mucor and Rhizopus (sp) ........................ 91 Paromomycin .......................................... 95
Pneucystis Jiroveci .................................. 91 Metronidazole......................................... 95
Sporotrichis Schenkii ............................... 91 Other Anti-Protzoals ................................... 95
Leshmaniasis ........................................... 95 Trichomonas Vaginalis ............................ 98

Trypanosomiasis ..................................... 95 Nematodes: ................................................ 99
Toxoplasmosis......................................... 95 Enterobius Vermicularis (Pinworms) ....... 99
Anti-Helminthics ......................................... 95 Ascaris Lumbricoides (Roundworm)....... 99
Mebendazole .......................................... 95 Trichinella Spiralis (Whipworm) .............. 99
Ivermectin ............................................... 95 Strongyloides Stercoralis (Threadworm) . 99
Pyrantel Pamoate.................................... 96 Ancylostoma Duodenale/Necator
Thiabendazole ......................................... 96 Americanus (Hookworms)....................... 99
Anti-Trematodes ......................................... 96 Dracunculus Medinensis ......................... 99
Praziquantel ............................................ 96 Onchocerca Volvulus............................... 99
Anti-Cestodes .............................................. 96 Loa Loa .................................................... 99
Quick Tx overview: ...................................... 96 Wuchereria Bancrofty ............................. 99

Toxocara Canis ........................................ 99
The Parasites ................................................................................................................................... 97
Protozoa (GI): .............................................. 97 Cestodes (Tapeworms) ............................... 99
Giardia Lamblia ....................................... 97 Taenia Solium (Pork Tapeworm) ............. 99
Entamoeba Histolytica ............................ 97 Taenia Saginata (Beef Tapeworm) ........ 100
Cryptosporidium ..................................... 97 Diphyllobothrium Latum (Fish Tapeworm)

.............................................................. 100
Protozoa (CNS) ............................................ 97
Dypylidium Caninum ............................. 100
Toxoplasma Gondii ................................. 97
Echinococcus Granulosus ...................... 100
Naegleria Fowleria .................................. 97
Trematodes (Flukes) ................................. 100
Trypanosoma Gambiense/Trypanosoma
Rhodesiense ............................................ 97 Schistosoma .......................................... 100
Protozoa (Visceral) ...................................... 97 Clonorchis Sinensis................................ 100
Trypanosoma Cruzi ................................. 97 Paragonimus Westermani ..................... 100
Leishmania Donovani .............................. 98 Systems Overview....................................................................
Protozoa (Hematologic) .............................. 98 Nervous System Infections: ...................... 101
Malaria: ................................................... 98 Cardiovascular System Infections: ............ 102
Plasmodium Vivax/Ovale ........................ 98 Gastrointestinal System Infections: .......... 103
Plasmodium Falciparum .......................... 98 Respiratory Infections: .............................. 104
Plasmodium Malariae ............................. 98 Urinary Tract Infections: ........................... 105
Babesia.................................................... 98 Genital tract Infections: ............................ 105
Protozoa (STD's) .......................................... 98 Male: ..................................................... 105
Female: ................................................. 105 Viral STI's ............................................... 106

Both: ..................................................... 105 Skin/Muscle/Bone Infections: ................... 107
Sexually Transmitted Diseases: ............. 105 Other infections with Cutaneous Symptoms
Pelvic inflammatory Dz ......................... 106 .................................................................. 108
STI syndromes and symptoms .............. 106
Bacteria
Bacteria Overview:
General Terminology/Basics:
Cell- Membrane: Capsule:
 Site of electron transport, oxidative phosphorylation, and  Well-defined polysaccharide structure surrounding cell-
chemoreceptors. external to wall
 Carrier lipids, enzymes, PCP (PCN-binding proteins).  Bacillus anthracis exception→ poly-D-glutamic acid
Mesosomes: Surface Proteins:
 Convoluted invagination of plasma membrane→ septal and  Anti-phagocytic proteins in wall of some gram-positives→
non-septal forms ( function is involved in replication and cell may serve as adhesins that ↑ colinization
division). Glycocalyx→ SLIME LAYER
Plasmids:  Loose network of polysacc fibrils, synthesized by surface
 Mini-chromosomes. enzymes, that surround some bacterial cell walls
Ribosome: 70s in Bacteria  Adhesive properties w/ prominent antigenic (Ag) sites
Transposon: Appendages:
 Mobile gene that jumps from site to site on a chromosome,  Flagella : H
plasmid, or between the two.  Fxn in locomotion and contain Ag determinants
Peptidoglycan  Pili: (fimbriae)
 a.k.a→ Murein or mucopeptide .  Constructed of pilin protein
 Present in all cell walls BUT mycoplasma.  Ordinary Types (adhesins): Bacterial adherence and G+
 Complex polymer- Backbone of N-acetylglucosamine(NAG) cell conjugation
and N-acetylmuramic acid (NMA) with tetrapeptide side  Sex Pilus: attach donor and recipient bacteria in G- cell
chains. conjugation
 Tetrapeptide→ L-Ala, D-Isoglutamine, L-Lysine (Or  Note: may confer antiphagocytic properties- M-protein
DAP) and D-ala of S. Pyogenes
 Tetrapeptide side chains often cross-bridge with adjacent Endospores
NMA's  For survival of nutr deprivation→ metabolically inactive and
 May contain diaminopimelic acid (unique to prok's cell walls) heat resistant (d/t calcium dipicolinate)
 *** β-1,4 glycosidic bonds b/n NMA and NAG are cleaved by  Germinate in more favorable conditions
LYSOZYME***  ** Bacillus and Clostridium are main players in this guide**
 ***Peptidoglycan is site of action for penicillins (PCNs) and Biolfilms:
Cephalosporins (CPN's)***  Aggregates of cells that ↑ nutrient uptake and often exclude
 Muramyl Dipeptide→ adjuvant, pyrogen, somnagen, antimicrobials***
mitogen Growth→ b = a * 2n (b= # cells at given time, a= # starting cells, n=
# divisions (n= t/g, time/generations)
Important Enzymes/Metabolic Pathways:

Carbohydrate/Energy metabolism
Glycolytic Pathway- Substrate level phosphorylation
Gluc + 2NAD + 4ADP + 4Pi→ 2 pyruvate + 2 NADH + 4ATP + 2H+
TCA cycle
Pyruvate + 3NAD + FAD + CoA + GDP + Pi → Acetyl-Coa + 2CO2 + 3NADH + 1 FADH2 + 1GTP
Oxidative Pathways
Pyruvate + NADH → Lactate + NAD (Strepto)
Pyruvate (via pyruvate decarboxylase)→ CO2 + Acetaldehyde → Ethanol (yeast)
Electron Transport
NADH + O2 + ADP + Pi → NAD + H20 + ATP
Nitrogen
Nitrogen fixation: N2→ NH3
Ammonia Assimilation: NH3→ amino acids
High NH3→ glutamate dehydrogenase Pathway ( a-ketoglut + NH3 + NADPH + H → L-Glutamate + NADP + H20) -No ATP req
Low NH3→ 2 step
1. Glutamate Synthetase (ET→Need ATP)→ L-glutamate + NH3 + ATP→ L-glutamine + ADP + Pi
2. Glutamate synthase reaction→ a-ketoglutarate + L-glutamine + NADH + H+→ 2L-glutamate + NADP+
Transamination→ glutamate + a-keto acid → a-ketoglutarate + Amino acid
Oxygen:
Enzymes and Reactive Oxygen species
*Superoxide dismutase: 2O2-A + 2H+ →O2 + H2O2
*Catalase: 2H2O2→ 2H2O + O2
Peroxidase (replaces catalase in some microbes): NADH + H+ + H2O→ NAD+ + 2H2O
Some aerotolerant anaerobes may use Mn2+ as an ROS scavenger
Other Nutrients:
Glucose→ uptake via PEP: Sugar Phosphotransferase System (PTS)
Iron→ Siderophores (neisseria have receptors for human siderophore transferrin)- 2 types: Enterbactin (enterochelin) and Hydroxamate
DNA Replication and Enzymes:

Supercoiling:
Neg ST if >10.6bp/turn, Positive ST if <10.6bp/turn
Class I Enzymes: Topoisomerase I (omega protein)→ relax pos & neg DNA by breaking 1 strand of helix without ATP
Class II topoisomerases: DNA Gyrase→ introduce negative coils via ATP (Breaks BOTH strands)
DNA gyrase→ gyrA and gyrB
gyrA→ nicking and sealing activity is inhibited by nalidixic acid and other quinolines
gyrB→ binds ATP- inh by novobiocin and coumermycin (coumermycin to toxic for clinical use)
DNA Polymerase I: 3 fxns
1.Synthetic Activity: Bind 3' of Okazaki fragment and adds dNTPs until reaches 5' end of adjacent OFragment
2. Nick Translocation activity: 5'→3' exonuclease to remove RNA primer and fill emptied streth
3. Proofreading: 3'→5' exonuclease for mismatched pairs
DNA Polymerase II→
5'→3' polymerase and 3'→5' exonuclease
DNA Polymerase III→
1. 5'→3' DNA-dep DNA polymerase: adds long stretched as a time
2. 3'→5' exonuclease→ Proofreading like DNA pol I
***HAS NO 5'→3' exonuclease function!
RNA Synthesis:
rRNA→ 23S, 16S, 5S subunits→ 30S (16s + 21s- transl init) and 50s  Tetracycline: block binding of charges tRNA's to acceptor
(23s + 5s+ 32prots - transpeptidase) site
RNA pol: always 5'→3' synthesis  Chloramphenicol: binds peptidyltransferase and blocks its
Terminations: reaction
 rho-independant: hairpin loop + UUUUUUUUUUUU→ RNA  Erythromycin: blocks translocation
pol holoenzyme senses loop and terminates Transcription control:
 rho-dependant→ hairpin loop only (rho-factor binds) Negative control always involves a REPRESSOR PROTEIN
tRNA→ 4 loops (1- tRNA synthetase recognition, 2- anticodon  Negative inducible→ ligand inactivates repressor
loop, 3- extra loop, 4- pseudouracil loop to recognize ribosome)  Negative repressible→ ligant activates repressor
Initiation via S-D sequence Positive Control always involves an ACTIVATOR PROTEIN
RNA synthesis and antibiotics:  Positive inducible→ ligand activates activator protein
 Streptomycin (AG's): block assembly of 70s ribosome  Positive repressible→ ligand inactivates activator protein
Exotoxins:
See individual Bacteria for the best descriptons. This list isn't all inclusive.
Alteration of cellular components

Bug Toxin Gene location MoA
Staphylococcus α-Toxin Bacterial Chromosome Pore forming toxin
Streptococcus Pyogenes Streptolysin O Bacterial Chromosome Pore forming toxin
Clostridium Perfringens α-Toxin Bact chrom and plasmid Disrupts membranes
Pseudomonas Aeruginosa Type III Cytotoxin Phage Cytoskeletal changes
Salmonella spp Type III Cytotoxin Bacterial Chromosome Alters actin cytoskeleton
Superantigens
Staphylococcus Aureus TSST-1 Bacterial Chromosome Release of cytokines
Staphylococcus Aureus Enterotoxins Phage Release of cytokines
Streptococcus Pyogenes Erythrogenic Toxins A-C Phage Release of cytokines
Inhibition of protein synthesis

Corynebacterium Diphtheria Diphtheria Toxin Phage ADP ribosylates EF-2
Pseudomonas Exotoxin A Bacterial Chromosome ADP ribosylates EF-2
Shigella Dysenteriae Shiga Toxin Plasmid Inactivates 60S ribosome
EH E. Coli Vero Toxin Bact Chrom and Phage Inactivates 60S Ribosome
Increased synthesis of cAMP

Vibreo Cholera Cholera Toxin Bacterial Chromosome Turns ON stimulatory G protein
E. Coli (ET-spp) ST Toxin Plasmid Turns ON stimulatory G protein
Bacillus Anthracis Anthrax Toxin Plasmid Adenylate Cyclase activity
Bordetella Pertussis Pertussis toxin Bacterial Chromosome Turns OFF inhibitory G protein
Altered Nerve Impulse Transmission

Clostridium Tetani Tetanus Toxin Plasmid Inhibits inhibitory neurotransmitter release
Clostridium Botulinum Botulinum Toxin Phage Inhibits acetylcholine release of NMJ
Taxonomy:
Gram Stain:
Procedure:
1. Crystal violet
2. Iodine
3. Alcohol decolorization
4. Safranin Colorstain
Gram Negative Cell Wall: RED/PINK Gram Positive Cell Wall: PURPLE
 Lysozyme Resistant  Lysozyme Sensitive
 Peptidoglycan (2-10% of wall)  Peptidoglycan (50% dry weight of wall)
 Lipoprotein  Teichoic and Teichuronic Acids- water soluble polymers →
 Crosslinks peptidoglycan (peptide bond) and outer serve as antigenic determinants
membrane (non-covalently inserted)  Chemically bonded to peptidoglycan
 Lipopolysaccharide (endotoxin)  Lipoteichoic Acid in membranes of bonded to
 While this is associated mainly with Gram Negative membrane glycolipid (particularly mesosomes)-
cells, It is also found in the membrane of the G+ anchors wall to membrane
bacillus, Listeria  Polysaccharides
 Outer Membrane
 Phospholipid bilayer→Contains lipopolysaccharide
(Endotoxin) that replace phospholipids on outer
surface
 Contains Porins, OMP's
 Lipopolysaccharide- ↑ IL-1, TNF when released, may
activate complement and coag cascade
 Structure→ O-antigen (serotyping), Core
polysaccharide and Lipid A (TOXIN COMPONENT)
 Braun Lipoprotein→ anchors outmembrane to
peptidoglycan
 Periplasmic Space→ b/n cell membrane and outer
membrane
 Hydrated peptidoglycan, specific carrier molecules,
Oligosaccharides
 Hydrolytic Enzymes→ Beta-Lactamase
Acid-Fast Staining:
Stain for Mycobacteria/Nocardia- Acid fast= RED (ALL other bacteria are NON-ACID FAST and stain BLUE)
Special stain req'd d/t mycolic acids in cell wall (a-subbed B-hydroxy fatty acids)
Cord factor→ disaccharide trehalose sub'd with mycolic acids→ inhibits leukocyte migration
Nocardia- may stain either way in clusters from slide to slide
Parasitic Oocytes are acid fast for Cryptosporidium, Cyclospora, Isospora
Selective Growth Media/Cultures

Special Media: Uses: Notes:
Blood agar Differentiate Hemolysis α (green/incomplete); β (clear/total); ƴ (red/no hemolysis)
Chocolate Agar H. Flu and Gonococcus Both non-hemolytic but require free Hb
Bordet-Gengou/Regan Lowe Agar Bordetella Pertussis
Thiosulfate-Citrate-bile salts sucrose agar Vibrio Cholera Alkaline media
Buffered Charcoal year extract agar Legionella Contains iron and cysteine
Lowenstein-Jenson Agar Mycobacterium Contains egg-yolk lipids to aid growth- replaced by broth
Thayer-Martin/New York City Agar Selective for gonococcus Chocolate Agar w/ Abx to eliminate competing flora
MacConkey's Agar Citrobacter Lactose-Fermenting enterics
Klebsiella macConKEE'S Agar
E.Coli and Enterobacter
Serratia
Antimicrobials:
General Principles:
Just some quick key points of review:
 Antagonism: Most cidal drugs require active cells to work- adding a static Abx leads to ↓ fx
 Post-Antibiotic Effect: Persistant effect of an antimicrobial on bacterial growth following a brief exposure (AG's and FQ's)
 Concentration Dependant Killing: Killing depends on peak concentration (then PAE continues)→ AG's and FQ's
 Time Dependant Concentration: Killing depends on amount of time above a the MIC of a drug (PCN's, Cephalosporins)
Bug Hints
*Remainder of this page thanks to Dr. Allman's e-mail notes- GO TO ALL OF HIS LECTURES
Will be referred to from the individual drug sections.
Gram+ Bugs Gram Negatives:- Fence bugs (PEK)
 Staph Aureus May or may not be widely resistant
 Strep  Proteus
 Enterococcus  Escherichia Coli
Atypicals (No cell wall)  Klebsiela
 Chlamydia Gram Negatives- SPACE Bugs
 Mycoplasma Aliens bugs with multi-drug-resistances common
 Legionella  Serratia
Anaerobes  Pseudomonas
 Peptostreptococcus (Pharynx)  Acinetobacter
 Bacteroides (Belly/Stomach)  Citrobacter
 Clostridium (Colon)  Enterbacter
Gram Negatives- Piddly Bugs
Typically low levels of resistance
 Haemophilus (H. Flu)
 Moraxella (M. Cat)
 Salmonella
 Shigella
 Morganella
 Neisseria (May show some resistance)
 Providencia (May show some resistance)
SPACE Bug treatment:

Box plus one Coverage with an Ace in the hole (and maybe the kitchen sink).
"Box" Drugs "Ace" in the hole
 Penicillins (Pipercillin/Ticercillin)  Aztreonam (PCN Allergy)
 Cephalosporins (Ceftazidime/Cefipime) Kitchen Sink
 Carbapenems (Imipenem/Meropenem/Doripenem)  Colistin
"Plus One" Drugs
 Aminoglycosides (Gentamycin, Tobramycin, Amikacin)
 Fluoroquinolones (Ciprofloxacin, Levofloxacin)
Anaerobe Coverage
Clindamycin, metronidazole, Augmentin, unasyn, timentin, zosyn, cefotetan/cefoxitin, Moxifloxacin, Erta/Mero/Imipenen
Atypical Coverage
Quinolones (moxi,cipro, Gema, Levo), TCNs (Doxy/Tetra), Macrolides (Erythro/Clarithro/Azithro)
Enterococcus Coverage:
Ampicillin, Amoxicillin, Unasyn, Pipercillin/Zosyn, Vancomycin, Linezolid, Quinopristin/Dalfopristin, Daptomycin, Nitrofurantoin (UTI)
Overview of antimicrobial MoA's:
 Peptidoglycan Cross-linking inhibitors (block cell wall  Block DNA topoisomerases
synthesis)  Fluoroquinolones
 Penicillins, Cephalosporins, Imipenem, Aztreonam  Block mRNA synthesis
 Peptidoglycan Synthesis inhibitors  Rifampin
 Bacitracin, Vancomycin  Block protein synthesis at 50s Ribosome Subunit
 Disrupt Bacterial Cell Membranes  Chloramphenicol, macrolides, clindamycin,
 Polymixins streptogramins, linezolid, lincomycin
 Block Nuceotide Synthesis  Block protein synthesis at 30s Ribosome Subunit
 Sulfonamides, Trimethoprim  Aminoglycosides, Tetracyclines
Bacteriostatics:
 ECSTaTiC to be bacteriostatic
 Erythromycin, Clindamycin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol
Bacteriocidals:
 Very Finely Proficient At Cell Murder
 Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole
Mechanisms of Resistance
1. Drug Inactivation
 Penicillins, Cephalosporins, Aminoglycosides, Tetracyclines, Spectinomycin, Chloramphenicol, Erithromycin
2. Target Site Mutation
 Cycloserine, Bacitracin, Cephalosporins, Carbapenems, Vancomycin, Aminoglycosides, Tetraclycines, Spectinomycin
 Chloramphenicol, Erithromycin, Clindamycin, Linezolid, Quinolones, Rifampin, Metronidazole, Sulfonamides
 Dapsone, Isoniazid, Ethambutol
3. Decreased Drug Uptake
 Cephalosporins, Carbapenems, Vancomycin, Aminoglycosides, Tetracyclines, Chloramphenicol, Erythromycin
 Clindamycin, Sulfonamides
4. Increased Drug Efflux
 tetraclycines, Erythromycin, Quinolones
5. New Plasmid Coded enzyme
 Sulfonamides, Trimethoprim
Bug-Drugs:
Penicillins
 "House and Garage" basic structure
 MoA: β-Lactam antibiotics target PCN-Binding Proteins (PBP's)
 inhibits Peptidoglycan Transpeptidase and blocks peptidoglycan cross-linking
 Insoluble in lipids→ poor dist to brain, CSF, or prostate unless inflamed
 Elim: RENAL excretion #1; Biliary Excretion w/ ampicillin, nafcillin and the anti-pseudomonals
 ADRs:
 Hypersensitivty: #1 ADR→ all PCN's equal in allergic rxn potential (Immediate- IgE- or Delayed-IgM/IgG)→ Mac pap rash #1 rxn
 Hematologic (eosinophilia, thrombocytopenia, neutropenia)
 Interstitial Nephritis
 Pseudomembranous Colitis
Penicillin G Carboxy Penicillins
(Procaine Pen g; Benzathine Penicillin)→ ACID LABILE (Pen VK for (Ticarcillin*/ Carbenicillin)→ ↑ perm to cell walls
oral admin)  Covers:
 Watch lytes→ K+ and Na+ salts  Streptococcus; PEK Bugs; ***Pseudomonas***;
 Covers→ Streptococcus and some enterococcus Enterobacter
 Staph=99% resistance; Pneumococcus resistant in some  Carbenicillin (stable oral form- high urine concentrations,
areas body cannot tolerate Tx dose for systemic infections)
Aminopenicillins  Ticarcillin ( 2-4x more active than Carb vs Pseudomonas;
(Ampicillin/AmOxicillin) HIGH sodium load)
 Amino acid group→ ↑ penetration of G- walls  ADRs: Hypersens; Carboxy- dose dep plt dysfxn; Na+
 Covers: Overload
 Streptococcus/Enterococcus Penicillinase resistant Penicillins
 Haemophilus, Proteus Mirabilis, E. Coli, Klebsiella (antistaph PCN's)→ Meth, Naf, Ox, Clox, Diclox
 ADR→ Diarrhea: Amp>Amox (take with food)  Covers Strep AND b-lactamase positive Staph
Uriedopenicillins  IV→ Meth; Ox, Naf- hepatic elim
(Pipercillin)  PO→ Clox and diclox
 Covers (Step; Enterococcus; PEK bugs; SPACE bugs)  HIGHER rate of interstitial nephritis
*B-lactamase inhibitors→ Clavulonic Acid, Sulbactam, Tazobactam
Cephalosporins
 Thiazolide and B-Lactam Rings in structure
 MoA: same as penicillins
 Gen ↑→↑ G- coverage: NO CEPHALOSPORIN covers enterococcus, Legionella, Mycoplasma, Chlamydia
 TAN-FOX Anaerobe coverage
 Kinetics:
 Oral admin→ prodrug esters (Cefuroxime axetil; Cefpodoxime Proxetil)
 Renal excretion for most; Hepatic Elim for cefoperazone and ceftriaxone
 3rd gens→ penetrate BBB well (↑ if meninges is inflamed
 ADRs:
 Hypersensitivity: 5-15% cross react w/ PCN allergy
 Hematologic: Bleeding ass/w methylthiotetrazole side-chain (cefamandole; cefoperazone; cefpodoxime)
 Causes hypoprothrombinemia d/t blocking vitamin K epoxide reductase
 Diarrhea: ↑ with biliar excreted drugs; Pseudomembranous colitis rare
 RARE interstitial Nephritis
 Disulfiram-like intolerance w/ Alcohol: Cefamandole, cefoperazone, cefotetan, moxalactam (NMTT-side chain)
 Immuno→ Serum sickness-like illness in children (F/M/N)- Cefaclor
 Drug-Drugs:
 Anticoags: (warfarin) potentiate Fx
 Alcohol: disulfiram-like rxn
 Probenecid: Prolongs excretion in cephalosporins w/ tubular excretion
Third Generation
First generation  Oral: Cefixime, Cefopodoxime; Parenteral: Ceftriaxone**,
 Oral: Cephalexin; Parenteral: Cefazolin cefotaxime
 Covers: Staph/Step; Minimal G-; NO ANAEROBES  Covers→ Strep; SACE
 Antipseudomonal Cephalosporin→ Poor G+ coverage, but
Second Generation good SPACE coverage ← Ceftazidime, Cefoperazone
 Cefuroxine (oral or parenteral preps)→ covers Staph/Strep;
H. Flu/M. Cat/E. Coli; PEK bugs Fourth Generation
 2nd gen Cephamycins→ Cefoxitin/Cefotetan → adds  Cefepime (Parenteral)
coverahe of anaerobes  Covers→ Staph/strep again; SPACE bug coverage; NO
anaerobes
Aztreonam (a monobactam)
 RARELY has cross reaction w/ PCN allergy
 ADRs: Hematologic (anemia, Leukopenia, Thrombocytopenia)
 Covers: Gram Negatives (SPACE bugs)
 Tx for :
 serious nosocomial infections of multiple organisms
 Community Acquired Pneumonias w/ risk factors for pseudomonas (bronchiectasis)
 Hospital Aquired Pneumonias w/ severe PCN allergy; late onset; MDR organism
Carbapenems
Imipenem, Meropenem, Doripenem
 PharmacoKinetics:
 MoA: Bind PBP-1 and PBP-2 in susceptible bugs and is CIDAL
 Imipenem: Renal metab by brush border enzyme dehydropeptidase-1 (which is inhibited by cilastin- longer lastin' w/ cilastin)
 ADRs:
 Imipenem: Seizures (in pts w/ epilepsy or if not dose-adjusted in renal failure)
 5-15% cross rxn w/ PCN allergy
 Imi/Mero/
 Hematologic→ anemia, leukopenia, thrombocytopenia
 Covers: G+; G-; Anaerobes→ Tx of serious nosocomial infections by multiple bugs
 Doripenem: covers SPACE bugs and Anaerobes
 Ertapenem: NO ENTEROCOCCUS coverage; once daily
Vancomycin
 Glycopeptide derived from Streptomyces Orientalis (1950's)→ recent ↑ of use d/t MRSA
 MoA: Inh biosynth of peptidoglycan polymers during cell wall formation (D-ala-D-ala)
 also injures protoblasts by altering cytoplasmic membrane
 Kinetics:
 Abs: Poor abs from GI (Give IV unless for C. Diff infxn)
 Dist: Enter CSF if inflammation
 Excr: excreted unchanged via glom filt
 Elderly; Renal Dz; Cachexia
 Desired peak- 20-40; Trough- 10-20)
 ADRs:
 nephrotoxic (trough conc); Ototoxic (Peak conc)
 Local rxns: RED-MAN Syndrome (flushing and hypotension- too much too fast- px w/ antihistamine); Thromboplebitis
 May produce a neuromuscular blockage
 Covers: Gram Positives ONLY (Staph/Strep/Enterococcus/Clostridium/B. Anthracis/Corynebacterium)
 Only use if properly indicated to AVOID CREATING RESISTANT STRAINS
Aminoglycosides
Gentamicin, Tobramicin, Amikacin, Streptomicin, Neomycin, Paromomycin
 Abx for serious gram-negative bugs
 MoA: Cidal
 Bind outer membrane of cell→ Rearrange LPS
 ATP-dep uptake→ becomes irrev trapped in cytoplasm→ binds **30s** and 50s Ribosome subunits→ ↓ prot synth
 PAE and Concentration dep killing
 Kinetics:
 Abs: Poor abs from GI
 Distr: Concentrations in lungs are 25-50% of those in serum
 Excretion: Unchanged via glom filtration
 Elderly; Renal Dz; Cachexia
 ADRs: Thrombophebitis; Nephrotoxiticty (Trough >2ug/mL); Ototoxicity (peak); NM blockade (Tx w/ IV calcium)
 Covers:
 Staph only through syngery (add a PCN)
 Gram negatives: Piddly bugs, PEK bugs, SPACE bugs (INCLUDING PSEUDOMONAS)
 Indicated:
 Genta/Tobra/Amikacin→ bacteremia, Pneumonias, intra-ab infxn, skin/soft tissue
 Streptomycin→ TB
 Gentamicin (±TCN or Chloramphenicol)→ Severe brucellosis
 Orals Neomycin→ surgical Px of intest flora; Hepatic coma to ↓ NH3-forming intestinal bacteria
 Oral Paromomycin→ Intestinal Amebiasis; tapeworms
 topicals→ ear, eye, skin infections
Quinupristin/Dalfopristin
 Streptogrammin antiobiotic→ irreversibly bind 50s ribosomal subunit (static alone, cidal combined)
 Quin→ inh peptide chain formation via early termination
 Dalfo→ ing peptide chain elongation via interference w/ peptidyl transferase
 Coverage:
 Vanc-resistance enterococcus faecalis; PCN-Resistant pneumococcus; MRSA
 Some anaerobes, and some G- (H. Flu)
 ADRs: Infusion site reaction if thru peripheral line (PICC/Central line preferred)
Linezolid
 Oxazolidinone class→ inh protein synth via binding 23s subunit of 50s Ribosome subunit
 100% bioavailable orally
 Covers: MRSA, PCN-Resistant Step Pneumo; VRE; VISA
 ADRs: Thrombocytopenia (esp if Tx >2wks)
 Drug-Drug: ****MAOI's**** and SSRI→ serotonin storm
Mupirocin (Bactroban)
Nasal Abx for MRSA carriers
Tetracyclines:
TCN, Chlortetracycline, OxyTCN, Demeclocycline, Methacycline, Doxycycline, Minocycline
DO NOT USE IF <8yo
 MoA: Binds 30s Ribosomal subunit→ static  Drug-Drugs:
 Kinetics:  Divalent/Trivalent Cations: Ca/Mg/Zn/Al/Fe (Chelates
 Doxy/Mino→ 90-100% oral Abs→ Hepatobiliary elim and ↓ absorption)-
(long half life)  Anticoagulants→ potentiates anticoagulant fx
 TCN/OxyTCN/Demeclocycline→ 60-75% oral abs→  Bactericidal agents→ ↓ FX
Renal Excretion (6-17hr half-life)  Covers: Gram Positive; Gram Neg (H. Flu/Neisseria),
 ADRs: ATYPICALS, RICKETTSIA→ GOOD FOR INTRACELLULAR
 GI; hypersensitivity; Candidal superinfection ORGANISMS (DOXY)
 Photosensitivity (severe but ↓ w/ doxy/mino)  Uses:
 Tooth discoloration/Bone deposition in children under  Rickettsia/Mycoplasma Pneumoniae/Most Chlamydia
8 (including fetus) (doxy)
 Demclocycline (DInsipidous- USED TO TREAT SIADH)  Acne (propionibacterium); H. Pylori infection
 Minocycline→ Ance, Vestibular FX  Brucellosis (a TCN + gentamicin); Cholera and
(dizzi/ataxia/vertigo); skin/mucus membrane Vulnificus; Borrellia Burgdorferi
pigmentation  ***SIADH→ Demeclocycline
 Fanconi like syndrome
 (N/V/L/polydips/uria/proteinuria/acidosis/hypok
alemia)
 OUTDATED TCN********** esp if contains citric
acid
Macrolides
Erythromycin, Clarithromycin, Azythromicin
 MoA: Reverisbly binds 50s ribosomeal subunit→ STATIC  Cholestatic Hepatitis (AVOID ESTOLATE IN
 Kinetics: PREGNANCY)→ N/V/D then Jaundice, F, ↑ LFT's
 Abs: Erythro (base/Stearate/ethylsuccinate complete  Clarithro/Azithro
abs in fasting state- ESTOLATE NOT EFFECTED BY  Much less GI fx; HA, Dizziness; Allergic reactions
FOOD)  Drug-Drug:
 Distr: ALL dist longer into tissues > blodd  Erythro/Clarithro:
 High conc in alveolar MQ's and leukocytes vs  Erithro→ interfere w/ CYP450 and metabs form
Extracellular Fluids inactive complex w/ CYP450
 Azithro→ Tissue = 10-100x serum  ↓ metabolism of theophylline, Warfarin,
 Metab/Excretion: Carbamazepine, Cyclosporine
 Erithro/Clatithro: Hepatic Metabl- 1.4h halflife  Azithro: No P450 effects
 Clarithro: Metab in liver via oxidation and  Coverage:
hydrolysis→ 20-30% unchanged in urine  Erythromycin
 Azithro: Elim in feces via hepatic excretion; half  Staph/Strep; M. Cat/H. Flu (poorly); C. Jejeni;
life = 68hrs Atypicals
 ADRs:  Clarithromycin
 Erythro:  Staph/Strep; M. Cat/H. Flu; C. Jejuni; Atypicals,
 cramps; N/V/D; IV→thrombophlebitis; Allergic MIA complex; H. Pyrlori
reactions;  Azithromycin
 Same as clarithro
 Use in: PCN allergies, Mycoplasma Pneumoniae, Legionairres, Trachomatis (even during preg- just not erythro estolate)
Clindamycin
 lincomycin→ mod'd to ↑ potency and absorption
 MoA→ binds 50s Ribosomal subunit→ inh protein synthesis
 Kinetics:
 90% bioavailable (food ↓ rate but not extent)→ good tissue dist → metab via liver
 Coverage: G+ and anaerobes

 Strep; Staph (limited rate vs b-lactams); anaerobes (bacteroides/ C. perfringens/ Peptostreptococci/peptococci)
 ADRs: Allergic Rxns; Diarrhea in 20% (↑ in oral prep); C. Diff #1 culprit; Hepatoxic (mild and Severe)
Chloramphenicol
 Reversibly binds 50s subunit of 70s ribosome
 Kinetics:
 Suspension→ must be hydrolyzed in intestines to activate chloramphenicol
 IV form→ incomplete hydrolysis (IV~70% of oral therapy)
 EXCELLENT CSF penetrance (30-50% w/i inflam)
 Metab via glucuronidation in the liver (wide variations in metab and excretion in kids- keep serum b/n 10-30ug/mL)
 Covers:
 G+; G-; Aerobes and Anaerobes→ Rickettsia and Chlamydia
 ADRs: (why its not often used in US***)
 Hematologic: Reversible bone marrow depression d/t direct fx → inh of mitochondrial protein synthesis
 Anemia, leukopenia, thrombocytopenia
 ***Idiosyncratic Aplastic Anemia***
 Majority= wks-mos after completion of therapy (can be dose-independant)
 Possibly ↑'d incidence of childhood leukemia
 Gray-Baby Syndrome***
 Abdo distention, Vomiting, Cyanosis, Circulatory Collapse
 neonates have ↓↓ ability to conjugate chloramphenicol and to excrete active forms in the urine
 Assoc/w concentrations >50ug/mL
 Uses: Bacterial Meningitis (H. Flu; Strep Pneumo; N. Meningitidis) if PCN/Ceph allergy AND Rickettsia infections
Sulfonamides
 Structurally similar to PABA (para-aminobenzoic acid) - precursor req'd by bacteria for folate synthesis→ STATIC
 MoA:
 Bacterial cell walls are impermeable to folate→ MUST SYNTHESIZE FROM PABA
 Sulfonamides compete w/ PABA for dihydropteroate synthetase (starves cell of tetrahydrofolate)
 **Sulfonamides may have ↑ affinity for enzyme than PABA**
 Excretion→ Glomerular filtration
 ADRs:
 Anaphylaxis
 Cutaneous rxns: Morbilliform Rash; SJS; Erythema Multiforme; Photosensitivity
 Nephrotoxicity: Crystalluria w/ less soluble compounds- sulfadiazine/sulfathiazole (admin w/ fluids)
 kernicterus: If admin'd in LAST MONTH OF PREGNANCY
 Coverage:
 G-POS: Straph; Strep; Bacillis Anthracis
 G-Negs: H. Flu/ Providencia/ Salmonella/ Shigella/; PEK bugs; CE bugs (citrobacter and Enterobacter)
 Other: Nocardia Asteroides; Chlamydia Trachomatis; Toxoplasma Gondii; Plasmodium Falciparum
 indications: Acute uncomplicated UTI, Pneumocystis Carinii (Tx and Px); Nocardiosis; Toxoplamsa (malaria); Rheumatic Fever Px
Trimethoprim
 MoA: nonsulfonamide pyrimidine→ INHIBITS Dihydrofolate Reductase→ ↓ bacterial tetrahydrofolate synth (CIDAL OR STATIC)
 Excretion: 80% unchanged via glom filtration and tubular secretion
 ADRs:  G-Neg: PEK; SCE bugs
 Cutaneous (#1): Pruritis; Rash (Serratia/Citrobacter/Enterobacter)
 GI: N/V/D; ↑ serum transaminases and serum  Other: Pneumocystis Carinii
 Coverage:  Indications: Acute Uncomp UTI; Px for Recurrent UTI;
 G-POS: Staph/Strep/Anthrax Traveler's Diarrhea
TMP-SMX
 Syngergistically combines (CIDAL)
 Indications:
 UTI: uncomplicated; recurrent; Acute/Chronic Prostatitis
 Resp Tract Infections: Acute exacerbations of chronic bronchitis; Pneumonoa; Otitis Media, Sinusitis; PNEUMOCYSTIS CARINII (Px/Tx)
 GI: Shigellosis, Salmonella, Traveller's Diarrhea; Cholera
 STDs: Uncomplicated gonococcal infections, Chancroid
 Others:
 Malaria, Nocardiosis, Brucellosis, Osteomyelitis, Stenotrophamonas Maltophilia
 Bacteremia, Meningitis, Toxoplasmosis (Tx/Px), Px in neutropenics
 Drug-Drugs:
 Warfarin: may potentiate anticoag Fx (MONITOR INR)- Best to use something else!
 Methotrexate: Sulfonamides can displace methotraxate from Protein binding sites→ ↑ [methotrexate]
Nitrofurantoin
 MoA: Unclear- possibly interferes w/ bacterial carbohydrate metabolism via INH of Acetyl-CoA or creates 5-nitro anion (free rads)
 Kinetics:
 Distribution: Serum and tissue concentrations VERY VERY LOW→ Urine concentration VERY HIGH
 Excretion: Linear rate; related to CrCl (↓ efficacy is GFR impaired) DO NOT USE IF GFR <40-50mL/min
 ADRs:
 **Pulmonary reactions**:
 Acute rxn: Hypersens (Eosinophilia); LL infiltrate; F, C
 Subacute rxn: after 1 month Tx→ C/Dyspnea/Intersitial infiltrate (often reversible; May not be)
 Chronic Rxn: After 6 months Tx→
 GI Reactions: N/V/D
 Peripheral Neuropathy w/ renal insufficiency!!!
 Coverage:
 G-POS: Staph Aureus (MRSA); Staph Saprophyticus; Enterococcus Faecalis (VRE) and Faecium
 G-Neg: E. Coli; Klebsiella Pneumonia; Citrobacter spp; Enterobacter Aerogenes
 Indications: Acute Uncomplicated UTI and UTI prophylaxis
Methenamine
 MoA: No direct antibacterial effect→ in urine (pH <5.5) → hydrolyzed to formaldehyde (CIDAL via protein denaturing)
 ADRs:
 Hypersensitivity (Rash/Pruritis)
 Hemorrhagic Cystitis
 GI (N/V/D)
 AVOID IN HEPATIC INSUFFICIENCY→ Ammonia byproduct
 RENAL FAILURE→ Acid forms could lead to systemic acidosis
 Coverage:
 All bacteria/Fungi (All susceptible to formaldehyde)
 Certain Urea+ Bacteria (protease) can alkalize urine and ↓ effectiveness
 [Formaldehyde] affected by
 [methenamine]
 rate of hydrolysis of methenamine to formaldehyde
 Rate of Urine Loss from bladder (voiding or drainage)→ ↑ urine output→ ↓ Fx via ↓ concentration and exposure time
 Indications: Px of UTI (NOT FOR Tx of ACUTE UTI)
Quinolones
Ciprofloxacin, Ofloxacin, Levofloxacin, Moxifloxacin, Gemifloxacin
DO NOT USE IF <18yo
 Structurally related to nalidixic acid→ all BUT nalidixic acid have been fluorinated (↓ susceptibilty to resistance)
 MoA: CIDAL
 target DNA gyrase (inh supercoiling of DNA) and promote cleavage of DNA w/n enzyme-DNA complex
 Kinetics:
 Abs: food ↓ abs rate but NOT extent; Mg/Al/Ca→ bind and ↓ oral bioavailability (which varies by agent)
 Cipro: 3.2hr HFLF; 70% bioav; 29% renal excretion
 Ofloxacin: 5.0 HFLF; >95% bioav; 73% renal excretion
 Levofloxacin: 6.7hr HFLF; 100% bioav; 61-86% renal excretion
 Moxifloxacin: 6-7hr HFLF; 90% bioax; 15-21% renal exc
 Gemifloxacin: 7hr HFLF; 70% bioav; 36% renal excretion
 Drug-Drug:
 Theophylline: ↓ theophylline metab (cipro can double lvls; Levo has no documented Fx)
 Antacids/Iron/Sucralfate: Interfere w/ abs of FQ's
 Warfarin: ↑ anticoag effects (via metab or protein binding changes) - Levoflox shows no doc'd Fx
 ADRs:
 Hypersenstivity: mac-pap rash, urticaria, pruritis, Anaphylaxis/angioedemia, PHOTOSENSITIVITY
 GI Rxn: Abnormal LFT's; D/N/V
 Nephrotoxicity: rare
 CNS: HA/Dizziness
 Musculoskeletal: Artheropathy (↑ if <18yo); TENDON RUPTURE
 ↑ rates of ADR if <18; >60; or on concomitant steroid therapy
 Coverage:
 Cipro: Excellent G-NEG coverage
 Levo/Gemi/Moxi: G-POS and G-NEG coverage
 G-POS:
 Strep pneumo; Strep Pyogenes; GBS (Agalactiae); Staph Aureus; Enterococcus Faecalis (????)
 G-NEG:
 Salmonella; Shigella; N. Gonorrhoeae; H. Flu; M. Cat; Morganella Morganii;
 PEK bugs
 PE (of SPACE) bugs
 Indications:
 Chlamydia/Gonorrhoeae (PID)
 mild-mod resp infections
 Prostatitis
 Gastroenteritis/Infectious Diarrhea
 Skin infxns
 Cipro/Oflox: Only use in DM or if G-NEG orgs are suspected (and in combo w/ newer agents)
 Levo/Gemi/Moxi→ better gram -POS coverage
 Moxi→ covers anaerobes well
 Bone/Joiny: Cipro/Ofloxo
 Complicated intra-ab infections: Cipro/Metronidazole or Moxifloxacin monotherapy
 Specifics:
 Cipro: MOST POTENT FQ vs G-Neg's (at least 4x more potent vs pseudomonas)→ oral if possible
 Lelvo/Gemi/Moxifloxacin: Oral if possible d/t ↑ bioavailability
 G+ coverage (including resistant S. pneumo)
 G- Coverage (less potent than cipro)
 Atypical respiratory bugs (Mycoplasma/Chlamydia/Legionella)
 Moxi for Anaerobes***
Rifampin
 TB→ RIPE or RIPS treatment
 First line Tx for TB (CIDAL)→ 2nd line for px
 MoA: Inhibits DNA-dependant RNA polymerase (supp init of chain formation in RNA synthesis)
 Reserved for TB but active vs G+ and G- bacterua (
 Synergy when combined/w INH→ shorter course of Tx
 Kinetics:
 Dist: Wide dist in many tissues (CNS, Abscesses, IC sites)
 Metab: Primarily metab'd via deacetylation in liver (Autoinduction of metabolism→ max @ 6th dose)
 ↑ Cyp450 enzymes→ Warfarin, Theophylline, Narcotics, oral hypoglycemics, Steroids (OC's)
 ADRs:
 Hepatoxic (rare)→ transient ↑ in serum transaminases (Risks→ ↑alcoholics w/ pre-existing liver Dz and ↑↑↑ in RIF+INH)
 GI Upset (VERY COMMON)
 Hypersensitivity (Flushing, Fever, Pruritis, Systemic Flu-like syndrome, THROMBOCYTOPENIA)
 Bodily Fluid Discoloration (ORANGE EVERYTHING→ stain contact lenses/clothes)
Isoniazid (INH)
 MoA: Inhibits synthesis of mycolic acid → active t-port into cell
 Active killing of cells in EC environment and Inhibits growth of ones dormant in MQ's and caseating granulomas
 Kinetics:
 Metab: Primarily via acetylation
 Monoacetyl Hydrazine (important metab)→ Resp for hepatotoxic fx
 Excr unchanged in urine or further acetyl'd to diacetyl or hydrodroxylated to an electrophilic intermediate
 Rates of acetylation of INH and monoacetyl hydrazine→ dep on phenotype of pt (Rapid or Slow)
 Slow→ higher blood concentrations and ↑ risk of ADR w/ chronic therapy
 Elim: rate dep on acetylator phenotype→ 1-2hrs for rapid and 2-5hr halflife for slow
 ADR's:
 Transient ↑ in serum transaminases (first 8-12wks)
 Hepatotoxic (Risks= Age, pre-existing lvr disease, 4-8wks of Tx)
 NeuroTox (Prevent with pyridoxine (vitamine B6) => Risks ↑ with alcoholics, children, malnourished, slow acetylators
 Hypersensitivity
 Therapy:
 Tx of TB, and Px for +PPD
Pyrazinamide (PZA)
 MoA: unknown→ Cidal towards dormant organisms in acidic environment in MQ's
 Kinetics:
 Metab: Hydrolyzed in liver to active pyrazinoic acid
 Elim: 5-hydroxypyrazinoic acid→ excretion from kidneys (half life in 9-10hrs)
 ADRs:
 Hepatotoxic (↑ incidence w/ higher doses)→ monitor function and closely watch for hepatitis
 Hyperuricemia (↓ renal excretion of uric acid)→ BAD FOR GOUT
 GI UPSET
 Hypersensitivity: photosensitivity/ Rash
Ethambutol
 TB line of treatment: Static→ MoA unknown
 Elimination: 60-80% parent compound + inactive metabolite excreted in urine
 ADRs:
 OPTIC NEURITIS
 ↓ vis acuity and red-green color blindness→ usually reversible (time dependance on degree of impairment
 Incidence is dose dependant→ monitor acuity and color perception q4-6 wks
 MONITOR CLOSELY IN KIDS
Rifabutin
 2nd line for TB (Rifamycin derivative)
 Reserved for pts w/ bad rifampin ADRs or exp rifampin intolerance
 More effective than Rifampin vs MAC→ Px and Tx of MAC
 ADRs:
 NEUTROPENIA, HEPATOTOXIC, Rash, GI sxs, Arthralgis, myalgias, discolored urine/sweat/tears
Rifapentine
 Once weekly w/ INH in the continuation phase of SPECIFIED TB treatment (HIV-negative and NON-Cavitary pulmonary TB)
 ADR's similar to Rifampin
Clofazamine
 Most widely used ANTI-LEPROSY agents
 MoA: Preferentially bind mycobacterial DNA→ inh's transcription
 ADR:
 GI upset; Severe and lifethreatening abdomen pain d/t crystal deposition
 DISCOLORS skin and eyes
Dapsone
 Mycobacterium Leprae Treatment: DR C (Combo Tx due to rapid dev of resistance)
 MoA: Comp inh of folic acid synthesis (inh dihydropteroate synthase)→ STATIC
 Rapid and Complete absorption from GI tract→ Drug of choice when sensitive
 ADRs→
 Dose-Dependant hemolytic anemia: Hypersensitivity Reaction (Sulfone Syndrome- 1-4wks in Tx→ F/M/Dermatitis, Jaundice)
 Tx -steroids
Contrindicated in Pregnancy:
SAFE Moms Take Really Good Care
 S→ Sulfonamides→ Kernicterus
 A→Aminoglycosides→ ototoxicity
 F→ Fluoruquinolones→ Cartilage Damage (wait till kids 18+)
 E→ Erithromycin → Acute Cholestatic Hepatitis (clarithromycin is Embryotoxic)
 M→ Metronidazole is mutagenic
 T→ tetracyclines→ Discolor teeth, inhibit bone growth
 R→ Ribaviren→ teratogenic
 G→ Griseofulven→ Teratogenic
 C→ Chloramphenicol→ Grey Baby
Mnemonics
Bugs w/ IgA protease:
 "SHiN"→ Steptococcus Pneumoniae, Haemophilus Influenza B, Neisseria spp
Bugs w/ Capsules
 "Kapsules Shield SHiN"→ Klebsiella Pneumoniae, Salmonella, Steptococcus Pneumoniae, Haemophilus Influenza B, Neisseria spp
 Capsules give + quellung reaction→ Quellung= Swellung of the capsule
Intracellular Bugs:
 Obligate ICs: "stay inside when its Really Cold"→ Rickettsia and Chlamydia
 Facultative IC's: "Some Nasty Bugs May Live Longer Facultatively"
 Salmonella, Neisseria, Brucella, Mycobacterium, Listeria, Legionella, Francisella
Obligate Aerobes:
 " Nasty Pests Must Breath"
 Nocardia, Pseudomonas, Mycobacterium TB, Bacillus
Obligate Anaerobes:
 "Can't Breath Air"→ Clostridium, Bacteroides, Actinomyces
Urease Positives:
 "Particular Kinds Have Urease"→Proteus, Klebsiella, H. Pyrlori, Ureaplasmia
Lysogenic Phage Toxics:
 "ABCDE's of phage toxins"→ ShigA-like toxin, Botulinum Toxin, Cholera Toxin, Diphtheria Toxin, Erythrogenix Toxic (S. Pyogenes)
Gram Positive Cocci
 Staph→ NO StRESS→ Novobiocin Saprophyticus Resistance, Epidermidis Sensitive
Staph Diff:
 CAtalase before COagulase in the dictionary→ All staph have CAtalas; Only Staph aureus has Coagulase
Neisseria:
 MeninGococcus ferments Maltose AND Glucose→ Gonococcus only ferments Glucose
Pseudomonal infections:
 PSEUDOMOnas
 Pneumonia (esp CF), Sepsis (black skin lesions), External otitis (swimmers ear)
 Diabetic Osteomyelitis, Malignant Otits externa in DM
Enterobacteriaceae: (Oxidase Negative)
 SSPEEKS→ Salmonella, Serratia, Proteus, E. Coli, Enterobacter, Klebsiella, Shigella
 All drink COFFEE→ Capsulsar (K), O Antigen, Flagella (H antigen), Ferment Glucose, Endotoxic (O-Antigen), Enterobacteriaceae
Salmonella vs. Shigella:
 Salmonella have Flagella, Shigella just propella's itself w/ actin polymerization
Zoonoses:
 "Big Bad BUgs From Your Pet Emu"
 Bartonella→ Cat Scratch Fever→ bacilliary angiomatosis in imm-comp'd
 Borrelia burgdorferi→ Lyme Dz→ Ixodes tick
 BrUcella→ Undulent fever from Unpasteurized dairy
 Fransicella Tularensis→ Tularemia→ Tick bites and Francis the rabbit
 Yersinia Pestis→ Plague→ flea bites, rodents, *prairie dogs*
 Pasteurella multocida→ Cellulitis following animal bite
Classification Overview:
Not necessarily complete- but many common ones
Gram Positive Bugs:

Cocci Bacilli
Catalase Positive:  Spore Forming
 Coagulase Positive  Aerobes
 Staphylococcus Aureus  Motile
 Coagulase Negative  Bacillus Cereus
 Novobiocin Sensitive  Non-Motile
 Staphylococcus Epidermidis  Bacillus Anthracis
 Novobiocin Resistant  Obligate Anaerobes
 Staphylococcus Saprophyticus  Motile
Catalase Negative:  Clostridium Tetani
 β-Hemolytic  Clostridium Botulinum
 Bacitracin Sensitive  Clostridium Difficilie
 Streptococcus Pyogenes  Non-Motile
 Bacitracin Resistance  Clostridium Perfringens
 Streptococcus Agalactiae  Non-Spore Forming
 α,β, or ƴ -Hemolytic  Motile
 Grows in 40% Bile (Group D)  Listeria Monocytogenes
 Grows in 6.5% NaCl  Non-Motile
 Enterococcus Faecalis  Corynebacterium Diphtheria
 Does NOT grow in 6.5% NaCl
 Streptococcus Bovis Beaded Filaments
 α-Hemolytic  Non-Acid-Fast, Obligate Anaerobe
 Bile-Esculin Negative  Actinomyces Israelii
 Optochin Susceptible  Weakly Acid-Fast, Obligate Aerobe
 Streptococcus Pneumoniae  Nocardia Asteroides
 Optochin Resistant  Nocardia Brasiliensis
 Streptococcus Mutans
 Streptococcus Intermedius
Gram Negative Bugs:

Diplococci
 Oxidizes Glucose and Maltose Coccobacilli (pleomorphic)
 Neisseria Meningitidis  X & V factors on chocolate agar
 Oxidizes Glucose only  Haemophilus Influenza
 Neisseria Gonorrhoeae  Growth on charcoal yeast agar with iron and cysteine
 Legionella Pneumophila
Bacilli  Growth on Bordet-Gengou Medium
 Lactose Fermenter (Fast Fermenters)  Bordetella Pertussis
 Indole Positive  Aerobic
 Escherischia Coli  Brucella
 Biochemical tests  Bartonella
 Klebsiella Pneumoniae  Requires Cysteine for growth
 Lactose Non-Fermenter  Francisella Tularensis
 Oxidase Positive  Oxidase + and Catalase +
 Pseudomonas Aeruginosa  Pasteurella Multocida
 Glucose Positive
 Vibrio Cholera
 Oxidase Negative
 Urease Positive
 Proteus Mirabilis
 Produce H2S and Motile
 Salmonella Typhi
 Salmonella Enteritidis
 No H2S and NON-motile
 Shigella Dysenteriae
 Motile @ 25C/Non-Motile @37C
 Yersinia Enterolitica
 Bipolar (paperclip) Staining
 Yersinia Pestis
 Curved, Small growth on Campy Agar
 Urease Positive
 Helicobacter Pylori
 Urease Negative
 Campylobacter Jejuni
 Strict Anaerobe
 Bacteroides Fragilis
The "Other" Bugs:

Acid-Fast
 Thing rods, Non-motile, Obligate Aerobes
 Mycobacterium Tuberculosis
 Grow at low temps and are Phenolase+
 Mycobacterium Leprae
Spirochetes
 Microaerophilic, and sensitive to high temperatures
 Treponema Pallidum
 Giemsa & Silver staining, Microaerophilic
 Borellia Burgdorferi
 Borrelia Recurrentis
 Aerobic, "Ice-Tong" appearence
 Leptospira Interrogans
Non-Gram Staining
 Mycoplasma Pneumoniae
 Chlamydia Psittaci
 Chlamydia Trachomatis
 Chlamydia Pneumoniae
 Rickettsia Rickettsii
 Rickettsia Prowazekii
 Coxiella Brunetti
Gram Positive Bacteria

Cocci
Catalase Positive:
 Coagulase Positive
 Staphylococcus Aureus
Staphylococcus Aureus
 Gram positive cocci in clusters
 Catalase +, Coagulase +, Gluc Ferm+→lactic acid, mannitol ferm+
 Yellow colony*: staphyloxanthin → inactivates ROS's and superoxides (↑ virulence)
 Techoic acid: Glycerol TA (SE), Ribitol TA (SA)
 Virulence Factors:
 Toxins: (Super Antigens marked as #######)
 Enterotoxins: preformed; strong IL-1 inducer; act on brain vomit center; inh intest water abs; act in 1-7hrs, no fever
 A- #1 food poisoning
 B- Rare- ass w/ staph enterocolitis
 C- Rare- ass w/ milk
 D- 2nd most common w/ food poisoning (±A); ass. w/ milk
 E- Rare, Assoc w/ milk
 TSST-1: toxic shock (tampons); nonfood
 Exfoliative Toxins (A and B)
 Other Factors:
 Staphyloxanthin
 Coagulase*: Clumping Factor; fibrinogen→fibrin→coats cell
 Protein A : Binds Fc region of Ig→↓ opsonization and phagocytosis
 Cytolytic Toxins: α, β, ƴ, δ, and P-V Leukocidin
 Panton-Valentine Leukocidin: PMN and MQ lysis→↑ resistance to phagocytosis
 Cause of necrotizing pneuomonia: erythroderma, airway bleed, leukopenia (MRSA)
 Hyaluronidase, Lipase
 MRSA: MecA gene on SCCmec
 Think Scott BAIO for #1's→Sepsis, Bacteremia, acute endocarditis, infective arthritis, osteomyelitis
 Ritter's Dz: Scalded skin syndrome (not bullous impetigo→ local infxn of scalded skin- Cx+/Nikolsky-, Phage group II, Exfol A)
 Exfol toxins→destroy IC cnxns of skin
 Perioral Erythema→Whole body w/n 2 days
 Nikolsky's sign→ large blister w/ clear fluid
 #1 cause of: Osteomyelitis, Infective Arthritis, Acute endocarditis, and Bactermia/Sepsis
 Tx→ Vancomycin/Cephalosporins/ topical bacitracin
Catalase Positive
 Coagulase Negative
 Novobiocin Sensitive
 Staphylococcus Epidermidis
 Novobiocin Resistant
 Staphylococcus Saprophyticus
Staphylococcus Epidermidis
 G+ clusters, Catalase +, Coagulase -, Novobiocin sensitive
 Glycocalyx (exopolysaccharide)= ↑ adhesion and Abx resistance, ↓ phagocytosis
 *****β-lactamase and Mutant Penicillin binding proteins→ PCN RESISTANCE in almost 100%!!!!!!*******
 Source/Transmission- Common to skin and transmitted through contaminated catheters or on artificial device implants
 Tx→ Vancomycin (most resist PCN/Cephalosprins)
 Prosthetic Valve Endocarditis→ <60 days think epidermidis; >60 days think Strep Viridans
Staphylococcus Saprophyticus
 Novobiocin resistance
 Virulence d/t ability to bind epithelium
 Almost entirely assoc/w UTI's→ dysuria, pyuria, and numerous organisms in urine
Catalase Negative:
 β-Hemolytic
 Bacitracin Sensitive
 Streptococcus Pyogenes
 Bacitracin Resistance
 Streptococcus Agalactiae
Streptococci:
Lancefield Grouping→ Ag carbohydrates A-S
Hemolyses also important→ α- Partial, β- COMPLETE, ƴ- No hemolysis
G+ cocci in chains and pairs
Facultative anaerobes or canophilic
NEED BLOOD ENRICHED MEDIUM FOR ISOLATION
Group A Streptococcus Pyogenes-

 G+, non-motile, fac anerobe, β-hemolytic
 Grouped by C-Carbohydrate, 80-M protein types
 Nutrition→ req blood/serum enriched media (hemolytic)
 Virulence factors:
 Hyaluronic Acid Capsule→ ↑phagocytosis resistance
 M Proteins→ degrades C3b, antiphagocytic
 F-protein binds fibronectin- est infxn, adhere to epith cells
 C5a-Peptidase→ ↓ compliment rxn
 Exotoxins:
 Pyrogenic Exotoxins: SpeA, SpeB, SpeC→ responsible for scarlet fever rash→ T-cell SUPERANTIGEN!!!
 Streptolysins S(oxygen stable- NONimmunogenic) and O (oxygen-labile- immunogenic- ASO test)
 Lyses leuks, plts, erythrocytes→ release lysosomal enzymes
 DNase→ A,B,C,D→ Depol's Free DNA (Anti-DNase B→ cutaneous GAS Marker)
 Streptokinase→ catalyzes activation of plasmin to lyse blood clots
 Infections:
 Skin→ if nephrogenic M-type→ post-strep Glomerulonephritis
 #1 cause of cellulitis!!!!!
 abcsesses, furuncles, carbuncles (hair follicle related); ↑ risk w/ Diabetes/Imm-supp/Skin break
 Tx- I&D abcsesses
 Impetigo: Contag. superficial infxn(2-5yo common ± S. Aureus)
 Non-bullous impetigo (vesiculopustules w/ crusting) pover/poor hyg/scabies; ±S.Aureus
 Pustular Impetigo: pus-fill vesicle→crusts (S.A. or GAS)
 Erysipelas→ always GAS, Upper derm/Lymph→ Sharp demarcation, edema, inflam, pain, systm signs
 Necrotizing Facitis→ flesh-eating- rapidly fatal gangrene (multi-organ failure)
 Scarlet Fever→ Red mac-pap rash (SAND-PAPER- and intense in skin folds); red/white strawberry tongue
 Pharyngitis→ If cardiogenic M-type→ Rheumatic Fever
 Non-suppurative infections- NO LIVE GAS
 AGN→ Ig immune complexes depositing in basement membrane→ facial edema and blood in urine
 Rheumatic Fever→ Anti-M Ab cross rxn w/ human cardiac tissue→ mig arth, subcut nodules, carditis and EM
 Tx→ PCN, (Oxacillin or vancomycin in mixed culture)
Streptococcus Agalactiae (Group B Step)

 CAMP positive(↑ b-hemolysis of S. Aureus), β-hemolytic, cocci in pairs
 Normal vaginal flora
 Virulence→ capsule and Sialic Acid (inhibits alt pway of complement)

 Infections:
 Neonatal sepsis, pneumonia and meningitis
 Meningitis- Early→ <7days, 60% fatals; Late→ 1wk-3mos, 20% fatal
 Post-partum endometritis
 Tx→ PCN w/ and AGs
 α,β, or ƴ -Hemolytic
 Grows in 40% Bile (Group D)
 Grows in 6.5% NaCl
 Enterococcus Faecalis
 Does NOT grow in 6.5% NaCl
 Streptococcus Bovis
Streptococcus Bovis (Group D)

 G+ pairs/Chains→ Catalase Negative, Grow in 40% bile but NOT in 6.5% NaCl
 Subacute Bacterial Endocarditis→ penetrates epith via lesion in colon→ aortic valve- adhering to plt-fibrin aggregates→ endocarditis
 Since it enters through GI Lesion- May signal colonic carcinoma or inflam bowel Dz
 Tx- PCN
Enterococcus Faecalis (Group D)

 #4 cause of nosocomial infections
 nonhemolytic, Grow in 6.5% NaCl, Tolerate 40% bile salt, Hydrolyze Esculin, Optochin resistant
 Local Infections→ UTIs, Biliary tract infections
 Systemic→ Subacute Bacterial Endocarditis (SBE)- IVDU
 In Gut, GU tract,
 Virulence:
 Agg Substance and Carbohydrate adhesins→ ↑ colonization
 Cytolysin→ inh G+ bacteria and induce local tissue damage
 Gelatinase
 ABX resistance→ AGs, B-lactams, vancomycin
 Tx→ Ampicillin or Vancomycin + AGs (Synergy) - CHECK RESISTANCE
 ALL Strains resistant to cephalosporins and some resistant to Vancomycin
 α-Hemolytic
 Bile-Esculin Negative
 Optochin Susceptible
 Streptococcus Pneumoniae
 Optochin Resistant
 Streptococcus Mutans
 Streptococcus Intermedius
Streptococcus Pneumoniae
 G+ cocci- pair or short chain, LANCET SHAPED  #1 Cause of MOPS→ M- meningitis, O-Otitis Media, P-
 CAMP NEGATIVE, Bile soluble, α-hemolysis in O2, β- Pneumonia, S- Sinusitis
hemolysis with NO O2  Pneumonia progression→Serous fluid in Alv→ Early
 Virulence: Consolidation (org/PMN)→ Late Conso (Cell Infiltrates)
 Capsule: → Resolution (clears)
 IgA protease: Px opsonization  Dx→ Gram Pos, Quellung Positive (↑ refractive mass d/t
 Adhesins: capsule), Bile sensitive and Optochin Sensitive
 Pneumolysin: Destroys ciliated epith cells  Tx→ PCN G, Vanco is PCN allergy; Px→ Polyvalent recomb
 Infections: vaccine for 60+yo
Streptococcus Mutans
 Major player in dental plaques→ secretes exopolysaccharides to glue itself to teeth forming plaques
 Optochin Resistant
Streptococcus Intermedius
 Inhabits GI tract→ microaerophilic bacteria thrive in low-O2 environs of brain/liver abscesses
 Optochin resistant
 Positive in blood culture often indicates the presence of abscesses
Group C and D infections

Non-rheumatic, but similar infections as GAS
Streptococci Viridans
Sub-acute endocarditis (#1) often following dental work→ central role in dental caries (Optochin Resistance- in mouth so not afraid Of the chin)
Viridis→ latin for green→ α-hemolytic strep
 Groupings:
 Anginosus→ S. Anginosus, S. Constellus, S. Entermedius
 Abscess in brain, oropharynx, peritoneal cavity
 Mitis→ S. Mitis, S. Pneumoniae, S. Oralis
 Subacute Bacterial Endocarditis, Neutropenic Sepsis, Pneumonia, Meningitis
 Mutans→ S. Mutans, S. Sobrinus
 Dental Caries, Endocarditis
 Salivarius→ S. Salivarius
 Bactermia, endocarditis
 Bovis→ S. Gallolyticus (subsp Gallolyticus and pasteurianus)
 Colon cancer (gallolyticus), Meningitis (pasteurianus)
 Ungrouped→ S. Suis
 Meningitis, Bacteremia, Streptococcal toxic shock syndrome
 Nutrient Variable Streptococci→ Abiotrophia Species
 Endocarditis, pancreatic abscess, otitis media, post-partum/abornal Sepsis
 Tx:
 PCN→ bacteriostatic
 MIC <0.1= sensitive; MIC 0.2-2mcg/ml= Mod Resistant (USE AG's), MIC >2mcg/mL= resistant (use AG's and for longer time frame)
Bacilli
 Spore Forming
 Aerobes
 Motile
 Bacillus Cereus
 Non-Motile
 Bacillus Anthracis
 Obligate Anaerobes
 Motile
 Clostridium Tetani
 Clostridium Botulinum
 Clostridium Difficilie
 Non-Motile
 Clostridium Perfringens
Bacillus Cereus
 G+ Rod, Spore-former, Motile, Aerobic,
 FOOD POISONING- Reheated rice!!!
 Spores
 Lecithinase (phospolipase C)
 Enterotoxins
 Necrotic Toxin→ Vasc permeability action
 Cereolysin→ Hemolysin- disrupts cholesterol of cell membrane
 Tx with fluid and lyte replacement
Bacillus Anthracis
 G+, Spore-former
 Capsule: D-glutamic Acid
 Three part Exotoxin:
 A- Edema Factor (EF) cya
 A- factor→ adenylate cyclase activated by calmodulin→ ↑IC cAMP-impaired flow of ions/water
 B- Lethal Factor (LF) lef
 A-Factor→ Protease that induces MQ's to prod high lvls of cytokines→ shock
 C- Protective Antigen (PA) pag
 B-Factor→ Promotes entry of EF into phagocytic cell
 Virulence factors: A-B binary toxins
 Edema factor(cya) + protective antigen (pag) → edema toxin
 lethal factor(lef) + protective antigen (pag) → lethal toxin
 Genomes/Plasmids:  Cutaneous Anthrax:
 Two virulence plasmids: pXO1 and pXO2  Most common
 pXO1→ lef-cya-pag controlled by atxA,atxR  Painless papule @ site of inoc→ ulcer w/ surr
 pXO2→ D-glutamate capsule gene: imm response vesicles→ necrotic eschar
is NOT protective  Germ→ rapid prolif→ Tox release→ localized
 atxA on pXO1 → ↑ acpA on pXO2 → ↑ capsule necrosis
gene expression → ↓ imm response  Round black lesion with rim of edema (malignant
effectiveness pustule)
 pXO2 only straings are just as virulent in animal  Diagnosis-
model  Papule material in microscope→ No spores but w/
 Infections: serpentine chain of bacilli
 Inhalational Anthrax: inh of spores  Culture: non-hemolytic, sticky colonies
 Mediastinal widening→ replication and local  Biochem confirm Dx
toxin release in lungs  Treatment:
 F, SoB, HA, V, chest/AbPain→ resp distress→  Inact cell-free vaccine vs PA→ short term
death w/n 3days  Live-attenuated vaccine
 60 day abx→ PCN, Ciprofloxacin, Doxycycline
Clostridium Tetani
 Large Spore-forming Cells (large terminal Spores)→ Drumsticks
 Toxins:
 Tetanolysin→ O2-labile hemolysin
 Tetanospasmin→ Non-conjugative Plasmid encoded heat labile neurotoxin: AB Toxin→A(light chain) is a zinc peptidase
 Released when cell lysed→ resp for paralysis
 Blocks synaptobrevin and prevent formation of vesicles and release of GABA and glycine
 Epidemiology:
 Reservoir in soil/and human/animal GI
 Trans via contam wounds or tissue injury
 Temporal pattern→ peak in summer/wet season
 NOT contagious
 Pathos:
 Inc→ 8-days(dep on distance from CNS)→ 3 forms (Local , cephalis (rare), and generalized (most common))
 Neonatal tetanus→ Ifxn of umbilical stump→ weakness an inable to suck→ spasm, rigid, opisthotonus→ dev delay (>90% mort)
 Localized→ Conf to musc @ infxn, painful and weak→ rigid, DTR are hyper, wks-mos then resolves
 Cephalic tetanus→ Primary infection is head, ↓ NM transmission of LCN's, Facial Palsy, dysphagia, extraoc paresis (Poor Prog)
 Generalized→ Prec by localized, Pres w/ lockjaw (Trismus). Risus Sardonicus, Drooling,, sweating , irritability
 Opisthotonus→ painful, generalized spasm→ can cause fractures and hemorrhage into muscle
 Worsens for 2wks then slow recovery
 Dx→ Presentations, Antitoxin neutralization in mice
 Tx→ Debride wounds, Metronidazole, Human tetanus Ig, Sxs Tx, Topical Abx to Umbilical stumbs
 if 3+ doses of vaccine→ nothing, if <3 or unknown→ Td vaccine in minor wound and TD vaccine and TIG for all other wounds
Clostridium Botulinum
 Large, G+ spore-forming rods, Fastidious and anaerobic
 7 Ag types→ Dz assoc/w A, B, E, F
 Toxin→ AB toxin with Zn endopeptidase activity→ Cleaves synaptobrevin, block vesicle formation and release of ACh
 Epid:
 Type A: West if MS River, Type B: Eastern US, Type C: Wet soil
 Foodborne Less than 30case/yr → most in home canned foods and some preserved fish
 A.B.E.F→ 1-3dys→ dizzy/weak→ blur vision, fix dil pupils, dry mouth, constipation, ab pain
 Bilateral descending weakness→ death from resp paralysis (5-10%)
 No MS changes→ recovery mos-yrs
 Infant botulism `100/yr→ honey/powdered formula
 A,B,F→ neurotoxin in infant GI under 1yr→ nonspec, wk cry, FtThrive→ flaccid paralysis
 Wound botulism is very rare→ Inhalation of toxin a bioterrorism concern
 A,B→ longer inc than foodborne,Almost exclusive assoc w/ black tar heroin injections (spores in heroin)
 Dx→ History, Toxin in food, serum, feces, etc→ Toxin assay perf on mice (heat @ 80 for 10m then culture)
 Tx→ supportive, trivalent antitoxin (A,B,E)
Clostridium Difficilie
 G+ Rod, Anaerobic, Spore-forming, Normal Flora of bowel , Pathogenic following Abx
 Toxins→ Work together or alone to produce Dz
 Enterotoxin (Toxin A)→ PMN Chemotactant and stim Cytokine release
 Cytopathic FX via disruption of tight cell-cell junction→ ↑ int wall perm and diarrhea
 Cytotoxin (Toxin B)→ Actin depolymerization and destr of cytoskeleton
 SLP→ allows binding of cells to intestinal epith (Infants lack SLP)
 Clinical (carrier state possible)
 Abx Assoc Diarrhea→ 3-21 days after starting Abx→ fever abdo pain and self limited
 Pseudomembranous colitis→ Cramping ab pain, Fever, Green/foul stools→blood diarrhea→ Fulminant colitis and perforation
 Toxic Megacolon→ Toxic dilation of small bowel→ May dev w/o preceding diarrhea
 Dx→ Toxins in stool samples, Endoscopy for urgent Dx→ red/raised circ yellow plaques- cobblestoning
 Tx→ d/c abx and follow with metronidazole or Vanc
Clostridium Perfringens
 G+, Spore-forming anaerobe, Spore intro via trauma, Produced alpha toxin- lecithinase
 Cause Gas gangrene, Soft tissue cellulitis, food poisoning
 Cellulitis→ crepitus (slow, painless, infection)
 Gas Gangrene→ Alpha toxin (lecithinase→ muscle cell necrosis) and Degradative enzymes (Crepitus)
 Enterotoxin→ enterotoxin inhibits glucose transport
 Enteritis Necroticans→ necrosis of small intestines from XS release of beta-toxin- 40% mort
 Non-Spore Forming
 Motile
 Listeria Monocytogenes
 Non-Motile
 Corynebacterium Diphtheria
Listeria Monocytogenes
 G+ coccobacillus, b-hemolysis and motile, Only G+ w/ LPS!!!!
 Unpasteurized cheeses and meats
 Flu-like to meningitis/encephalitis→ 20-30% higher mort than other foodborne illnesses→ ↑↑ Risk in PRegnant women!!!!!!!!
 May cause spont abortions, Intrauterine death, Premature delivery, or infxn of infant at birth (listeria neonate meningitis)
 Early Onset→ anemic, pneumonia, septicemia, 15-50% mort
 Late Onset→ Meningitis, Septicemia, 10-20% mort
 Internalins
 Listeriolysin O
 Actin-Based Motility (ActA surface protein)
 Monocyte Stimulants
 Two Phospholipase C Enzymes
 Tx→ PCN (Pneumoniae>Monocyogenes)
Corynebacterium Diphtheria
 G+, Non-motile club shaped rods, V and L shaped configurations
 Tox-negative strains are normal flora of URT
 Exotoxin→ Diphtheria toxin (AB)
 In bacteria lysogenized by bacteriophages carrying the tox-positive gene→ ADP-ribosylates EF-2 and shuts down protein synthesis
 Clinical→ Mild pharyngitis w/ F/C→ Spread up and down URT firmly adhering to mucosa
 Results in dirty, gray, pseudomembrane of fibrin, dead cells and Bacteria (Stays in Resp mucosa- no dissm)
 Toxin circulates→ hoarseness, stridor, myocarditis, cariotoxicity, soft palate paralysis,
 Neuropathy due to tropism for heart/nerves
 Cervical adenitis and edema- **Bull Neck**
 HOSTPITALIZE IMMEDIATELY
 Lab Dx→ gray/black colonies on tellurite containing differential medium; demonstrate diphtheria toxin by Elek test
 Tx w/ Abx and antitoxin→ Px w/ vaccine
Beaded Filaments
 Non-Acid-Fast, Obligate Anaerobe
 Actinomyces Israelii
Actinomyces Israelii
 G+ anaerobes, Branching rods, "Sulfur Granules", Contiguous growth thru anatomical barriers
 Cervicofacial, thoracic, and abdominal Lesions
 Weakly Acid-Fast, Obligate Aerobe

 Nocardia Asteroides
 Nocardia Brasiliensis
Nocardia Asteroides
 G+/ acid-fast filamentous aerobes, in soil and trans via inhalation of dust
 Dz sim to TB→ acute in children and imm-comp'd adults→ mets to brain
 Often no Dx until autopsy→ stains and culture
Nocardia Brasiliensis
Gram Negative Bacteria:

Diplococci
 Oxidizes Glucose and Maltose
 Neisseria Meningitidis
 Oxidizes Glucose only
 Neisseria Gonorrhoeae
Neisseria Meningitidis
 G- diplococci- Coffee Beans, Oxidizes Carbs, Best growth on chocolate agar
 Virulence Factor
 Capsule- basis for serotyping (13 types but most infxn by→ A, B, C, Y, W-135)
 Pili→ Adhere to nonciliated host cells and invade via endocytosis
 Porins:
 Por A and Por B (inh PMN Degran, aid in epith invasion,)- Por B PIA→ resist compl med-serum killing
 LOS- Lipooligosaccharide
 Lacks O-antigen of LPS; Lipid A is endotoxin (may release outer membrane blebs during replication)
 IgA protease- cleaves IgA Hinge
 Transferrin binding proteins- Binds human transferrin
 Pathos→
 Nasopharynx reservoir→ Inv Dz or Dev Ab and immunity
 Enter subepith via phagocytic vacuoles→ Bacteremia and progressively ill
 Ab's vs Capsule→ infants protected via maternal Ig, Complement system important defense
 ↑ risk if complement deficient in 3,5,6,7,8
 Epidemiology
 Endemic worldwide, Epidemic in dev'in countries
 Most Dz in US/Europe→ Serotypes B,C,Y; A and W-135 in dev'in countries
 highest rates in crowding populations→ transmit via resp droplets
 Infections
 Meningitis:
 HA/Meningeal signs/ Fever (F/V in younger)→ 100% mortality untreated and 10% treated
 Complications→ Hydrocephalus, Cranial nerve palsy, Cerebral edema, Cerebral infarct
 Meningococcemia
 H/o short URI, F, rash- Vascular collapse w/ DIC and small vess thrombi→ purpura and shock w/n hours of initial presentation
 SUSPECT IF petechiae and purpura in febrile child
 Severe shock/DIC→ Bil-Adrenal destruction→ Waterhouse-Friderichsen Syndrome
 Primary Meningococcal Pneumonia
 #1 manifestation in military recruits→ Y and w-135
 Dx- Micro→ N.M. in CSF (may confuse to S. Pneumo if over-decolorized)/ Cx→ *** CSF, Blood, Petechiae
 Tx→ PCN- vs Ceftriaxone- Px in close exposure
 Vaccines→ Group-spec Caps Polysaccharides→ A,C,Y, and W-135 (NOT B)→ rec @ 11-12
 Polysac- MPSV4- not T-cell/memory response and Conj MCV4- PS Cap cong w/ Diphtheria toxin→ T-cell and memory
Neisseria Gonorrhoeae
 Intracellular- G-Diplococcus→ Antigenic variations in pilin protein→ reinfections common (human Dz)
 Virulence:
 IgA1 protease; Adherence through pili and OMP's
 Pili→ phase variation (pilS and pilE loci)
 OMP's→ pI and PIII- porins and pII- clumping/opacity (pII→ promotes adherence and invasion→ septicemia)
 Attach to ciliated cells and induce ciliary stasis/ cell death and NG internalization
 Internalized NG rep in vacuoles and exit into subepith CT and then bloodstream
 LOS→ Lipo-Oligosaccharide→ Triggers TNFa (sialylation → ↑ resistance and common in DGI's)
 Sxs→
 Can cause pharyngitis and rectal infections
 Purulent discharge→ rectum/pharynx/Genital tract (male sxs= urethra/Fem asxs= vaginitis/urethritis/endocervicitis/salpingitis)
 DGI= disseminated infxn
 Septicemia→ skin and joint (1-3%: rash/mig arthralgia/supp arth)

 #1 purulent arthritis in adults
 Perihepatitis (Fitz-hugh-curtis synd)/ PID/ Pharyngitis/ anorectal/ Purulent conjunctivitis
 Ophthalmia Neonatorum→ blindness if not treated properly and immediately
 Dx:
 G stain and LM→ Poor sens
 Culture Thayer-Martin medium- PICKY EATER
 NAA→ High sens and spec→ urethra/endocerv/vaginal swab and urine (PCR/TMA) commercial kits available (±chlamydia)
 Tx:
 Uncomplicated→Ceftriaxone OR cefixime AND (Azithromycin or doxycycline)
 Dual infxn (chlamydia)→ Sxs of chlam after NG Tx→ inc longer and B-lactams useless for chlam→ test and treat for both
 Complicated: DGI→ Ceftriaxone/ Meningitis-endocarditis→ ceftriaxone/ Conjunctivitis→ IM ceftriaxon
Bacilli
 Lactose Fermenter (Fast Fermenters)
 Indole Positive
 Escherischia Coli
 Biochemical tests
 Klebsiella Pneumoniae
Escherischia Coli
 G- rod, Aerobe/Fac Anaerobe; Non-spore former, Catalase positive, Oxidase NEGATIVE, Lactose Fermenter
 MacConkey's Sorbitol Agar→ Sorbitol NON-fermener
 Serotypes: O- O-antigen of LPS, H- Flagella, K- Capsule Ag/ Virotype→ type of virulence or action
 Endotoxin
 Capsule
 Ag Phase Variation
 Type-III secretion System→ needle like system to inject toxin into cells
 Fe Sequestration factor
 Resistance to serum killing
o ABx resistance
 Tx→ Enteric pathogens treat symptomaticalls (Abx guided by susceptibility tests
 Infections→
 #1 cause UTI→ PAP Pili (P-fimbriae): bind D-gal-D-gal residue found in the P-blood group antigen
Virotypes
ETEC- Enterotoxigenic
 (Water Diarrhea in infants and Traveler's Diarrhea- no inflam or fever)
 Plasmid mediated, noninvasive- pedestal formation on LM
 Fimbral Adhesins→ CFA I and CFA II
 Enterotoxins→ LT (heat-labile) and ST (heat-stable)
o LT Toxin(sim to cholera toxin): AB5: B-Binds, A- ADP-ribosylates Gs→ Const activation of Adenylate cyclase and ↑ [cAMP]
o ST Toxin→ Stimulates guanylate cycles → ↑ [cGMP]
EPEC- Enteropathogenic
 (Infantile Diarrhea, some inflamm but no fever)
 Non-fimbrial Adhesion→ intimin
 NO LT or ST toxins→ DOES detroy microvilli though
 Bundle Forming Pilus (Bfp)
 Common in underdeveloped countries
EIEC- Enteroinvasive
 (Dysentery-like Diarrhea- mucus and blood- Severe Inflammation AND fever)
 Like Shigella!!!!! Non-fimbrial adhesions- possible through OMP
 INVASIVE!!!! Multi in epith cells→ entry is M-Cells
 Does not produce Shigella toxin
EAggEC- Enteroaggregative
 Persistant diarrhea in young children w/ immunization (NO FEVER)
 Fimbriae not characterized→ GVVPQ Fimbriae (NON-Invasive)
 Produces ST-Like Toxin and a hemolysin
EHEC- EnterHemorrhagic
 Pediatric Diarrhea (copious bloody discharge- hemorrhagic colitis, intense inflam and HUS)→ O157:H7
 Similar to EPEC, Mod Invasive
 Produces Shiga-Like Toxin→ Binds 60S ribosome and inhibits protein synthesis
 ***Abx Tx ↑ risk of HUS d/t prophage toxin release during lysis***
Klebsiella Pneuomoniae
 G- Rod, Fast/Lactose fermenter,→ Alcoholic "Current Jelly" pneumonia
 Frequently infects upper lobes of lungs, antiphagocytic capsule, Necrotizes and cavitates
 VERY DRUG RESISTANT!!!!!!
 UTI after Abx kills all competing bacteria, tract is complicated'
 Dx→ G- rods, Capsule→ mucoid colonies, and ferment lactose
 Tx is with a 3rd gen cephalosporin
Klebsiella Granulomatis
 Sexually Transmitted Inection
 G- rod- Granuloma inguinale/donovanosis→ Rare in US (india/Papaua NG/Carib/S. Africa (Diff to Cx)
 Similar to Syph chancre- painless/granulomatous and highly vascular (BEEFY)
 Dx→ donovan bodies in tissue sample (oval orgs in cytoplasm of mononuclear phagocytes or histiocytes)
 Tx→ Rec- doxycycline for 3 wks or till all healed
 Lactose Non-Fermenter
 Oxidase Positive
 Pseudomonas Aeruginosa
 Oxidase +, Catalase -, Urease -, Indole -
 Eikenella Corrodens
 Glucose Positive
 Vibrio Cholera
 Oxidase Negative
 Urease Positive
 Proteus Mirabilis
Pseudomonas Aeruginosa
 G- rod, Aerobic/Anaerobic, motile (pili/Flag), everywhere, Simple growth requirements, non-fermentor
 Pyoverdin- green pigment, Pyocyanin- blue pigment
 "Grape like odor" on skin infections
 Infects burn wounds, folliculitis (hot tubs/ whirlpools/swimming pools), 2º infxn in acne or leg depilation, fingernail infxn
 Ecthyma gangrenosa in neutropenic pts
 Major Pathogen for Cystic Fibrosis!!!!
 (Expresses biofilm phenotype in chronic infection- plus serum sensitive, rough LPS, low tox and mucoid)
 Biofilm→ Exopolysaccharide matrix surr community, 100-1000x ↑ abx resist
 Exotoxin A: Sim to Diphth Toxin→ ADP-ribosylates EF-II and inh prot synthesis
 Exoenzyme S : Req for dissm from burn wounds and tissue dest in chronic lung infections→ ADP-Ribates proteins (TIII Sec System)
 Elastase: Breaks down elastin, collagen, immunoglobulin, complement components
 Controlled by LadR transcription Factor- produced in presence of other PA Cells (Quorum sensing)
 Phospholipase C/Heat-Stable Phospholipase: Hydrolyse phospholipids→tissue damage
 Alkaline Phosphatase: Proteolysis→tissue damage
 Alginate: Promote adherence to resp epith cells, interfere with phagocytosis, may be imm-stimming
 LPS, Siderophores,
 Infections→
 Pneumonia, Osteomyelitis, Septicemia, Meningitis, Endocarditis, UTI, Panopthalmos, Malignant otitis externa, Burn wound infection
 Pseudomonas folliculitis: from immersion in cont hot tubs, whirl pools, swimming pools (2º to acne/depilate)
 Fingernail infections/Ecthyma Gangrenosa/Contact lens contamination
 Tx→ Resists multi-Abx (Tailor to sens)- Anti-PA PCNs→ Ticarcillin, Pipercillin plus AGs( Gentamicin or Amikacin)
Eikenella Corrodens
 Fastidious GNR, Facultative Anaerobe, Oxidase +, negative for catalase, urease, indole; Converts Nitrate to nitrite
 HACEK Organism→ Culture negative Endocarditis
 Sinusitis, pneumonia, brain abscess, Lung abscess
 Infection common in→ Cancers of head and neck; Human Bite infections, DM-1 pts, IVDU's who lick their needles
 VERY FOUL smelling infection
 Tx→ PCN's, Extended sprectrum Cephalosporins, TCN's
Vibrio Cholera
 G- Rod, Comma Shaped, Fac Anaerobe and Fermentor, Oxidase Positive, Single polar flagellum
 O-antigen→ serotypes (need 1billion+ inoculation for infection)
 Sudden onset MASSIVE diarrhea, Protein FREE fluid- dehydration, acidosis, shock→ rice water diarrhea
 Cholera Enteroxin→ AB5- B bind ganglioside, A enters and ADP-ribates Gs→ act ACase and ↑[cAMP]
 TCP pili→ toxin coregulated pili
 Hemagglutins act as adhesins
 zot and ace genes
 Death from dehydration and lyte loss
 Tx→ TCNs adults, Furazolide for pregnant women, TMP-SMX for kids
Vibrio Vulnificus
 Rapid prog. from wound infection (50% mort)→ raw/undercooked shellfish or cont wound during swim or clean shellfish
 Swelling, erythema, pain→ blistering→tissue necrosis, 50% mort\
Vibrio Parahaemolyticus
 Gastroenteritis after raw oyster consumption. May infect wounds but less severe than vulnificus
Proteus Mirabilis
 G- Rod, Lactose Non-ferment, Oxidase Negative, Urease Positive
 Struvite Stones, UTI, nosocomial infections
 Normal GI flora→ enters Lower UT→ urease splits urea into NH4OH and ↑ pH→ ↑ pH leads to precipitations
 Precips formed of NH4/Mg/PO4→ forms struvite calculi→ may block urine flow and dmg kidney/be site of infection
 If bacteria spread to blood→ septic shock
 Dx→ G- rod, Swarming Growth, urease +, ALKALINE URINE!
 Tx→ TMP-SMX; Ampicillin
 Most coomon UTI in nursing home pts w/ catheters
 Produce H2S and Motile

 Salmonella Typhi
 Salmonella Enteritidis
Salmonella Typhi
 O, H antigens and Capsular→ Vi
 Non-lactose ferment and H2S production
 Small intest→ Peyer's Patch → Engulfed by Phagocytes (not killed in MQ) and spread to Liver, Gallbladder and spleen
 Infections→ Typhoid fever (only spread by humans- carry in GB), Carrier state, Sepsis, Diarrhea- Osteomyelitis in Sickle Cell
 #1 cause food-borne infections
 Enterocolitis→ Inv epith and subepith of S/L intestin→ PMN's limit infection (100K needed for infective dose- Susc to Gastric acid)
 Septicemia→ 5-10% infxns (usually underlying chronic Dz)→ Seeds multi-organs (bone, Lung, brain)
 Rose spots on upper abdomen→ erythematous mac-pap rash
 Tx→ Sxs relief
Salmonella Enteriditis
 G- Rod, Motile w/ Flagella, H2S producer, Does NOT ferment lactose
 Treat w/ fluid and electrolytes- Abx reserved for invasive disease and neonates
 Large inoculum required to overcome gastric acid
 No H2S and NON-motile

 Shigella Dysenteriae
Shigella Dysenteriae
 Most effective enteric BUG ( low inoculum required and bacterimia is rare)
 IC Pathogen, G- rod, non-lactose fermenter, Do NOT produce H2S, Non-Motile( actin propulsion)
 No gas production during glucose fermenting

 Sp→ Dysenteriae-A (dev'ing countries); Flexneri-B; Boydii-C; Sonnei-D (mildest an 75% US infections)
 Virulence:
 Targets M-Cells in Peyer's Patch→ Produce Shiga-Toxin (Similar to that made by EHEC)
 Shiga-Toxin→ AB5→ Cleaves 28s rRNA of 60S ribosome
 Inc→ 1-4 days- fever,ab cramps, Diarrhea (watery then bloody w/ mucus)
 Reiter's Syndrome→ Arth/Conj/Urethritis following infection (Y. Enterocolitica, Shigella, Salmonella, K. Pneumoniae, Camylobacter)
 HLA-B27+
 Dx→ Methylene Blue stain on fecal sample shows PMN's
 Trans→ only to humans, Fecal-Oral, Food>Water
 Tx→ Fluid/Lyte replacement, FQN in severe cases, Check Drug resistance *** Abx Tx does not ↑ risk of HUS***
 Motile @ 25C/Non-Motile @37C

 Yersinia Enterolitica
 Bipolar (paperclip) Staining
 Yersinia Pestis
Yersinia Enterocolitica
 G- Rod, Fac Anaerobe, zoonoses, Ox negative and lactose NONferment, grow in cold temps (N. America)
 Pigs, Rodents, Livestock, Rabbits
 Enterocolitis sim to Shigella/Salmonella, Mesenteric Adenitis sim to appendicitis
 Tx→ Chronic Int abscesses←Ampicillin, Chloramphenicol, polymixin
Yersinia Pseudotuberculosis:
 Rodents, Wild animals, Game birds
 Enterocolitis sim to Shigella/Salmonella, Mesenteric Adenitis sim to appendicitis
 Tx→ Severe Intest abscesses→ Ampicillin and TCN
Yersinia Pestis
 G- bipolar staining bacillus (Safetypin)
 Rodents and fleas→ mainly rural in US [NOTIFIABLE Dz]
 Presentations:
 Bubonic (most common): 50% mortality
 Usually lower ext (flea bite)
 Buboes→ enlarged lymph node
 Primary septicemic
 Hypotension, respiratory distress, purpura, DIC
 Pneumonic: 100% fatal
 Cough, fever, hemoptysis
 1º infxn: inhalation
 2º infxn: via bubonic or septicemic
 Dx:
 Safety pin on Gram or Wayson stain
 IFA stain has ↑↑ sensitivity
 PCR in state/CDC labs (also genotyping in these locations)
 Culture
 Serology ( passive hemagglutinations or EIA)
 Management:
 Standard precaution for bubonic
 Pneumonic: droplet precautions for at least 48hrs w/ clinical response to Tx
 Control rats/fleas
 treatment:
 Streptomycin, Tetracycline, chloramphenicol, Gentamicin
 Meningitis: CHLORAMPHENICOL
 DRAIN buboes
Close contact pneumonic prophylaxis w/ doxycycline
 Curved, Small growth on Campy Agar

 Urease Positive
 Helicobacter Pylori
Helicobacter Pylori
 G- rod, curve shape, Microaerophile, 4-6 unipolar flagella, Oxidase, catalase, urease, alk phosphatase POSITIVE
 Chronic active gastritis→ vir factors = motility and urease production (NH3 formation) - also protease and phospholipase
 Killed below pH 4
 Toxins→
 Vacuolating Toxin→ VacA→
 CagA (Cytotoxin assoc gene A)→ ↑ virulence thru ↑dmg of epith cells
 Assoc w/ MALToma→ resolve w/ treatment- PPI plus amoxicillin and metronidazole
 Urease Negative
 Campylobacter Jejuni
Campylobacter Jejuni
 G- rod, Slender comma/S-shaped, Cannot Oxidise OR Ferment Carbs, Motile, Catalase/Oxidase Positive, Urease Negative
 MicroAerophile, CAN Grow at 42C- From poultry
 Invasive enteritis→ Similar to salmonella and shigella→ flattened atrophic villi, necrotic debris in crypts, thickened BM
 Septicemia possible in low CD4 counts
 Some assoc w/ guillain barre syndrome
 Tx→ fluid replacement, Erythromycin (TCN/FQ 2nd), AG's for systemic infection
 Strict Anaerobe
 Bacteroides Fragilis
Bacteroides Fragilis
 G- Neg Rod, Strict Anaerobe, Post-surg wounds, Oxidase and catalase positive
 Peritonitis, GI or Pelvic abscesses (below diaphragm)→ Most common among GI flora
 Makes Vit K for host
 Tx→ drain abscess, repair lesions, Antibiotics (metronidazole/clindamycin)
 Bacteroides (Now prevotella) Melaninogenica→ abscesses above diaphragm
Coccobacilli (pleomorphic)
 X & V factors on chocolate agar
 Haemophilus Influenza
Haemophilus Influenza
 Small G- Rods, Facultative Anaerobe,
 Blood Loving→ req blood factors for growth - X factor (Fe-cont protoporphyrin- for e- TP Chain)and V Factor (vitamin→ NAD)
 Blood enriched media must be gently heated to destroy factor V inhibitors
 Colonizes URT in first few mos of life
 H. Flu biogroup aegyptis→ acute purulent conjunctivitis
 Aphophilis and ParaInflu→ endocarditis and Imm-comp'd infections
 Capsule- MAJOR FACTOR- (Typeable) and Unencapsulated (Non-typeable)
 Non-typables→ infxn of mucosa: OM, sinusitis, bronchitis, pneumonia (Rare dissm)
 Typable→ Polysaccharides (A-F) Capsule→ Majority of invasive diseases (H. Flu type B= 95% all invasive Dz strains)
 Composed of polysorbitol Phosphate (PRP) - ANTIPHAGOCYTIC
 Meningitis, Epiglottitis, etc
 OMP's- P2 and P5 Promote binding to mucosa
 LPS damages ciliated cells
 Adhesins and pili mediate direct adherence to non-ciliated epith cells→ invades cells and subepith space
 IgA proteases cleave IgA
 Binding and Fe/heme uptake allow organisms to persists
 Infection
 Infxn severity releated to rate of clearence; Ab's vs capsule stim Phagocytosis, and complement activity
 ↑ risk if no anti-PRP Ab's, compliment deficient, or post-splenectomy
 Meningitis: #1 cause ped-meningitis prior to vaccine→ 1-3d URT ifxn in young ( HA/Photophobia/Meningismus in older)
 fulminant Dz→ rapid neuro deterioation; Comp's include seizure/cerebral edema/Empyema, SIADH, herniation
 5% mort→ long term if survi: hearing loss, dev delay, visual impairments
 Epiglottitis→ Thumb sign on XR
 Cellulitis and swelling of supraglottic tissue→ acute upper airway obstruction (peak 2-4yo- rare if vacc'd)
 Abrupt onset, high fever, sore throat, dysphagia, sepsis→ AIRWAY MNGT Crucial -ONLY in OR by ENT/Anesth
 Cellulitis: <2
 Cheek, periorbital resion and neck→ Fever w/ unlateral raised, warm area that prog to violaceous hue→ 2º focus in 10-15%
 Arthritis:<2 and some imm-comp'd/elderly
 Fx single large joint d/t bact spread→ fever, ↓ RoMotion → 10-20% with assoc osteomyelitis
 Surgical Drainage and IV Abx
 Conjunctivitis→ H. Flu Aegyptis
 Purulent conjunctivitis in warm months (epidemic)
 Epidemiology:
 Humans natural host, resp-droplet transmit, Bimodal season (Sept-Dec/March-May)
 6-18mos at highest risk→ VACCINE VERY IMPORTANT/EFFECTIVE IN DECREASING INCIDENCE
 Dx→ Susp in non-immiz'd→ Cx: Blood, CSF, Pleural fluid - DO NOT PERFORM THROAT CULTURE IN EPIGLOTTITIS
 Gram stain- G- pleomorphs; Culture on Chocolate or Levinthal Agar- 1-2mm smooth colonies- satellite phenom
 Tx→ B-lactams (3rd gen ceph if serious or PCN and B-lactamase inhibitor)
 Vaccinate- Conjugated PRP vaccine; and Abx Px for close contacts
Haemophilus Ducreyi
 Chancroid→ uncom in US (major elsewhere) G- Rod- hard to Cx
 Tender Papule w/ erythematous Base→ Prog to painful ulceration w/ lymphadenopathy (multi-ulcer possible)
 Dx→Challenging→ Clinical Dx usually- eval for other STI's as well (azithro or Ceftriaxone or cipro or erythto
Aggregatibacter
 Haemophilus Aphrophilus and Actinobacillus→ Mouth Flora (↑ in periodontitis) (HACEK Organisms)
 Actinobacillus often a co-infection of Actinomyces
 Cause→
 Meningitis, Brain Abscess, Soft Tissue infections, Parotitis, Septic Arthritis, Osteomyelitis, UTI, Pneumonia,
 empyema/chest wall infection, ENDOCARDITIS

 Dx→ Suspicion, Cx on Blood and Chocalate Agar, Grows poorly on MacConkey's Agar
 Tx→ 3rd gen cephalosporin! (TMP-SMX, FQ's, TCN's, AG's)
 Growth on charcoal yeast agar with iron and cysteine

 Legionella Pneumophila
Legionella Pneumophila
 G- Rod, Not stain w/ common reagents, Obl aerobe and nut fastidious, rep in MQ's
 16 Serogroups- serogroup 1→ 90% cases
 Grow on amoebae in water→ cooling towers, heaters, spas→ ↑ inc in pts >40yo
 Clinical Syndromes
 Pontiac Fever→ Short-dur, self-lim febrile illness- no Tx needed
 Legionnaires Dz→ Severe-fatal pneumonia- may prog to multi-organ failure (↑ in imm-comped)
 Dx→ Urinary Ag test (LPS antigens of Serogroup 1)/ Cx resp secretions on BCYE)
 Tx→ Macrolides and FQ's→ must penetrate microphages
 Px→ proper building and disinfxn and plumbing design/ routine Cx of hospital potable water→ Nationally Notifiable
 Growth on Bordet-Gengou Medium

 Bordetella Pertussis
Bordetella Pertussis
 G- Rod, Strict aerobe, Fastidious
 Dx→ DFA test, (fast but not specific); PCR
 Colonization→ Non-invasive but has been found in alveolar MQ's→ Aerosol transmission
 Virulence Factors
 Adhesins: Filamentous Hemagluttinin (FHA), Pili and pertactin
 Pertussis Toxin: (S1-S3, 2 S4's, S5)→ ADP-Ribosylates and Inactivates Gi→ ↑ [cAMP] (Invasive ACase)
 Dermonecrotic Toxin- Lethal Toxin.
 Tracheal cytotoxin- Peptidoglycan Fragments
 LPS- Lipid A and Lipid X
 Clinical Stages:
 Incubation (7-10days)
 Catarrhal (1-2wks)- Culture highest- Cold symptoms
 Paroxysmal (2-4wks)- Rep cough, Whoops, Vomiting, Leukocytosis
 Convalescent (3wks+)- ↓ cough, ↑ 2º symptoms (pneumonia, seizures, encephalopathy)
 Tx→ Erythromycin Erad BP and ↓ dur of infectivity but symptoms show late
 DPT Vaccine- 80% effected
 Aerobic
 Brucella
 Bartonella
 Kingella Kingae
Brucella
 Small, non-motile G- coccobacilli (Intracell orgs→ rep in reticuloendothelial system)
 4 spp- Brucella: Abortus (cattle), Suis (Swine), Malitensis (goats/sheep), Canis (dog/coyotes)
 Worldwide (Rare in US→ most from mexico, un-pasteurized dair)
 Tranmission:
 Infects tissues high in erythritol (animal breast, uterus, placenta- high load in milk/birth products)
 Direct contact, inhalation or ingestion of organism
 Sxs: Undulant Fever
 Malaise, fever, chills, sweats, arthralgias→ may become Chronic
 If becomes systemic: GI, respi, bones→ suppurative complications
 Dx:
 Serology
 Serum agglutination test (SAT)
 4x ↑ IgG or single titer ≥1:160
 Culture→ blood/tissue/BONEMARROW (notify lab and inc for 2wks)
 Treatment: ↑ relapse it Tx <6wks
 Doxycycline + Rifampin for AT LEAST 6wks
 TMP-SMX for preg/kids
 Prevent thru livestock control (vacc, elim infected hers, avoid unpast prods)
Bartonella
 Small, curved G- pleomorphic bacillus, Fastidious, and requires long inc (up to 6wks)
 B. Bacilliformis
 Bartonellosis (Oroya Fever/Carrion's Dz)→ 2-6wk incubation
 Acute febrile illness→ severe anemia→ chronic cutaneous form (10% mortality if untreated)
 Spread via sandfly (Lutzomyia): Bite→ bact in blood→ enter RBC's→ fragile RBCs and Acute anemia
 Sxs→ Myalgia, arthralgia, HA→ LAN, Angina, anorexia, MS changes, seizures, abdopain- end w/ humoral immunity (asxs if mild)
 Chronic stage (verruga perunana)→ benign 1-2cm nodules (last mos/yrs)→ angioproliferative and heal on own
 Asxs bacteremia found in 15% survivors→ serve as organisms reservoir
 Tx→ Chloramphenicol in S. America- (Others: Cipro, doxycycline, TMP-SMX)
 B. Quintana
 Trench fever (5 days)→ common in homeless or those w/ poor sanitation (↑ing in AIDS pts)
 Body louse vector (pediculus humanus)→ self limiting ferile recurring illness w/ HA, conjunctivitis, myalgia (low mort)
 Culture Negative Endocarditis→ homeless/Alcoholics→ subacute presentation (F, Emboli, Valvular HDz)
 B. Henselae
 Cat Scratch Disease→ 22K cases/yr→ self-limiting subacute regional lymphadenitis- 1-3 wks (cat bites, scratches or fleas)
 high incidence in cats- no sxs (30% with Ab's, 50% kittens w/ +blood, 30% older cats +Blood)
 Flea vector common
 Warthin Starry stain of lymph nodes→ chains and clusters of organism
 Clinical:
 Papule/Pustule 3-10d after contact→ last 1-3 weeks→ regional LN enlargement 1-7wks later(also F/M/Rash)
 Chronic lymphadenopathy of LN's draining site of contact→ typical presentation- last 2-4 months - spont resolution
 Perinaud's Oculoglandular Syndrome→ Granulomatous Conjunctivitis w/ lymphadenitis
 Granulomatous Hepatitis, Pneumonitis, Neurologic Fx (encephalopathy, neuroretinitis)
 Culture Negative Endocarditis→ Cat exposures→ Subacute presentation→ F, Emboli, Valvular HDz
 Tx→ Debatable on treating→ Azithro for "typical" CSD lymphadenitis
 Bacilliary Angiomatosis
 Ass/w Quintana and Henselae→ ↑ rate in Imm-supp'd
 Raised red/purple lesion that bleeds when traumatized
 1-1000→ sim to hemangiomas→ may be hyperpigmented/hyperkeratotic plaques- overlying osseus defects
 oral mucosa, tongue, oropharynx, nose, penis, anus
 Bone pain (forearms/legs, F/C/M/Night Sweats/anorexia/ Wt Loss, Abdominal Pain, N, V (peliosis hepatis), Jaundice, GI bleeding
 Tx→ Eythro/Azithro OR Doxyclycine→ Treat for 8-12 wks if HIV+ or evidence of endocarditis
 Dx
 Micro→ Giemsa stained blood smears detect B. Bacilliformis in Oroya Fever
 Cultures→ Not recommended w/ CSD lymphadenopathy
 May be useful for henselae/quintana is pts w/ FUO, neuroretinitis, encephalitis, Cx- endocarditis, peliosis, Bacilliary
angiomatosis
 Serology→ Easiest Dx for Henselae and Quintana→ 70-90% sensitivity→ EIA and IF for IgG and IgM
Kingella Kingae
 G- Aerobic coccobacilli→ found in human oropharynx
 HACEK organism→ endocarditis
 Assoc/w "sterile"/aseptic arthritis in children→ pain/fever, children generally recover
 Tx→ PCN's, Extended sprectrum cephalosporins, TCN's
 Requires Cysteine for growth

 Francisella Tularensis
Francisella Tularensis
 G- Coccobacillus
 Reservoir: RABBITS, other animals and their ticks and deerflies
 Human infection:
 Ulceroglandular most common: mac/pap @ entry→ ulcer + lymphadenitis
 Other: Glandular, Oculoglandular, Oropharyngeal, Pneumonic, Typhoidal (HSMegaly), Intestinal
 Dx: Biosafety Level 3!!! Warn lab!
 Ext. caution with micro
 Cx→ cysteine-enriched chocolate blood agar
 **Serology→ 4x ↑ in paired sample OR 1 titer ≥1:160 (may cross react w/ brucella)
 Treatment: Streptomycin >> Gentamicin
 Px: Gloves, Tick removal, Cook wild meats
 Oxidase + and Catalase +

 Pasteurella Multocida
 Oxidase +, Catalase -, Fermentative, and Indole+
 Cardiobacterium Hominis
Pasteurella Multocida
 Cellulitis and Osteomyelitis following cat/dog bites
 Inhabitant of oral cavity of animals→ enters human skin via bite→ local spread to soft tissue and bone→ possible septicemia
 G- coccobacilli, bipolar staining
 Suturing wound may worsen infection→ anaerobic environment
Cardiobacterium Hominis
 Motile, Facultative anaerobe, Small pleomorphic GNR
 Common in resp tract of healthy humans
 HACEK organism→ ENDOCARDITIS
 Dz:
 low virulence, slow onset F and M after bact enter blood through oropharynx
 HDz, Dental Procedure/oral Dz→ Predispose infection
 Dx→1-2wks for detection in broth w/ ↑ CO2 and humidity to grow in agar media
 Tx→ typically Susceptible to PCN's → Ceftriaxone iv OR Ampicillin w/ Gentamycin
The "Other" Bacteria
Acid-Fast
 Thing rods, Non-motile, Obligate Aerobes
 Mycobacterium Tuberculosis
 Grow at low temps and are Phenolase+
 Mycobacterium Leprae
Mycobacterium Tuberculosis
 Slow-growing (13hr gen), Acid-fast Obligate aerobe→ invades MQ's, G+ like cell wall,
 Transmit via PROLONG CONTACT inhale/ingest, resist chemicals/germicides/drying), Waxes in cell wall- Mycolic Acids
 Primary TB→ mild (dmg from formation of granulomas- Ghon Complex- w/ caseous necrosis→ miliary spread if imm-compromised)
 Secondary TB→ reactivation of dormant organisms (dmg from Delayed-typed hypersensitivity rxn to new cells)
 Culture→ Lowenstein-Jensen and Middlebrook 7H10→ lipid-rich media
 Polypeptides in cell wall→ HIGHLY IMMUNOGENIC
 Grow in MQ/monocytes→ prevent phagosome/lysosome fusion (some TB cells may escape via LLO homologue - a Hemolysin )
 May prevent acidification of phagosome (counteract ATPase dep acidification by prod NH4)
 Mycolic Acids are toxic→ stim imm response and cell wall components→ ↑ TNFa and lung damage
 Dx→ Careful History, AF stain on sputum/exudate, CXR, PPD-test, culture for 3-8wks
 PPD warning→ Imm-Comp'd may show false negative and BCG imm'd may show false Positive
 AIDS/TB
 500x normal incidence w/ ↑ extrapulmonary infections (LN's, GU, CNS-photophobia, Miliary)- and ↑ MAI risk (more MDR)
 ↓ CD4 cell number does not allow MQ's to be activated
 Respond to Tx if caugh early
 Tx→ 6-mos of INH, Rifampin, Streptomycin, Ethambutol / Prophylaxis for contacts and at risk / BCG Vaccine
Mycobacterium Leprae
 Acid-Fast, G+ like, obligate aerobe, no growth in vitro
 Armadillo/ footpads of mice; Rare in US (250 case/yr- CA,HI,TX,LA) but 12M case/year worldwide (Asia/Africa)
 Aerosol transmission
 Infx→ histiocytes, epith cells, schwann cells of periph nerves
 Tuburculoid Lerposy→ Th1 response; red-blotchy lesions; dermal granulomas, low infectivity
 Mild and Self-limiting
 Treatment: Dapsone/rifampin for 6mos
 Lepromatous leprosy→ Deficient Th2 response; High inf; Analogous to Miliary TB; large # bacilla in blood (Lepromatous=Lethal)
 VERY SEVERE→ skin lesions diffuse, extensive, depiliated w/ ext. tissue destruction→ analagous to miliary TB (↑ infectivity)
 Treatment: Dr. C→ Dapsone, rifampin, clofazamine (2+yrs of Tx); Bx must be neg for AF rods
 Dx→ Skin reactivity to lepromin or Acid Fast bacilli in skin lesions
Mycobacterium Avium Intracellular Compex (MAI)

 Slightly faster growing than MTB→ acid fast bacilli in MQ's
 2nd only to TB in Sig and Frequency→ most common Mycobacterial infection in AIDS Patients in US→ syst infxns in HIV
 Dx via Blood Culture
Mycobacterium Kansasii
 Photochromogenic mycobacterium→ yellow pigment when Cx's in light for 2wks
 ↑ incidence since TB have ↓'d→ Most common in IL, OK, TX
 Cause Cavitary Pulmonary Disease, cervical lymphadenitis, skin infections← HIV w/ CD4 <200c/mL
 PPD positive- remembles TB→ Tx with prolong chemotherapy INH, RIF, ethambutol
Spirochetes
 Microaerophilic, and sensitive to high temperatures
 Treponema Pallidum
Treponema Pallidum
 Spirochete→ helical G- (use dark field)→ cannot grow in cell free Cx
 #3 STI in US
 Outer membrane with endotoxing-like lipids
 Epidemiology→ Direct lesion contact to spread (~21day inc)→ ↑ HIV trans risk (63% w/ MSM/ Af. Am→ ↑7.9xwhites)
 Sxs→
 tissue destruction from immune response
 Early→ Primary (chancre- painless) 10-90days post exp→ heal spont w/n 2 mos
 Secondary (1-2mos then rash(palms and soles)/mucocut lesions (condyloma lata and lymphadenopathy)
 endarteritis and periarteritis, flu-like
 Early Latent→ asxs
 Late Latent→ Great imitator→ 1+yr infection→ neurosyphilis (cns/ocular)
 tertiary stage→ (15-30yrs) Gummas (granuloma) in skin/viscera/bone/aortitis; Charcot Joint from ↓ proprioception
 Neurosyphilis→ 1/3rd→ paralytic dementa, Tabes Dorsalis, AML Sclerosis, Seizures, Optic Atrophy, Gummas of Cord
 CardioVascular→ 10-40 years→ great vessel arteritis, aortic regurg or stenosis of coronary ostia
 Congenital→ severe Dz (in utero infxn)
 first asxs→ rhinitis and desquam rash→ teeth/bone malform (hutchinson teeth)/ saddle nose, blind/deaf in untreated
surviviing initial phase
 Screen MOMS!!!!
 Dx
 No Cx→ Dark field to ID (springy motility)-
 BEST IS→→ VDRL/RPR and confirm w/ treponemal tests FTA-ABS/TP-PA/EIA
 SLE/RA (auto-imm)/preg→ false +
 Jarish-Herxheimer Reaction (after PCN Tx)→ sxs from large ↑ TP lipopolysaccharides→ fever/HA/Myaldia/HypoT w/24hrs (spt care)
 Monitoring after Tx→ Serum VDRL/RPR after 3 and 6 mos (then every 6mos for 2yrs)→ 2nd course Tx is no 4fold↓ after 6mos
Treponema Pertenue
 Yaws→ Gran Dz w/ skin lesions during early Dz; Late→ dest lesions of skin,lymph,bone (SABER SHIN)
Treponema Pallidum Endmicum

 Bejel→ Endemic Syphilis; Spread by direct contact of early lesions
 Gummas of Skin, bone, nasopharynx are late lesions
Treponema Carateum
 Pinta→ Primary FX on skin→ Small prurituc Papules→ enlarge and persist mos-yrs→ scarring/disfigurement
 Giemsa & Silver staining, Microaerophilic

 Borellia Burgdorferi
 Borrelia Recurrentis
Borellia
 motile (flag) Weak staining G- spirochete (difficult to Cx)
Borrelia Burgdorferi (Lyme Dz)

 #1 vector-borne in US (NE/Mid-Atl; MN/WI; NW)- ↓ with tick control
 Vector: Ticks (ixodes scapularis & pacificus)→ bite ≥36hrs→ salivary transmission
 Reservoir: White-tailed deer/ white footed mouse
 Sxs: Incub up to 1mo→ 3 stage Dz
 Early Local: Bulls-Eye rash (erythema migrans-EM) **
 Early Dissem: multiple EM's, facial nerve palsy, meningitis
 Late Dz: arthritis, carditis
 Dx: Clinically → EIA/IFA→ confirm w/ western blot
 Tx: Doxycycline if over 8yo

 Amoxicillin/Cefuroxime for kids
 Ceftriaxone for CNS, Carditis, arthritis
Borrelia- relapsing fever

 40% mortality
 Epidemic (louse-borne)→ B. Recurrentis
 Endemic (Soft-shell-tick-borne)→ B. spp. (rodent reservoir: tick fd @ nite, defecate on wound)
 Sxs: 1 wk inc- Biphasic
 Phase 1: F/Ch/HA/HSmegaly then 1 wk no sxs
 Phase 2: Sxs recurr
 Dx→ febrile state giemsa on periph blood (serology useless d/t phase variation)
 Treatment: Doxycycline [PCN/Erithromycin if under 8 or pregnant]
STARI- Southern Tick Ass. Rash Illness

 Lyme Dz sxs in non-lyme Dz area (EVERYWHERE BUT NE US, WI/MI and little teeny tiny locations in CA and Oregon)
 Assoc/w lonestar tick: B. Lonestari (PCR on ticks→ spirochetes)
 Dx on sxs and epidemiology
 Treatment→ doxycycline and amoxicillin
 Aerobic, "Ice-Tong" appearence (Chinese letters)

 Leptospira Interrogans
Leptospira Interogans
 ?-mark shaped spirochete- Poor stain- use dark field (13named/4unnamed)
 Free living or assoc w/ animal (surv in water/soil/mud in tropical areas)
 Infxn: abrasion/cut in skin or thru conjunctiva and mucous membranes
 Direct contact w/urine or reprod fluids
 Prolong immersion→ ↑ risk (triathlon outbreaks)
 Rarely thru bites or person-person
 Sxs: Self-limited in 90% (flu-like)
 Weil syndrome: life-threatening w/ jaundice and renal dysfunction
 Biphasic:
 1- septicemia
 2- immune mediated (F, aseptic meningitis, uveitis, purpuric rash)
 Dx→ SEROLOGY (MAT-microscopic agglutination test)
 Ab's w/n 5-7days of sxs
 Cx or darkfield microscopy INSENSITIVE; NO PCR
 Treatment: PCN is DoChoice w/ severe Dz / Doxycycline for mild
 Prevent- doxycycline 200mg for high risk exposure/ Vacc animals/ rodent control
Non-Gram Staining
 Mycoplasma Pneumoniae
 Chlamydia Psittaci
 Chlamydia Trachomatis
 Chlamydia Pneumoniae
 Rickettsia Rickettsii
 Rickettsia Prowazekii
 Coxiella Brunetti
Mycoplasma Pneumoniae
 Smallest free living bacteria→ No cell wall and sterols in cell membrane; Pleomorphic, STRICT AEROBE
 Growth req supplemental source of cholesterol
 Pathos→ Adhere to resp epith via P1 (terminal adhesion protein) binding glycoprot receptor at base of cilia→ ciliostasis and destruction of
epithelial cells
 Loss of cilia→ ↓ mucus clearance→ continue to lower resp tract→ Chronic cough transmits via respiratory drops
 M. Pneumoniae→ acts as SUPER ANTIGEN→TNF-a, IL-1, IL-6
 Epidemiology→ Contagious as long as coughing
 Strict human pathogen→ worldwide and year long w/ ↑ in summer and fall
 Epidemics 4-8 years and lasts 12-30 months (most common in 5-15yo)
 Clinical Syndromes
 Mild URTI #1
 Otitis Media→ bullous hemorrhagic myringitis
 Tracheo Bronchitis→ low grade fever, M, HA, dry non-prod cough 2-3 wks after exp and persist wks
 Pneumonia→ Walking pneumonia→ Patchy bronchopneumonia on CXR
 Complications: Pericarditis, Hemolytic anemia, Neurologic Anomolies, Arthritis, Erythema Multiforme, SJS
 Dx→ Serology→ IgM/IgG- 4x titer↑
 PCR- sensitive but variable spec
 Cx= Rel insensitive, Special media for serum, yeast extract, glucose, pH indicator and penicillin→ Gluc metab and pH change
 Tx→ Macrolides, TCN's, FQ's (avoid TCN and FQ in children)→ reserve for Dz with serious complications
Mycoplasma/Ureaplasma
 Mycoplasmataceae family→ SMallest free-living bact (no Cellwall→ sterols in cell membrane) Not seen in gram stain/slow growing
 Ureaplasma→ reservoir is GuTract of sex active adults→
 non-gonococcal urethritis/prostatitis/epydidimitis/Salpingitis/Endometritis/chorioamnionitis
 Culture→ treat only if + and showing sxs→ PCR (rarely available) and serology insenstive and non-spec
 Tx→ doxycycline and azithromycin
 Mycoplasma Homonis→ Normal flora→ pyelonephritis/PID/Chorioamnionitis/post-partum/abortal fever
 Dx→ Cx(difficult)/ PCR
 TX→ doxycycline
Chlamydia Trachomatis
 OIP, G-non-staining- Rod with NO peptidoglycan layer= EB's are inactive but infectious; RBs active but non-infectious
 Limited cell range for infection→ nonciliated columnar, Cuboidal, and transitional epith
 #1 STI in US→ ↑ adolex/yadults==>
 Serovars→ Based om MOMP
 A,B,Ba,C= Trachoma
 Lead to scarring/blindness→ leading cause blindness worldwide- Afr,Asia,S. Ame
 Children→ primary infection and resevoir→ spread via eye droplets, flies, hands, clothes
 Herberts pits→ shallow pit in cornea from follicular rupture(pathognomonic)
 Dx→ 5+ white/yellow spots on upper tarsal conj
 2 Stages→ Active Trachoma and Cicatricial Disease
 Active Trachoma→ Mild-self-lim follic conjunctivitis→ Sup tarsal conjunctiva
 Cicatricial Disease→ Dep on sev and duration of active phase → corneal opacity and blurred pupil margin
 repeat infections→ inflammation and eyelid scar→ entropian and trichiasis (Trichiasis leads to blindness)
 Trichiasis→ eyelid conjunctiva Scar tissue contracts→ cause eyelash to rub cornea
 Pannus→ Growth of vascular tissue over cornea
 D-K= Urogenital Tract dz→ May progress to PID

 Lead to scarring, sterility and sexual dysfunction→ cervical infection and PID
 F→ most asxs (resevoir/ Cervicitis/Endometritis/Bartholitis/Salpingitis/Erethritis possible)
 M→ Most w/ sxs (Urethritis/Epidydimitis)
 Cervicitis→ erythematous and friable w/ mucopurulent discharge from os
 Fitzhugh-Curtis Syndrome→ Perihepatitis with inflam of liver capsule
 L1-3= LGV::Lymphogranuloma Venereum→ more invasive d/t rep in MQ phagosomes
 Rare in US→ ↑ in tropics (resolve or become chronic→ fistula/strictures/genital elephantiasis) w/ common HIV coinfection
 exp→ 1-4wk inc→ non-painful Papule/ulcer primary ± sys sxs→ Second inflamm and swell LN's (buboes may rupture)
 Procto colitis in men and women thru anal intercourse
 Untreated→ resolve or chronic (Form fistulas, strictures, genital elephantiasis)
 Perinaud Oculoglandular Syndrome→ LGV types→ Conj inflam w/ pre-auric,Submand, and cerv lymphadenopathy
 Other infections:
 Newborn inclusion conjunctivitis→ Acquired thru b-canal (25% w/ act mat infxn)
 5-12 days then swollen eyelids, hyperemia, purulent discharge
 Adult inclusion conjunctivitis→ 18-30yo's
 Precede by Genital infection→ auto-inoc via oral-gen contact
 Mucopurlent discharge, Keratitis, Corneal infiltrates, scarring
 Reiter's Syndrome→ Urethritis, Arthriits, conjunctivitis and mucocut lesions
 Infant Pneumonia→ 2-3wks after birth→ rhinitis and staccato cough and tachypnea→ afebrile w/ CXR hav bilateral interstit infil's
 Dx→ IF or genetic probe
 Culture req Epith cells!!→ only test accepted in criminal case (less sens than NAA but more spec)
 Serology NOT recommended→ NAA available- PCR, TMA, SDA (urethral/endocervical swabs)
 Cytology for cell inclusions
 Antigen detection→ DFA, ELISA
 Annual testing for sexually active women <25
 Tx→ 7day doxycycline (21 for LGV) or 1 dose Azithromycin (Eval/Tx partners!!!)- some FQ's→ Reiter's may follow treatment
Chlamydia Psittaci
 Seen in parrots→ blood, feces, tissues, feathers→ PET SHOP EMPLOYEE w/ pneumonia
 Colonize URT then spread to reticuloendothelial cells of Liver and spleen
 Inc is 5-14 days→ onset vary (HA,F,M,Pharyngitis and cough)- (mild to fatal systemic illness w/ resp compromise
 Dx→ Conf case req clinical illness AND lab confirmation via IgM MIF** or 4x↑ titer
 Tx→ TCN's (MQ fq's show some effectiveness)
 Px→ Tx birds w/ TCN for 45days, qarantine them before sale- NATIONALLY NOTIFIABLE
Chlamydia Pneumoniae
 Normal WBC count and CXR with patchy Infilt→ ↑ inc 65-79yo
 Transmit via resp secretions→ asxs to mildly sxs→ imm is short-lived with reinfections common
 Possible link to CAD
 Dx→ Serology Ig by MIF
 Tx→ Treat on Clinical Suspicion! MQ's, TCN's, levofloxacin, moxifloxacin
Rickettsia
 weakly G- bacilli with MINIMAL peptidoglycan layer
 OBLIGATE Intracell parasite→ rep in cytoplasm of cells → Require CoA and NAD+ to grow
 Stain w/ Giemsa/Gimenez
 Treatment (unless otherwise stated)→ Doxycycline (TCN's) with Alternatives as Chloramphenicol and FQN's (Tx on suspicion)
 Dx: on clinical suspicion and epidemiology→ IFA serology #1 confirm/ PCR most specific
Rickettsia Rickettsii
 Rocky Mountain Spotted Fever (RMSF)→ #1 human rickettsia in US, 90% april-Sept→ 20% mort if untreated
 Omp A → Adhere to endothelial cells
 Replication in cytoplasm & nucleus→ vasculitis
 Vector & reservoir: Ticks (Ixodes)→ Wood Tick (Dermacentor andersoni- RM's); Dog Tick (Dermacentor variabilis- SE US)
 Transovarian tick Transmission/ 6-10hrs post bite for human transmission (bact. act by warm blood meal→ enter hum from saliva)
 SXS:
 2-14inc→F,HA,myalgia→3-5dys→centripetal RASH in some (eryth mac/pap→petechiae) can affect palms and soles
 Other: Abpain, V, hepatitis; Resp failure; encephalitis; renal failure; Hypotension, myocarditis
 Labs:
 Thrombocytopenia, coagulopathy, anemia, hyponatremia, transaminitis
 NORMAL WBC count
 Dx→ Dx is clinical and epidemiologic
 Serology #1 (may be neg in early case)→ 4x ↑ of IgG in IFA week 1 then week 2-4
 PCR and IHC stain during 1st week
 Culture possible
Rickettsia Akari- (Rickettsial Pox)
 Vector: infected mites (Humans accidental host)
 Reservoir: Rodents
 Sxs: Biphasic Dz (milder than RMSF)
 Phase 1: 1 wk post-bite=> papule→ulcer→eschar (anthrax only has eschar)
 7-24dys→systemic spread
 Phase 2: High fever, severe HA, photophobia Papulo-vesicular rash w/ poxlike progession (vesicle→crustover)
 Complete healing→ 2-3wks
Rickettsia Prowazakii- Epidemic (louse-borne) typhus
 Human reservoir (rare in US← flying squirrel carrier- flea is vector [squirrel louse doesn't bite human])
 Wars/Famine/Distasters
 Louse feces infect bite/abrasion (long infectious life)
 Sxs:
 Acute:
 Potentially severe vasculitis (1-2wks after inoculation)
 Fever, centrifugal rash (mac/pap), CNS fx
 Recrudescent: Brill-Zinsser Dz
 10-50years after primary infxn
 milder form→ rash, flu-like sxs (elderly→WWII)
 Dx→ Serology MIF test
Rickettsia Typhi- endemic (murine) typhus
 warm/humid areas: Rodent reservoir
 Vector: Rat flea (xenopsylla cheopsis) and Cat flea in US (C.Felis)→ feces inoculates bite wound
 Sxs: mild, nonspec→ F,HA,Chills,myalgia, rash with variable presentation
 Dx- Serology IFA
Orientia Tsutsugamushi - Scrub Typhus (former rickettsia)
 Vector and reservoir: Mites (larval mites/ chiggers)→ transovarian transmission, live on vegetation
 Asia/Pacific rim
 Sxs: Severe HA, fever, myalgia
 Centrifugal mac/pap rash, CNS complications, Heart failure
 Dx- IFA serology
 Treatment → Doxycycline (TCN's) with Alternatives as Chloramphenicol and FQN's (Tx on suspicion)
Coxiella Brunetti
 Q Fever (zoonoses- prevent with farm safety practices)
 Worldwide: cattle/sheep/goats/dogs
 Transmit via inhal of aerosols (birth fluids/dust) or direct tissue exposure (HIGHLY INFXOUS)
 ***Unpasteurized products***
 Sxs: 60% subclinical-  dx:
 Acute infxn:  Serology
 HA, hi fever, chills, myalgia, 50% w/  Acute: Phase II Ag (IgM/IgG)
hepatosplenomegaly  Chronic: Phase I>>>Phase II Ab's
 Atypical Pneumonia  Culture rare done (Safety hazard)
 Chronic: RARE  Treatment: Doxycycline→ ADD hydroxychlorquine in
 typically in pregnancy or imm-supp'd chronic Dz
 incubat→ mos to yrs→ subacute endocarditis
Erhlichia & Anaplasma
 Obligate intracell bacteria, NO peptidoglycan OR LPS
 Grow in hematopoietic cells (rep in phagosomes)
 Morula→ microcolony w/n a vaculuole (erhlichia)
 Tx- Doxycycline REGARDLESS of age → highly responsive
 prevent with insect control/tick removal
Erhlichia Chaffeensis (HME→ Human Monocytic Ehrlichiosis)

 Reservoir: deer, dogs
 Vector: ticks (amblyomma americanum)
 SE, SC, and MW states (MO,OK,AR)
 Sxs: 3% mortality
 1-3wk inc: flu-like illness w/ late rash (1wk after onset)
 Dx: IFA serology, PCR (Periph blood Giemsa→morula in monocytes)
Anaplasma Phagocyphilum (HGA→ Human Granulocytic Anaplasmosis)

 Reservoir: deer, sheep, rodents
 Vector: hard shell ticks (ixodes scapularis and pacificus)
 NE/NC states & N. Cali
 Sxs: 1% mortality
 1-3wk inc: flu-like illness w/ late rash (1wk after onset)
 Dx: IFA serology, PCR (Periph blood Giemsa→morula in granulocytes)
Bacterial Vaginosis
 Sexually active fem→ change in vag flora→ thing white/grey adherent homogenous vag discharge w/ fishy odor→ pruritis/dysuria/asxs
 Can occur w/ trich/candida infxn and can →PID
 Cause not clear→ usually ↑ in gardnerella vaginalis/mycoplasma/ureaplasma and anaerobes (mobiluncus/prevotella)
 ↓↓↓ in lactbacillus
 Gardnerella presence not adequate for Dx
 Dx→ 3 or more signs→
 Thin white/grey non-inflam discharge
 Vag pH>4.5 w/ fishy odor (before or after KOH "whiff" test
 Clue Cells!!!→ Squam vag epith covered w/ bact
 Tx→ relieve sxs→ metronidazole (oral/gel) or clindamycin cream
Viruses
Anti-Viral Drugs:
5 Major Antiviral Drug Categories/Targets:
1. Herpes Family Viruses
2. Cytomegalovirus
3. Influenza (types A and B)
4. RSV (bronchiolitis in children)
5. HIV
Acyclovir
 Phosphorylated to the inactive monophostphate form by a virus specific thymidine kinase and then to the active form by cellular enzymes
 Kinetics:
 Renal elim (60-90%) ADJUST FOR RENAL FXN
 Bioavailable→ 10-30% w/ good CSF/placenta/umbilical penetration
 ADRs:
 IV form→ phlebitis or inflam @ site of infusion
 Reversible renal toxicity d/t crystalline nephropathy in 5-10% receiving IV tx
 CNS→ SEIZURES**, tremor, hallucinations
 hepatotoxic (hyperbili, jaundice, Hepatitis)
 Uses:
 Herpes Lesions/Rash (if started in 72hrs) (Genital herpes simplex)
 IV formulation for encephalitis
 NOT EFFECTIVE VS CYTOMEGALOVIRUS
Valacyclovir
 Acyclovir prodrug → L-Valyl ester (allows less frequent dosing)
 Coverted via 1st pass metab in liver→ 70% bioavailability
 High doses (confusion, hallucinations, nephrotoxicity and RARE BUT SEVERE→ THROMBOCYTOPENIC syndromes
 Uses→ Herpes Zoster; Herpes Simplex;
Ganciclovir
 Acyclic nucleoside analogs of gaunine (similar to acyclovir)
 MoA:metab'd by thymidine kinase and other enzymes to triphosphate analog which inhibits DNA polymerase when inc'd into viral DNA
 Kinetics:
 10x more effective vs CMV and EBV than acyclovir and equally effective vs HSV and VZV
 6-9% bioavailable
 ADRs:
 Bone Marrow suppression (Neutropenia>>>thrombocytopenia>anemia)→ reversible
 CNS→ HA/Behavior changes
 GI (Nausea and Vomiting)
 Uses:
 CMV retinitis (intravitreol), CMV prophylaxis
Valganciclovir
 Prodrug of gancyclovir→ L-Valyl ester
 Kinetics:
 Bioavailable ~60% and ↑'s w/ high fat meal→ Renal excretion and req's adjustment
 Uses: CMV Retinitis and Px
Penciclovir
 Acyclic guanine nucleoside analog→ only in US as a 1% topical cream
 ADRs→ HA and irritation @ application site
 Uses→ HSV cold sores
Famciclovir
 Penciclovir prodrug→ sim to acyclovir
 Bioavailable (65-77%)→ RENAL EXCRETIONS
 ADRs: CNS (HA) and GI (N/V/D)
 Uses: Herpes Zoster Tx; Herpes Simplex; Recurrent mucocutaneous herpes simplex
Cidofovir
 Diphosphate interacts w/ DNA polymerase (alt substrate or a competitive inhibitor)→ activation does not require thymidine kinase
 ADRs: Highly NEPHROTOXIC; Neutropenia, ocular hypotony, metabolic acidosis
 Uses: Admin w/ probenecid or normal saline to ↓ nephrotoxicity→ 1wkly dose→ CMV retinitis AIDS pts that failed ganciclovir tx
Foscarnet
 Competes for pyrophosphate sire in viral BUT NOT human DNA polymerase and reverse transcriptase
 An inorganic phosphate that does not require phosphorylation by thymidine kinase
 ADRs:
 Nephrotoxic; Electrolytes******, CNS (seizures); N/D/V; Cardiology (EKG changes; 1st degree block, hyper/hypotension)
 Uses:
 Second line agent d/t HIGH RATE OF ADRs
 CMV Retinitis; Acyclovir resistant mucocutaneous Herpes Simplex in Imm-Supp'd
Interferons
 Potent antiviral, immunomodulating and antiproliferative cytokines
 Kinetics:
 Oral Admin→ no detectable levels
 IM/SQ Admin→ allows absorption
 ADRs:
 Acute influenza type reactions (HA/Chilles/Myalgias/Arthralgia/N/V/D)
 Myelosuppression( Thrombocytopenia/Granulocytopenia)
 Neurotoxic: Depression, confusion, somnolence, rare seizures
 Alopecia and Personality Changes (common in children)
 Uses:
 Conyloma Acuminatum (intralesion injection); Chronic Hep B and C; Kaposi's Sarcoma; Multi-Sclerosis
Lamivudine
 Originally used as an anti-retroviral agent
 MoA: Metab'd IC to ddATP→ inhibits reverse transcriptase and incorporates into viral DNA→ chain termination
 Kinetics: Biolavailability (80-90%)→ renal elim
 ADR's→ LACTIC ACIDOSIS and SEVERE HEPATOMEGALY (fatty liver steatosis); D; CNS(HA/F/Insomnia/Peripheral Neuropathy; Arthalgia
 Uses: HBV******* and HIV
Ribavirin
 MoA: Unknown
 Kinetics: 50% bioavailable; Food ↑ abs; Halflife is 200-300 hours***; Renal Elim
 ADRs: Dose related anemia; Comb/w IFN→ ↑ risk of fatigue/rash/pruritis/depression
 Anemia leads to HIGH rate of d/c
 Uses: RSV bronchiolitis and pneumonitis; Hepatits C virus (std Tx comb/w IFN-2a or 2b)→ G1=48wks; G2/3=24wks
Imiquimod
 Topical Tx for conyloma Acuminata
 MoA: Induces local IFN-a.B.gamma and TNF-Alpha→ ↓'s viral load and wart size
 3/wk for up to 16wks→ complete clearance in 50% pts→ relapses are not uncommon
Amantadine/Rimantadine
 Px and Tx of Influenza A (Imp to start w/n 24hrs)
 MoA: Prevents virus from entering susceptible cells
 Renal Elim (adjust dose in failure)
 ADRs: CNS (anxiety/Nervousness/Confusion/Insomnia) Amantidine>Rimantidine
 Amantadine→ some effects on Tx of parkinsonism
Olsteltamivir/Zanamivir
 Px and Tx of influenze types A and B**
 MoA: Specific inhibitor of Influenza virus Neuraminidase
 Ostelt: N/V/Abdo discomfort from local irritation→ resolve in 1-2 days and mild/mod in nature→ ↓ by taking w/ food
 Zanam: oral inhalation of dry power well tol'd→ discouraged in COPD and Asthma
Anti-RetroVirals:
Nucleoside Reverse Transcriptase Inhibitors (NRTI's)
 MoA: Structurally similar to nucleic acids of RNA/DNA→ PO4'd by IC cellular kinases→ blocks reverse transcriptase
 Inhibition via Competing w/ natural substrates and incorp'ing into viral DNA to terminate chain
 ADR's All→ All may cause lactic acidosis with hepatic steatosis; usually no Drug-Drug interactions
 ****Check for HLA-B*5071 before admin of Abacavir****
Abacavir Lamivudine
 High Bioav→ 2hr t.5  90% bioavailable
 Hepatic Metab (dehydrogenation and glucuronidation)  ADRs: D/N/HA/Insomnia (very low toxicity)
 ADR: Fatal hypersensitivity syndrome (F/M/Abdo Pain/
Rash/ SoB) AND Anorexia Stavudine
 90% bioav
Didanosine  ADRs: Periph neuropathy*; ↑ LFTs; Lipatrophy**
 Food (Acidity) ↓Fx
 Metab'd via purine metab pathway Zalcitab
 ADRs: Peripheral Neuropathy and pancreatitis  ADRs→ SEVERE peripheral Neuropathy; Oral Ulcerations and
stomatitis
Zidovudine
 High fat ↓ Fx Tenofovir
 Metab via glucuronidation  ADR→ Flatulence
 ADR: Bone Marrow Suppression (anemia); GI intolerance;
Insomnia; NAIL PIGMENTATION Emtricitabine
 Hyperpigmentation of the skin, Well tol'd like lamivudine
Nonnucleoside and Nucleotide Reverse Transcriptase Inhibitors (NNRTI's)

 MoA: Bind directly to reverse transcriptase (Do not need PO4'd to become active and are not incorporated into viral DNA
 Special Chx: Extensive cross-sensitivty in class; Rashes frequently in the 1st four weeks
 Resistant emerges quickly in monotherapy
 Metabolic Autoinduction (Nevirapine and Efavirenz)
Nevirapine
 90-93%
 Metab: 3A4>2B6 and induces*** 3A4
 ADRs: RASH; ↑ LFTs; DO NOT START IN WOMEN IF CD4+ count is >400 d/t ↑ liver tox
Efavirenz
 Metab via 2B6>3A4→ Induces 3A4
 ADRs: RASH; ↑LFT's; CNS sxs→ insomnia; Nightmares; Mania; impaired cognition→ RARE SJSyndrome
Delvaridine
 Metab via 3A4; INHIBITS 3A4→ do not take with antacids
 ADRs: Rash and Headache
Tenofovir
 Also and NRTI→ Renal filt and active secretion
 ADRs: GI tox; HA; May cause lactic acidosis with hepatic steatosis
Protease Inhibitors (PIs)

 MoA: Inhibit HIV-1 Protease (complex enzyme resp for cleaving large viral polypeptide chains into functional proteins)
 Special Chx: All Metab via Hepative oxidative metabolism (active in both acute and chronically infected cells)
 PIs→ Hyperlipidemia; Fat Maldistribution; Insulin resistance and DM; osteonecrosis→ ENDROCRINE DISTURBANCES
 Ritonavir→ commonly prescribed to BOOST other PI levels at lower doses
Saquinavir Amprenavir
 Metab 3A4 (weak inducer)→ DO NOT USE W/ INDINIVIR  3A4
 Mild GI intolerance; fat ↑570%  N/v/D; Rash; Fatique; Parasthesias; GI intolerance;
Indinavir Fosamprenavir
 Metab 3A4  PRODRUG for amprenavir
 Alopecia; dry skin/lips; Kidney stones; Hyperbilirubinemia; GI  Add oral parasthesias; ↑ LFTs
intolerance;
Tipranivir
Ritonavir  3A4 metab→ HEPATOTOXIC; Rash (Sulfa allergy); good for PI
 Metab 3A4>2B6 resistant virus
 Parasthesia; taste disturbances**; Anorexia; CROSS
RESISTANCE WITH INDINIVIR; GI intol Darunavir
 3A4 metab→ Rash (Sulfa Allergy); good for PI resistant virus;
Nelfinavir hepatoxic
 Metab 2C19>3A4
 AVOID IN PREGNANCY; diarrhea; Atazanavir
 3A4 Metab→ Hyperbilirubinemia leading to jaundice;
PROLONG QT interval heart block
Fusion Inhibitors (entry inh)

Enfuvertide
 MoA: interfere w/ entry of HIV-1 into cells by inh fusion of viral and cellular membranes
 Binds first heptad rpt (HR1) in the gp41 subunit
 Special Chx: Only available as SQ injection→ HALLMARK ADR→ injection site irritation/nodules
 Costly, incovenient delivery system; Cutaneous tox reserve (for pts that fail with other antiretrovirals)
CCR5 Antagonists (entry inh)

Maraviroc (selzentry)
 MoA: binds CCR5 receptor of CD4 T-Cells
 Indications and special Chx: Tx experienced HIV infected pts infected solely with R5 strains
 ADRs: Abdominal pain; cough; dizziness; musculoskeletal sxs; purexia; rash; URT infection; hepatotox; orthostatic hypotension
Integrase Inhibitors
Raltegravir (Isentress)
 Inh strand transfer of viral DNA to host cell DNA
 Used in treatment experienced HIV+ pts
 ADRs: N/D;HA;pyrexia; ↑ CPK
Antiretroviral Combo's to AVOID

 Atazanavir and Indinavir→ Additive hyperbilirubinemia
 Didanosine+Stavudine→ ↑ tox incidence (periph neuropathy; pancreatitis; hyperprolactemia)
 Efavirenz during 1st trimester→ Teratogenic in nonhuman primates
 Emtricitabine + Lamivudine→Similar resistance profile with no potential benefit
 Nelfinavir in pregnant women→ EMS in final product→ animal carcinogen, mutagen, teratogen
 Stavudine + Zidovudine→ Pharmacologic antagonism
HAART
Highly Active Anti-Retroviral Therapy
Virus Overview
A Quick Rundown
The big picture:
For DNA Viruses:
1) ALL contain dsDNA→ EXCEPT: Parvovirus
2) ALL are naked (NO ENVELOPE)!!!! → EXCEPT: Herpesviruses, Poxviruses, Hepadnaviruses
3) ALL have an ICOSOHEDRAL capsid and replicate in the NUCLEUS!!!!! Except- Poxviruses- complex and cytoplasm (remember the brick)
For RNA Viruses:

1) ALL Contain ssRNA→ Except Reoviruses
2) ALL - RNA viruses must code for their own RNA-dependant RNA polymerase (aka virion polymerase)!
3) ALL have are enveloped→ Except- Calciviruses(+ssRNA), picornoviruses (+ssRNA), and reoviruses(dsRNA)- think GI bugs
4) ALL have HELICAL capsids→ Except-
a) Calciviruses, Flaviviridae, Picornoviruses , and togaviruses (+ssRNA)→ Complex
b) reoviruses (dsRNA)
5) ALL replicate in the CYTOPLASM→ Except- Orthomyxoviruses and Retroviruses which also have a nuclear phase
6) ALL +ssRNA viruses have ss, linear, nonsegmented genomes→ Remember retroviruses are diploid +ssRNA
7) ALL -ssRNA viruses have ss, linear genomes→ except Bunyaviridae and HDV (both circular)
8) Arenaviruses are oddballs→ circular ambisense ssRNA
A virus with an envelope→ ↑ susceptibility to digestive processes
Inclusion Bodies:
Eosinophilic intracytoplasmic Inclusions: Basophilic intranuclear inclusions:
 Negri Bodies (Rabies Virus)  Cowdry Type B (Adenovirus)
 Guarnieri Bodies (Smallpox Virus)  Owl's Eye (Cytomegalovirus)
 Henderson-Peterson Bodies (Molluscum Contagiosum Virus)
Intranuclear and Cytoplasmic inclusions:
Acidophilic intranuclear inclusions:  Warthing Finkeldey Bodies (Measles)
 Cowdry Type A ( Herpes Simplex Virus, Varicella Zoster Virus
 Torres Bodies (Yellow Fever)
 Cowdry Type B (Polio Virus)
DNA Virus Overview:

For DNA Viruses:
1) ALL contain dsDNA→ EXCEPT: Parvovirus
2) ALL are naked (NO ENVELOPE)!!!! → EXCEPT: Herpesviruses, Poxviruses, Hepadnaviruses
3) ALL have an ICOSOHEDRAL capsid and replicate in the NUCLEUS!!!!! Except- Poxviruses
Viral Families (With prime example):

 Adenoviridae- Adenoviruses
 Hepadnaviridae- HBV
 Herpesviridae- HSV, VZV, CMV, EBV
 Papillomaviridae- HPV
 Parvoviridae- B19 Virus
 Polyomaviridae- JC Virus
 Poxviridae- Smallpox virus, Vaccinia Virus, Molluscum Contagiosum Virus
Oncogenic DNA Viruses of Humans: Transform NON-permissive cells

 Human Adenovirus Animal Tumor Viruses:
 Epstein-Barr Virus  Marek's Disease Virus (Chicken Herpesvirus)
 Hepatitis B Virus  Polyomavirus ( Mouse Papovavirus)
 HSV-2  SV-40 Virus (Monkey Papovavirus)
 Polyomavirus
 SV-40 Virus
 Molluscum Contagiosum Virus, JC and BK Viruses
RNA Virus Overview:

RNA "Sense" refers to the ability of the virus's RNA to act as mRNA in the cell cytoplasma. (+RNA=mRNA)
Conversely, -RNA required virion polymerase to make +RNA (RNA-Dependant RNA polymerase).
For RNA Viruses:

1) ALL Contain ssRNA→ Except Reoviruses
2) ALL - RNA viruses must code for their own RNA-dependant RNA polymerase (aka virion polymerase)!
3) ALL have are enveloped→ Except- Calciviruses(+ssRNA), picornoviruses (+ssRNA), and reoviruses(dsRNA)- think GI bugs
4) ALL have HELICAL capsids→ Except-
a) Calciviruses, Flaviviridae, Picornoviruses , and togaviruses (+ssRNA)→ Complex
b) reoviruses (dsRNA)
5) ALL replicate in the CYTOPLASM→ Except- Orthomyxoviruses and Retroviruses which also have a nuclear phase
6) ALL +ssRNA viruses have ss, linear, nonsegmented genomes→ Remember retroviruses are diploid +ssRNA
7) ALL -ssRNA viruses have ss, linear genomes→ except Bunyaviridae and HDV (both circular)
8) Arenaviruses are oddballs→ circular ambisense ssRNA
Positive Sense RNA (with prime example): Negative Sense RNA (With Prime Example):
 Calciviridae- Norwalk Virus  Bunyaviridae- Hantavirus
 Coronaviridae- Coronavirus, SARS-CoV  Deltavirus (Unclassed)- HDV
 Flaviviridae- Dengue, HCV, Yellow Fever  Filoviridae- Ebola, Marburg
 Picornoviridae- Cocksackie, Echo, Entero, HAV, Polio, Rhino  Orthomyxoviridae- Influenza
 Retroviridae- HIV, Leukemia & Sarcoma Viruses  Paramyxoviridae- Mumps, Measles, Parainfluenza, RSV
 Togaviridae- Equine encephalitis viruses  Rhabdoviridae- Rabies Virus, Vesicular Stomatitis Virus
Ambi-Sense RNA Viruses: Viroid-like Agents:

 Arenaviridae- Lassa Fever  Hepatitis D Virus
Double-Stranded RNA Viruses:

 Reoviridae- Colorado Tick Fever, reoviruses, Rotaviruses
Prions and Slow Viruses:

 Subacute Sclerosing Panencephalitis Virus
 JC Virus
 Animal Lentiviruses
 Prions
Oncogenic RNA Viruses of Humans:

Retroviruses  Nondefective
 Type B Tumor Viruses  HTLV 1 and 2 viruses
 Bittner Virus (mouse mammary tumor virus)
 Type C Tumor Viruses
 Defective
Vaccine Notes:
A few mnemonics to remember vaccines.
Recombinant Viral Protein Vaccines

" He Bites, He Eats, He Poops!"
 Hepatitis B virus:
 Energix B or Recombivax HB
 Twinrix (+HBV)
 Hepatitis E virus:
 Recombinant Capsid protein
 Human Papilloma virus: (Types 6, 11, 16, 18)
 Gardasil or Cervarix
Live Attenuated Vaccines

"Live, Small, Yellow, Attack Chickens flu the coop at Sabin's MMRket!
Rotavirus free!"
(corrupted from first aid)
 Smallpox: Vaccinia
 Yellow Fever: 17D
 Adenovirus: Retired vaccine- formerly used with military
 Varicella: Oka
 Influenza
 Sabin's Polio virus- No longer recommended
 Measles: Enders
 Mumps: Jeryl Lynn
 Rubella: Ra27/3
 Rotavirus: Rotarix and RotaTeq
Killed Virus Vaccines

"Always RIP if killed" (again first aid)
 Hepatitis A virus: VAQTA or Havrix or Twinrisk (+HBV)
 Rabies virus (human diploid cell)
 Influenza:
 Polio: Salk
Pooled Gamma Globulins

"Harry Always Hated Buying Ralph's Very Rotten Muffins."
Passive Immunity.
 Hepatitis A Virus
 Hepatitis B Virus
 Rabies
 Vericella
 Rubella
 Measles
DNA Viruses:
Naked DNA Viruses:

Adenoviridae:
 49 Human serotypes
 DNA and 12 protein icosohedral capsid of 252 capsomers (240 hexons and 12 pentons)→ NO envelop
 Penton→ base, fiber and knob
 Dense nucleoid core→ linear dsDNA w/ prot at 5' end of each strand→ pseudocircle
 Grouped on: DNA base composition, Oncogenic properties, and hemagglutination
 Cell interactions:
 Lytic in tissue culture→ multiply in host cell (some prod latent infxn- tonsils, adenoids, lymphoid organs)
 pH stable but heat labile
 Small % resp dz but some serotupes cause large % URD (5-50%)
 Oncogenic to lower animals
 Replication:
 parental viral DNA→early mRNA→ early prot→ prog DNA rep→ late mRNA→ Late struct proteins→ prog virions→ release (not lysed)
 Early enzymes- for DNA synt- thymidine kinase and DNA polymerase→ "Grape-like" clusters in nucleus
 infections:
 preference for conjunctive, resp and intestinal epith, and regional lymph nodes
 Types 4,7,3,11,14,21→ acute resp Dz (14 cause a severe form)
 Types 8,7,19, 3→ Keratoconjunctivitis (SHIPYARD CONJUNCTIVITIS)
 Types 7, 3 → Pneumonia in children (may be fatal)
 Types 2,5→ Pharyngitis in children
 Neut Ab persists 8-10 years
 Vaccine→ types 4,7→ possible oncogenic potential?
Parvoviridae:
 Dependoviruses (need helper virus) and Erythroviruses (B19- rep in actively dividing cells)
 B19→ slapped cheek/ fifths Dz→ Smallest human viruses (ssDNA no ENV/ icos capsid)
 3 protein capsid and 2 nonstruct prots→ genome replication→ requ actively dividing cells
 Transmission via resp droplets
 If primary in first months of pregnancy→ fetal infection (5-10% death) or HSmegaly and anemia→ fetal hydrops
 Immunity→ 50% population has Ab's
 Dx→ IgM for Erythrovirus B19 and NAA of fetal blood for B19 DNA
Erythema Infectiosum
 "Fifth Disease"← SLAPPED CHEEK appearance
 Parvovirus B19
 Replication in erythroid precursors
 Spread via resp secretions (usually ages 4-10yo)
 Clinical:
 Arthralgia common in adults
 Slapped cheek rash in kids
 Eruptions of erythematous mac/paps on ext surf of ext, trunk, neck→ becomes confluent lacy and reticulated
 Complications:
 aplastic crisis in pts w/ chronic anemia/imm-comp (sickle cell)
 1º infxn during preg→ nonimmune fetal hydrops and fetal demise

 Treatment: Supportive therapy (self limited/ no specific antivirals)
Polyomaviridae / Papillomaviridae
 Papova→ Papilloma/Polyoma/Vacuolating (SV40- studied extensively)→ DNA virus- capsid
Virus/Host- SV40
 Two infection types→ Lytic or Transformative
 Lytic→
 SV40 binds receptor→ enter cell→ uncoats particle releasing circ dsDNA into nucleus→ Transcript early T and t antigenic proteins
 T and t are regulatory proteins→ bind viral DNA→ init DNA replication→ new genomes transcribed into mRNA→translate to late
capsid proteins
 Virus assembles→ cells lyses→ progeny released NO ENVELOPE!!!
 Transformation
 Same initial steps but only early events occur
 Viral genomes integrated into host cell DNA→ only transcribe and produce early mRNAs→ t and T Ag's
 T- antigen assoc w/ p53 and p110-Rb and the RB gene product
 T and t Ag's→→ loss of contact inhibition, ↓ GF requirements for prolif, may cause tumor
 Transformation requires non-permissive cells→ lyric requires permissive cells
 Papovavirus→ (JC virus→ Progressive Multifocal Encephalopathy (PML) esp in AIDS ) and (BK virus→ hemorrhagic cystitis)
HPV- Human Papillomaviruses

 Predilection skin and mucosa→ no viremia (direct skin contact)
 Viral proteins E6 and E7 bind p53 and p110Rb respectively
 40types of anogenital tract thru intercourse→ HPV 6,11,16,18
 HPV 1 and 4→ PLantar warts
 HPV 2,3, and 10→ knees and fingers
 Infect basal layer of skin but viral replication only occurs during differentiation→ form warts/papillomas
 Skin/Genital Papillomas→ cerival dysplasias (6,11,16,18)→ potential cancerous transformation (sun exposure ↑ risk of sq cell ca's)
 Latent infections→ DNA can remain in basal layer cells→ Imm-comp can reactivate→ crops of warts
 treatment→ Skin papillomas w/ podophyllin; Cervical dysplasia w/ laser/cryosurgery
 Prevention→
 Vaccine (Gardasil)→ QHPVV→ HPV L1 protein (Major Capsid protein) from 6,11,16, and 18 (plus Al adjuvant)
 L1 gene engineered into yeast vector→ yeast produce non-infectious virus-like particle
 Vaccine schedule→ 0,2,6 months at age 11/12 but early as 9 (catchup 13-26yrs)
 Dx→ NAA for type and virus load
 HPV→ 5% get low-grade sqamous dysplasia; 10% progress to high grade SIL's and poss Ca
 Types 6 and 11→ mild dysplasia - low-risk types
 Types 16 and 18- High Risk; Types 31,33,35- Mod risk→ High-grade dysplasia
 90% cerv cancer assoc w/ 16,18,31,33,35,39,45,51,52,56,58,59,68
 t16- 80% vulvar cancers
 50% vaginal/penile cancers→ HPV
 35X ↑ in anal cancer w/ MSM
Enveloped DNA Viruses:

Hepadnaviridae:
 Hepadnaviridae→ partially dsDNA→ Dane Particle --- core(HBcAg) and envelope(HBsAg)- HBeAg→ infectivity
 42nm DANE PARTICLE (infectious particle)→ 22nm (HBsAG aggs) and 27nm (Core) particles not infectious
 partial circular dsDNA with a reverse transcriptase complex
 Surface Ag (HBsAg)→ 22nm sphere or 22x200nm rod and contains several determinants.
 Group specific antigen- "a"
 Subgroups: d or y PLUS w or r→ adw (asxs carriers), ayw (dialysis and druggies), adr, ayr
 Core Ag (HBcAg)→ 27nm found in liver- IS NOT INFECTIOUS
 -e Antigen (HBeAg)→ infectivity antigen
 Replication→ nucleus AND cytoplasm
 attachment→ entry→ uncoating→ partial DNA genome converted to full dsDNA via DNA polymerase
 dsDNA→ transcribed into viral RNA→serves as mRNA and template for genome DNA synthesis(via reverse transcriptase)
 RNase H degrades RNA stand of full RNA-DNA→ DNA polymerase copies the full-length strands
 Progeny virus enveloped by a lipid bilayer and ass/w HBsAg's
 Disease
 Most people w/ limited infection (some go on to produce chronic infection)
 LONG INCUBATION→ gradual onset→ MOST RESOLVE (few progress to persistant or chronic active Dz)
 Epidemiology
 Virus in blood/bodily fluids→ ↑ incidence in parenteral drug users, MSM, infants to HBV+ mothers
 Lab Dx→ EIA (measures HBsAg or anti-HBsAg)- measuring levels can determine stage
 Immunity→ LONGTERM→ partial immunity to all subtypes d/t "a" determinant
 Ab's vs HBcAg first (IgM followed by IgG)→ HBsAg (resolution stage)-IgG vs HBsAg NOT MADE in chronic infection
 Immune complex formation may lead to necrosis of liver via vasculitis
 Px and Control:
 pooled gamma globulin HBIG only protective if given immediately after exposure
 Given IM to newborns of infected mother + vaccine ASAP
 Monitor blood banks
 Original vaccine→ 92% effective and protect vs liver cancer (Heptavax preferred if yeast allergy)
 Heptavax- adw subtype
 Recombivax and Energix B→ HBsAg produced in yeast (expensive AND effective)
 Comvax→ H. Flu B and Hep B vaccines
 Twinrix→ Havrix +EnergixB
 Pegylated Alpha interferon→ ↓ effects if ↑ level of viremia (reduce load volume)
 Nucleoside Analogs→ Lamivudine, entecavir, adefovir (for persistant and chronic infections)
 HBV linked w/ primary hepatocellular carcinoma (200x↑)→ HBV-DNA integrated into cell DNA
Herpesviridae:
Replication (Ex: HSV)
 Rolling concatomer process→ IN THE NUCLEUS
 Four DNA configurations- alt arrangements of Us and UL strings
 Prototype (P), Inverted Short (IS), Inverted Long (IL), Inverted short and long (ISL)
 HSV receptor→ possibly heparan sulfate
 Linear DNA circularizes→ Multi genomes cleaved at unit lengths→
 immediate early mRNA (α- reg proteins)→early mRNA (β- enzymatic proteins)→ late mRNA (ƴ- Structural proteins)
 enzymes→ DNA-dep DNA polymerase and thymidine kinase (target of acyclovir)
 Nucleocapsid formed from struct proteins→ Capsid envelope acquired when budding through nuc membrane
 CPE→ Cell DNA pushed to edge of Nuc membrane→ SHUTS OFF CELL SYNTHESIS→ Cell death & Syncytia formation
Herpes Simplex Virus (HSV) 1 & 2

 Herpesvirus (enveloped dsDNA virus)
 Lytic/Persisant and latent infxns (lifelong infxn/source)
 Enters abraded skin/intact mucosa →Repl in fibroblasts and epithelial cells (latent→neurons)
 Clinical
 vesicles on erythematous base (dewdrop on rose-petal)→ painful and recurring
 HSV I (90% oral)→ Gingivostomatisis
 HSVII (90% genital)→ Can infect brain of neonates→ follow oldfactory nerve to temporal lobe
 1º eruption larger and more severe than 2º
 1º infxn→ fever, lymphadenopathy, malaise (potential for neonatal Dz from maternal genital lesions)
 Congenital infection→ Fetal CNS and Liver- prevent w/ cesarean
 May disseminate in Imm-supp'd or Malnourished
 recurrence lim. to mucocutaneous area of latent nerve→ prodrome of tingling/burning/pain
 trigeminal ganglia or sacral ganglia- episomal latency
 Gingivostomatitis, Herpes Whitlow (knuckles), Dendritic Keratitis, Gladatorium (knee/elbow), eczema herpeticum
 May present as erythema multiforme
 Eye infections→ Primary and Recurring- dep on strain and host health→ infx stromal layer of keratocytes and collagen
 Primary→ epith cells- dep on strain- some cause dendtritic ketatitis
 (seen w/ fluorescent dye and blue light or Rose Bengal or via a slit lamp microscope)
 Some strains→ geographic ulcers
 Stromal ulcers possible→ recurrent infections→ loss of visual accuity
 CORNEAL MELTING→ most severe form→ may have imm part- PMNs, MQs, and T-cells cause damage
 corneal transplant may repair, but infection may recurr
 Diagnosis
 Direct Mic→multi-nuc giant cells on Tzanck smear
 Cell culture
 PCR (1vs2)
 Serology is only for epid. studies
 Treatment: Antivirals (acyclovir, valacyclovir)
 Herpetoviridae→ dsDNA Linear→ Env and Icos capsule
 Cowdry Type A inclusions or cause cell rounding and polykaryocyte formation
 Rep in nucleas→ env w/ nuc budding→ early and late stage enzymes→ replication via rolling circle- concatemers formed
 Produce viral-specific thymidine kinase- target of acyclovir
 Genital Infections:
 HSV-2 mainly- oral sex→ HSV-1
 Incubation Time→3-7days→ vesicles to ulcers w/ regional lymph swelling (HA/F/Malaise)→ heal in 2wks
 Latency→ migrate to sacral ganglia→ react w/ imm system changes/radiation/chemo/stress
 Dx→ IF w/ spec Ab's AND Typing VIA HSVDNA methods
 Tx→ Nucleoside analogs→ acyclovir(IV for systemic infxns and prodrom stage)/valacyclovir/famciclovir
 Inhibit DNA polymerase (foscarnet/trifluridine/vidarabine) or stop DNA chain elong (acyclovir/pencyclovir)
Varicella (VZV)
Herpesvirus 3
 Congenital infections→ primary infection in first trimester→ malform limbs and muscles→ CNS dfx
 Primary infxn during preg can present w/ abnmls in newborn or childhood
 Latent infxn → RARE fetal infection
 HSV May also infect during birth canal travel→ perinatal infection
Acute-Chickenpox/Recurrence- Shingles (herpes Zoster)
 Herpesvirus (dsDNA)
 90% transmission rate (respiratory rte)→ viremia
 ↑ Recurrence rate in imm-supp and elderly
 Clinical:
 Vesicular rash (usually pruritic) in crops:
 Centripetal => Macules→papules→vesicles & crusted papules (d4 stops, d6 crust/healing)
 herpes zoster ophthalmicus→ latent infection in trigeminal ganglia→ keratoconjunctivitis, uveitis and optical nerve palsies
 Treatment
 Acyclovir and Ig for Imm-Comp (antivirals shorten rash is started w/n 72 hrs of onset)
 Varicella Vaccine for age 1 (2 doses)
 Complications:
 2º bact infxn, encephalitis, Pneumonia
 Congenital infxn (1st 20wks of preg),

 low birth weight, mental retardation, seizures, GI/GU/Skel probs, dermatomal hypoplasia
 Shingles: Herpes Zoster
 Recurrence, Rash in single, unilateral dermatome
 Prodrome- burn/itch
 Eruptive phase similar to chickenpox
 Sxs:
 Herpetic Neuralgia (typ- 4-5 dys prior to erup), F, HA, malaise (neuralgia may remain)
 2/3→ thoracic region
 Treatment:
 Antivirals: ↓ pain, inflam, vesicle formations and viral shedding (acyclovir/valacyclovir)
 MANAGE PAIN
 Zoster vaccine is over 60yo (1 dose)
Epstein-Barr Virus
Herpesviridae Lymphocryptovirus: Herpesvirus 4
 replication in lymphoblast cell lines→ CD21+ cells (Complement factor C3d) →serves as virus receptor on B cells and Epith cells
 MAY activate MYC proto-oncogene→ lymphoma
 Viral Antigens:
 EBNA (binds DNA), VCA (capsid), MA (membrane), EA (early Ag)
 No relation to other HHV's
 Hosts→ limited to humans and non-human primates
 Cell interactions:
 Permissive cells→ B-cells and Epith cells→ support EBV replication
 Latent infection→ B-Cells if competent T-cells are present
 EBV/B-cell interaction is different
 EBV Genoma circularizes into "plasmid"→ replicates as cell does→Ag's include EBNA and LP's (both bind DNA)
 Immortalization→ of B Cells (↑ prolif)
 LMP's stim B-Cell replication and promote immort
 Replication Notes:
 Ability to synth 70 proteins
 Late proteins gp350/220→ glycoproteins for receptor docking
 Assoc. Dz's
 Burkitt's Lymphoma→ Africa- may have malarial cofactor
 Infectious Mono→ Atypical lymphocytes (Downy Cells/ Large T-lymphocytes)
 Lymphadenopathy/ Splenomegaly/ Exudative Pharyngitis
 Chronic→ fatigue, fever, HA, Mental Lapses, Numbness, depression
 Heterophile Ab's→ agg RBC's of nonhuman origin→ 60-80% +; Other Ab's; Atypicals
 Dx→ Monospot test (IgM heterophile Ab's- diff from CMV if Neg); Downey Cells;
 Infxn Course: VCA (IgM)→ VCA (IgG)→ EA + EBNA Ab's
 Oral Hairy leukoplakia→
 Nasopharyngeal Carcinoma→ ↑ incidence in males of chinese extraction
 EB genome in epith cells→ if T-cell deficient then B-cell leukemia/lymphoma may dev

CMV
Herpesvirus 5
Primary or react'd latent
 If primary→ 40% infection rate of fetus (preg time may not be important)
 95% CMV infections during preg are asxs
 Larger genome than other HHV's→ has dsDNA in addition to mRNA
 replication:
 Infx fibroblasts, epith's, MQ's→ 4-6wk incubation before CPE
 Latent infxn poss in BM and monocytes
 Dz Assoc:
 Fem w/ ↓ T-cell response→ ↑ rate of fetal CMV infection
 Fetal CMV syndrome- primary infxn→ Hearing loss/MR/Eye defx/ HSmegaly/thrombocytopenic purpura
 Reactivation CMV (3rd trim)→no abnml's - late in dev and pre-existing Ab's
 CMV in HIV→ retinitis; CMV in Tranplant/transfusion Pts (3-4 weeks after→ big cause of kidney failure)
 CIDz→ Cong infection of visceral organs→ death, jaundice, spleen comp's, TTP chorioretinitis, Rash #1 congenital infection
 Most infections are subclinical
 Dx→
 Isolation from urine and saliva for culture
 Anti-CMV IgM levels in newborn serum/ NAA for viral DNA in blood and urine imm after birth (isol from throat/urine possible)
 Owl's Eye inclusions→ Heterophile negative mononucleosis
 Tx→ NOT ACYCLOVIR→ ganciclovir, cidofovir
HHV's
 HHV-6
 Roseola infantum (exanthem subitum/ sixth Dz)→ Infx B and T cells, epith, endoth, and neurons→ hi lvl in saliva
 Acute febrile illness w/ or w/o rash (fever, fuzziness, rhinorhea)→ poss. rash in 3-5 days as fever abates (centrifugal)
 HHV-7
 Ubiquitous→ HIGH FEVER (103-105) and rash
 95% adults are seropositive (ass. w/ pityriasis rosea)
 HHV-8
 Implicated in Kaposi's Sarcoma
Poxviridae:
Molluscum Contagiosum
 Poxvirus: Molluscipoxvirus
 Clinical: Usually benign w/ no systemic manifestations
 Dome-shaped, umbilicated papules→ usually trunk/face/neck
 Children/Young Adults
 Direct Contact spread
 Treatment: (curettage or cryotherapy)
 Genital lesions to ↓ spread to sexual contacts
 Non-genital lesions for cosmetic purposes
Chordopoxviridae:
dsDNA→ core, lateral bodies, inner lipid membrane (Self-synth), surface tubules, outer lipid membrane
Orthopoxvirus:
 Vaccinia; Variola; Cowpox, Monkeypox
 Variola→40% mort
 Vaccinia→ vaccine for smallpox
Molluscipoxvirus
Molluscum contagiosium virus
Small Pox
 Largest and most complex aninmal virus→ oval/brick shapes w/ dumbell inside
 dsDNA→ 3
 major structures: envelop (tight fit and ether resist); biconcave core; lateral bodies
 Enzymes: w/n core
 CORE→ can accomodate extra DNA genome (artif/nat added) of 25kb→ idea bioweapon
 Vaccinia→
 Culture in embryonated hen eggs and tissue culture
 Usually cultured in chirioallantoic membrane of chick embryo→ pocks
 Replicates entirely in Cytoplasm!
 Guarnieri bodies→ eosinophilic cytoplasmic inclusion bodies (viral rep)
 Stage I- Particle attch and enter cell via viropexis
 Stage II: uncoating

 1→ Host cell enzymes remove outer envelope and lateral bodies (act of core enzymes)
 Core enzymes synth viral mRNA using VIRAL DNA-RNA polymerase→ immed early mRNAs→imm early prots
 2→ imm early proteins from virus uncoat and release DNA into cytoplasm
 Stage III: Early events:
 Uncoated viral DNA trans into early mRNA's→ enz activities (DNA Dep DNA polymerase; thymidine kinase; exonucleases)
 Stage IV:
 DNA rep in defined areas (inc bodies)→ progeny DNA
 Stage V:
 Progeny DNA trans into LATE mRNAs→ structural proteins
 Synthesize one layer of their own envelop and acquire other through cell membranes
 Stage VI:
 Mature and assemble→ progeny particle accum in cytoplasm → microtubules move virus to surface for egress
 Disease:
 1- Upper resp entrance as aerosolx→ multi in resp mucosa and regional lymp nodes
 2- Transient viremia→ spread and rep in internal organs and marrow→ into blood
 3- VIREMIA→ skin (face first)→ centrifugal spread ex/enanthem
 Long inc period (6-17days) allows vaccination (best w/n 4 days)→ blocks infection
 Severe fever 1-4dys before rash >101F→ VERY IMP Prodomal symptom
 RASH: macule→papule→umbilicated vesicle→ pustule→ crust and scar (STILL INFXOUS)
 Palm and sole rash→ synchronous eruptions symmetrically
 Variola evades Imm system via synth of IFN binding protein
 Guarniei bodies: eosinophilic Cytoplasmic inclusions→ presumptive for PV (IMA for SPV ag's and later time spec Ag's)
 ONLY FOUND IN MAN!! Reason for eradication
 Spreads person-person (but not easily w/ some exceptions
 Not infxous during incubation or first day of prodrome
 IS infxous from rash onset to crusting (Scabs may contain virus); Upper resp secretions contain virus
 partially immune w/ few lesions that escape detection are MOST contagious
 Ruptured pustule > inf than crust
Bioterrorism- currently complication risk> smallpox risk
 May go undetected for 2.5 wks
Vaccine
 Vaccine!→ most important in Px and control→ Live attenuated virus
 First gen: from calf-lymph- long shelf-life 1/5 conc
 Second Gen vaccine: Tissue culture produced vaccine by orovax for bioterrorism
 Third gen: MOd'd vaccinia ankara→ more avirulent but still bein assessed
 Responses:
 Primary response→ same lesion prog as actual smallpox→ ind no prior imm (8-10dys)
 Accellerated response→ Partial immunity- 3-7dys
 Early/Immed response→ Hypersensitivity→ imm not certain (2-3days)
 Ab imm developed 8-10 days after vacc (Why best if given w/n 4 days of exp)
 New recomb DNA vaccines employ vaccinia virus (Op-site patch occlude lesion)
 Still need to dev truly atten vaccine (still complication risks)
 Bifurcated needle→ 15 inocs into dermis/epidermis
Vaccine complications:
Vaccinia Gangrenos:
 Spreading lesion w/ necrosis of skin/muscle
 In those w/ thymic dysfxn (T-lymphocytes!!!)→ AIDs w/ vaccine→ fatal Dz
Generalized Vaccinia:
 W/ agammaglobulinemia or normal children→ oft fatal (resembles generalized herpes infection
Eczema vaccinatum
 Localized vesicles in area of acne/eczema
Fetal Vaccinia:
 Vaccine of mother→ fetus still births or recovers
Pastvaccinal encephalitis:
 hypersens or viral invasion of CNS→ sudden onset @ 12day
 Often fatal (not in inf <6mos w/ maternal Ab's)
 25-30X more in adults (demyelination/pleocytosis)
 Susceptible adult population is vaccination prog restarts
Notes:
 Vaccinia Immunoglobulin admin'd to some imm-comp individuals w/ vaccinia infections (primary Tx)
 Chemo:
 Cidofovir: inh viral DNA polymerase (Secondary Tx)
 S-adenosylhomocysteine Hydrolase inhibitors
 Rifamicin: inhibit viral morphogenesis→ Blocks proteolytic cleavage of precursor proteins into smaller prots
RNA Viruses:
Positive Sense RNA

Calciviridae
 +ssRNA, Icos Capsid, nonsegmented, NO ENVELOPE
Noroviruses (Norwalk Virus)

 G1 and G2 genotypes
 Infectivity:
 Only small number of viral particles required (<100)
 prolonged shedding (2wks after recovery)
 Resistant to alcohols and detergents, stabl to environment
 Long lasting immunity is not developed (short lived IgA)
 Infection:
 Blood Group ABO glycolipids/glycoproteins act as cell surface receptors
 Blood Groups B and AB may offer some resistance d/t poor binding
 Fx all ages→ N, Ab pain, V, D, Chills, HA, Myalgia, Fever
 Epidemiology:
 Major cause of worldwide nonbact/nonparasitic gastroenteritis→ spread via fecal-oral route
 Peaks in winter months (winter vomiting disease)→ ↑ in close quarters or communities(CRUISE SHIPS/ DORMS/ BARRACKS)
 Dx→ ELISA, RT-PCR, electron microscopy
Hepatitis E Virus
 Hepevirus genus- four genotypes
 Transmitted via drinking water, from pigs (possible zoonoses)
 Very serious infection in PREGNANT WOMEN*****→ 20% fatality rate
 Outbreaks primarily in urban areas of developing countries or rural areas of developed one
 LIFETIME IMMUNITY with no carrier state
 Dx→detection of anti-HEV IgM during acute infection
Coronaviridae
 morph similar to -ssRNA viruses BUT is +ssRNA (poly A 3' termini), Helical nucleocapsid
 Capsid→ two glycoproteins in envelope→ form peplomers
 Replicate in cytoplasm, envelope via budding- use Polio replication as model (RI formed)→ little/no CPE in TCx
Coronavirus
 Group 1 (Human coronavirus NL63 - New Haven); Group 2 (SARS-CoV)
 Hosts→ humans, rodents, wild animals
 Diseases:
 Infxn Bronch of humans (IBH)- mainly adults; Cold, Pharyngitis, usually afebrile
 SARS→ Lower Resp tract infection
 high Fever, SoB Cough→ spread via cough/sneeze/close contact→ inc in 2-7 days
 Binds cell receptors for Angiotensin-converting enzyme 2 (ACE2)
 Appears to be variant derived from virus found in wild animals
 Gastroenteritis: Strain determines severity- infx humans and rodents
 Possibly causes gastroenteritis in infants→ NECROTIZING ENTEROCOLITIS in newborns
 Dx→ PCR and serology
 Tx→ Vaccine in development
 Px→ QUARANTINE PROCEDURES
Flaviviridae
 +ssRNA, icosohedral Capsid, Envelop, NON-segmented
Flavivirus:
 Similar to togaviruses and PROTEASE RESISTANT
 ARBOVIRUS
 Clinical:
 First Stage: insect bite and virus into blood stream→ Replication in RE system→ viremia with F/C/M/V
 Second Stage: Virus invades tissue→ encephalitis (S. Louis, Japanese, West Nile) from crossing BBB
 Flavirviruses infect multiple systems:
 skin and endothelial cells as well as various visceral organs
 Causes hemorrhagic fever, yellow fever virus and dengue fever viruses can cause severe clinical disease
 Yellow Fever Virus:
 Second stage→ very severe saddle back fever (Diphasic), necrosis of liver (jaundice/ yellow) and kidney
 hemorrhages occur in stomach→ RBC + stomach acid= BLACK VOMIT of yellow fever
 Dengue Virus (4 Serotypes)
 Dengue Fever→ BREAKBONE fever
 less severe→ mac-pap rash, pain in joints and muscles, possible ocular pain and saddle back fever
 Severe→ May progress to hemorrhagic fever (DHF) and possibly to SHOCK syndrome
 Shock syndrome→ 1º infection by serotypes 1,3,4 then 2º infection by type 2
 Ab-Ag activates monocytes→ ↑ cytokinda→ immunopathology
 Accomp by hemoconcentration (↑in F) then thrombrocytopenia (hematocrit and plt counts)
 Treat w/ acetominophen to avoid anticoag of aspirin, hydratio therapy for hemoconcentration
 Can induce less severe disease w/o hemorrhagic fever
 Hemorrhagic fever occurs when virus infects skin, muscle, and viscera
 Flavirvurs encephalitis
 West Nile virus→ insect vector (animal reservoir), blood transfusions, organ transplants→ viremia thru BBB→ CNS
 Lab Dx of WNV (isolation is not practical)→ serology detects acute and convalesent sera using CF Ab's
 Px and control→ YF, DFV and Encaphalitis
 Eradication of vector population→ BUG spraying, breeding site destruction
 Yellow Fever→ Immunization via 17DD or 17D 204 vaccines (LAVV's) -imm may cross over to WNV
 Vaccine also available for Japaenese encephalitis
 No vaccines for DFV.
 Horse vaccines to ↓ reservoir
 Epidemiology:
 Imported yellow fever virus from global travel- typically limited to vector flying range
 If Dx'd with yellow fever→ QUARANTINE
 Encephalitis viruses a concern of bioterrorism
Hepatitis C Virus:
 Hepacivirus→ Transmit via blood/blood products→ 35-70day incubation (IV Drug Use is primary mode of transmission)
 50% progress to chronic active liver disease→ 10-20% show evidence of biopsy
 Milder symptoms than HBV, less jaundice, lower transaminase
 Discovered→ Blood screening to HBsAg led to elim of HBsAg+ Blood but infection remained→ volunteer blood banking system
 Dx→made for HCV thru molec biology
 EIA (circ ab's)→ Confirmatory tests via nucleic acid tests or immunoblot test
 Risk→ IVDU's, Hemodialysis, whole blood products
 Tx:
 Alpha-IFN (peg)→ beneficial to some pts but ↑↑ relapse rate when tx is d/c
 ±ribavirin→ good response vs genotypes 2 and 3 (1 is resistant)
 Polymerase inh's and Protease Inh's (telaprevir and boceprevir)→ in development
 May cause PHC
Picornoviridae
 +ssRNA, nonseg'd, Genome can transfect cells
 RNA has poly A at 3' and VPg at 5' end
 Capsid has 4 proteins→ VP1, VP2, VP3, VP4 (icosohedral w/ no envelope)

 Enteroviruses acid stable, rhinoviruse acid labile
Enteroviruses (acid stable)

 respiratory and intestinal dz
 Overt Dz mainly in young, elderly and imm-supp'd
 *New* Enteroviruses
 Type 70→ acute hemorrhagic conjunctivitis
 Type 71→ paralytic Dz/ encephalitis
 Type 72→ Hepatitis A Virus
Hepatitis A Virus
 Enteroviruses Type 72
 +ssRNA, 27nm particle, very resistant and acid-stable- ICOS CAPSID and NO ENVELOPE
 Clinical:
 Sporadic outbreaks, short incubation, no carrier state, low mortality
 Children have mild disease, Adults are more sever→ esp post-menopausal women and those w/ chronic liver disease
 Fecal-oral route→ function of hygiene (↑ in mental institutions, day care workers, male homosexuals and poor)
 HIGH viral load in feces
 Multiplies in GI tract epithelium and Lymph nodes→ viremia→ liver, kidney, spleen
 virus present in feces, urine, blood during pre-icteric stage
 Course→ 2-8wks→ Pre-icterus and infectious→ acute infection only
 Vaccine→ steady ↓ since introduction→targetted to high risk adult pops (HAVRIX or VAQTA→ +Ab's in 93%)
 Twinrix→ HAV and HBV
 Pooled gamma globulin also available
 Dx→ Immune EM detects virus→ Anti-HAV IgM elevated
 Immunity is long term and HAV specific
Coxsackieviruses
 Group A (23 types):
 Vesicular pharyngitis (herpangina)→ posterior enanthem (HSV- lesions are througout oral cavity)
 Summer Grippe, frebrile illnes, Colds, Hand/Foot/Mouth Dz ( rash on palm/soles)
 CA24 and enterovirus 70→ acute hemorrhagic conjunctivitis in tropics
 Entervirus 71→ HFM Dz + high rate of CNS compl's
 Aseptic meningitis (Stiff neck/back, nausea, HA, abdo pain, fever, virus in CNS
 Petechiae/rash may occurw/ meningitis; Full recovery unless complicated by meningoencephalitis
 Non-polio enteroviruses= leading Infxn for aseptic meningitis in US (>80%)
 Group B (6 types)
 Epidemic Myalgia/Devil's Grippe; Aseptic Meningitis,
 Neonatal Dz→ 1º pericardial/myocardial Dz, Cyanosis, tachycardia, dyspnea
 Possible link to TYPE 1 Diabetes
 Dx→ Isol from throat>Feces>CSF; OF; RT PCR; Neutralization Ab; VIRUS POS IN CSF
ECHOViruses:
 Summer aseptic meningitis (type 11)→ Virus + in CSF (RT PCR for Dx)
 Summer epidemics of febrile illness w/ rash (esp in young)→ VIRUS POS IN CSF
 Nonbact diarrhea
Poliovirus
 Serotypes: 1, 2, 3
 Massive vaccine campaign has ↓↓↓↓↓↓ incidence in US
 3 major reservoirs left→ Pakistan/Afghanistan; Northern India; Nigeria
 Sabin (live)→ risk of reverting to neurovirulent strain → 3 doses
 Salk (killed) currently recommended→ 4 doses
 Infxn Route→
 Tonsilectomy (exposed nerves)→ CNS→
 Peyer's Patches of alimentary canal→ lymph nodes→ viremia→CNS→
 Both lead to cerebellar/Vestibular nuclei and anterior horn of spinal cord

 Infection types:
 Inapparent Infections→ Young individuals (90%)
 Abortive Poliomyelitis→ F/M/HA/V/Sore Throat (5%)
 Nonparalytic CNS disease (aseptic meningitis)
 Stiffness and pain in neck/back→ crosses fenestrated vessels endoth in choroid plexus (1-2%)
 Paralytic
 Spinal, Bulbar (back of neck, pons, medulla) flaccid paralysis→ changes in voluntary muscles
 ↑ rate in teens/ young adults (0.1-2%)
 No sensory loss
 Outcomes→ full recovery, residual paralysis, death
 Factors affecting Dz→ Serotype, Infxn dose, Tissue specificity, portal of entry, Age, gender, health, pregnancy
 Replication→
 Attach to PVR→ lose VP4→ Uncoated (lose VP1,2,3)→ RNA genome released (serves as mRNA)
 Translation→ viral polyproteins formed→ polyprotein P123→ P1 + P2 + P3
 P1→VP0 + VP1 + VP3 then during maturation VP0→ VP2+VP4
 P2→ Proteases
 P3→ VPg + 3D (polymerase + Hf)
 +RNA w/ VPg→RNA for replication; +RNA w/o VPg→mRNA for translation
 Lysis is end of cell infection
 Dx→ ↑ leuks (not PMN's); ↑ protein in CSF; Serologyl; Viral isolation from rectal/pharyngeal swabs NO VIRUS IN CSF
Rhinoviruses
 Acid Labile- nasopharyngeal isolation only
 URI- cold/rhinitis→ over 100 serotypes, 2-4d inc, lil/no fever→ immunity transient and via short-lived IgA (and little crossover)
Retroviridae
 Helical nucleocapsid PLus Icosohedral or cylindrical outer capsid→ env via budding
 Genome is diploid 35S ssRNA joined by specific tRNA's
 Enzyme Complex→ Rev Transcriptase, DNA polymerase, and RNase H (with proteases and integrase coded by "pol" gene
 Genes:
 ENV→ 3 envelope prots
 GAG→ 4 internal capsid proteins
 GAG-Pol-Env±ONC gene (acute leukemia/sarcoma viruses usually LACK Env but are ONC+)
 For HIV→ GAG-POL-ENV+ Nef, tat, rev, VIF, VPU, VPR
 transcription→ 3 mRNAs (35s- gag or gag-pol, 28s, 21s- ONC prot)
 HTLV→ Human T-lymph Virus
 HTLV-I → ass/w Adult T-cell leuk/lymph (ATL) and tropical Spastic Paraparesis (TSP)
 ATL→ Malig of mature T-lymphs; Found in japan, caribbean, Africa; Peak from 40-60
 TSP→prog diff walking, sens disturbances, urinary incontinence
 transmission via cellular components of blood- NOT PLASMA
 FDA does have approved HTLV-1 test
 HTLV-2→ Poss rel/w hairy cell leukemia
 Oncovirinae→ Tumor Viruses
 Lentivirinae→ slow viruses
 Spumaviruses→ Human Foamy retroviruses
 Chronic leuk viruses→ lack ONC but activate cell protooncogene
 Acute Leuk/Sarcoma→ lack ENV but possess ONC (except Rous Sarcoma- has ALL genes)
 LTR's→ conversion of RNA to DNA provirus leads long terminal rpt's at end of provirus w/ reg regions
 Normal DNA tumor virus- transform OR lyse→ Retrovirus- transform AND lyse
HIV (and LAV)→

 HIV-1→ widespread serotype
 HIV-2→ primarily in W. Africa (STLV→ infects old world monkeys; HIV-2 is related to SIV and STLV)
 HIGH mutation rates d/t Reverse transcriptase
 HIV→ changes tropism over time: Initially M-Tropic (MQ's) then T-Tropic (CD4+ T's)
 genome:
 GAG→ Capsid; POL→ enz complex; ENV→ gp160= gp120+gp41

 TAT→ Transcription transactivator: Has promotors for viral and cellular reg regions
 REV→ Regulates transport of mRNA into cytoplasm from nuc
 Tat and REV mRNA→ synth as result of multi splicing events
 NEF→ ↓ expression of CD4 and MHC1 (req'd to acheive HIGH viral load)→ key for full blown AIDS
 VIF→ ↑viral assembly and blocks cell APOBEC-3G
 VPU→ ↑ release of virus from infected cells→ inh CD4 surface expression
 VPR→ Arrests cells in G2 phase of cell cycle
 Structure Proteins:
 Diploid ssRNA's bound by p9/p7
 Cylindrical core of p24 (rev trans is in core)
 Outer env→ p17
 ENV glycoprots→ gp160 (distal gp120, prox gp41)→ MAJOR VIRAL Ag's- ↑↑↑ Ag variation
 GP120→ receptor attachment
 GP41→ env to cell membrane fusion (CCR5 co-receptor- M Tropic; CXCR4 coreceptor- T- Tropic)
 R5 init infxn→ X4 progresses infxn
 replication:
 Env/CM fusion→ uncoating→ Rev-Trans RNA moved to nuc→ provirus integrated and activated
 Imm virus buds to form envelop→ GAG and POL are cleaved to form mature viruses
 Kaposi's Sarcoma→TAT transactivator, HHV-8 Cofactor
 AIDS→ CD4+ below ~200
 Flu-like/Mono type sxs→ asxs period→ARC (fever, NS's, wt loss, PGL)→ AIDS
 AIDS→ Diarrhea, Dementia, 2º infections, Cancers
 p24 ↑ in 1º infection→ ↓p24 as sxs decline and anti-p24 ab's ↑
 CD4+ <400→ thrush, shingles, EBV (oral hairy leukoplakia)
 CD4+ <200:
 Pneumocystis Carinii, Toxoplasma Gondii, Mycobacterium Avium, Cryptococcus Neoformans, Histoplasma/Coccidio
 Viral→ CMV, HSV, PML (papovavirus), EBV
 Cells infected by HIV→ MQ's (latent) and T-helpers ( latent or destructive), cd4+ B-cells (minor); Dendritic cells→ reservoir
 ↓ CD4+ T-helpers→ ↓Delayed Type (IV) hypersensitivity
 Dx→ HIV Ab's Screen→ ELISA→ Western Blot (+→ bind gp120, 41, 31, 24)
 Opportunistic Diseases:
 CD4+ <400→ Oral Thrush; Tinea Pedis, Recurrent VZV, Reactivated TB, ↑ bacterial infections
 <200→ React HSV, cryptosporidiosis, Isospora, Disseminated coccidoidomycosis, Pneimocystis pneumonia
 <100→ Esophageal candidiasis, Toxcoplasmosis, Histoplasmosis
 <50→ CMV retinitis/esophagitis, Disseminated MAI complex, Crytococcal Meningitis
 Assoc Neoplasms
 Kaposi's Sarcoma → HHV-8
 invasive cervical Carcinoma→ HPV
 CNS Lymphoma and Non-Hodgkins Lymphoma
Togaviridae
+ssRNA, enveloped through budding. Replication similar to poliovirus
Alphaviruses
 An ARBOVIRUS (Arthropod Borne)
 Clinical Manifestations:
 Intro into blood via insect bite→ multiply in RE system→ VIREMIA (Chills,F,V,Pain): STAGE 1 SYMPTOMS
 Stage 2→ alphavirus enters CNS through BBB resulting in encephalitis
 Causes lesions on entire brain, neurophagia, and encephalomalacia→ neck muscle rigidity, confusion, convulsions
 Mortality→ EEE>WEE>VEE
 Virus Examples: (Names for location of first isolation)
 Eastern Equine Encephalitis (EEE):
 Severe illness w/ 50-70% mortality→ least prevalent of the equine encephalitis viruses in the US
 Highest incidence in areas of heavy spring rains and high mosquito populations
 Western EE: 2-3% mortality
 Venezuelan EE: Primarily in horses→ 0.5% mortality when infecting humans
 Age→ WEE fx children infection:clinical cases (50:1); Adults (1000:1)

 For EEE- most fatalities are seen in elderly→ >30%
 Dx→ serology and or isolation from brain tissue on autopsy
 Tx→ Supportive and Vaccines (Formalin inactivated or attenuated strains)
Rubivirus- Rubella
(German Measles)
 Togaviridae→rubivirus→rubellavirus (NOT AN ARBOVIRUS like other toga's)
 +ssRNA/Icos capsid and ENV w/ glycoprotein spikes
 Like most RNA viruses→ req's RNA polymerase from viral genome
 Replicate in cytoplasm** (Poliovirus is +ssRNA model)
 Infectious process→ mod infectious
 Primary→ URTI and Regional LN's from droplet spread→ INC is 2-3wks→ viremia after URTI to skin, placenta, joints kidney
 Mac-Pap rash lasting 1-3 days w/ ↑ LN's, esp behind ears
 Outcome in children and adults→ run course→ resolve w/ rash
 Or inapparent infxn w/o rash
 Possible sequelae from infection→ arthritis in females/congenital infection in pregnant women
 Exanthem→ immunological basis for rash (mac/pap)→ face to trunk to extremities
 Factors for Dx→ location of rash/Progression of rash/ time of year (spring)/ geographic locale
 Infection→ Non-imm preg women→ viremia→ fetal infection→ death (1st mon of preg) or CRS (3rdmonth)
 Congenital Rubella Syndrome (CRS)→ not a lytic infection of cells but does prevent normal growth and cause chrom dmg
 HIGHLY Teratogenic→ Brain (MRation), Heart/vessel, eye(cataracts), ear (deaf), HSmegaly
 CRS→ viral excretion for up to 2yrs (nasal secretions and urine)→ RARE guillain barre
 Dx→ antiviral IgM in cord or infant blood (4x increase Ab titer in child or adult- before day 7 and after 17)
 Vaccination→ RA-27-3 and Cendehill→ produce imm and little/no cong dfx in pregnancy vaccination
 LIVE ATTENUATED→ vaccinate all women and children
 TRIVALENT→ MMR unless allergy to neomycin or prev injection→ MMRV also available
Astroviridae
 Mamastroviruses and Avastroviruses→ high levels of gastroenteritis in children and adults
 +ssRNA, nonseg, no envelop→ STAR on EM
 Infxn→
 Fecal-oral and person to person→ anti-astrovirus Ab's in young children (most w/ no sxs- some N/V/F/D/Abdo pain)
 Dehydration is rare
 Dx→ ELISA, EM, PCR Techniques→ Imm is life-long
Negative Sense RNA

Bunyaviridae
 -ssRNA, helical capsid and enveloped, 3 segments
 Rift Valley fever and CE← 10 serogroups
 May cause hemorrhagic fever
California Serogroup
 California encephalitis virus→ frequently found in Mississippi and Ohio River Valleys (Mosquito Vector)→Peak- late summer
 LaCrosse Encephalitis→ member of california serogroup seen in Nicholas County, WV
 Clinical Dz:
 Mild course to abrupt onset→ bifrontal headache, fever, vomiting→ occasional aseptic meningitis
 Systemic and meningeal signs abate w/n a week
 15% of children develop sequelae
Orthobunyavirus
Bunyamwera Serogroup
 Hemorrhagic fever viruses→ febrile illness (crimean-congo hemorrhagic fever)
 Transmitted by ticks
Phlebovirus:
 Transmit via sand flies
 F/ M/ photophobia, neck/back stiffness and papules over the body→ total recovery and immunity for ~2yrs
Hanta Virus:
 Korean Homorrhagic fever virus:
 urine and excrement of rodents and causes a hemorrhagic fever → may lead to renal syndrome
 Hantavirus Pulmonary Syndrome
 American SW→ aerosols from mouse feces→ HPS
 ↑ w/ more rainfall in SW (better rodent habitat)
 5% of HPS confirmed east of Mississippe River (two in Randolph County, WV)
 Ribavirin has some effectivity in early HPS infection
Deltavirus (Unclassed)
Filoviridae
 Formerly considered a Rhabdovirus
 Long tubular structure→ -ssRNA, helical nucleocapsid surrounded by envelope
 MARBURG and EBOLAVIRUSES→ NOT ARBOVIRUSES
Marburg virus and Ebolavirus:

 African hemorrhagic fever→ involves liver and can lead to encephalitis
 Isolated from monkeys and their cells→ can infect humans
 High Fever, HA, myalgia, diarrhea→ conjunctivitis, rash and abdominal pain
 hemorrhages in the skin, nose, GI and GU lead to shock→ 53-88% mortality
 Transmission:
 Natural route unknown→ bats expected
 Ebola a potential agent of bioterrorism→ Russians researched them and attempted to weaponize
Orthomyxoviridae
 -ssRNA, 8 segments forInfluenza A,B; 6 segments for Influenza C
 Helical nucleocapsid of RNA, NP, PB1, PB2, PA
 7 structural proteins→ H, N, PB1, PB2, PA, M, NP and one NS

 PB1, PB2 and Pa→ subunits of RNA polymerase
 envelope studded w/ 2 glycoproteins→ H and N
 N→ imp in budding and ↓ visc of mucus in vivo during infections
 W+ viruses→ poor TC growth, use embryonated egg, allantoic cavity
 Drift→ Same DNA just point mutated→ epidemic
 Shift→ Species differe- "Strange" segment DNA→ pandemic
 Antigenic sin→ each new infxn of Influenza A→ body responds w/ strongest Ab vs 1st subtype to infect person
Influenza- A, B, C
 Droplet spread via aerosols→ infx resp epith (N ↓ mucus visc)→ syst sxs not req viremia
 IgA is most important defense, but short lived
 Tx:
 Amantadine/Rimantadine→ blocks uncoating (for egg allergies/imm-supp'd)- now Type A resistances
 Ribavirin→ inh viral RNA synthesis (guanidine)
 Zanamivir and Oseltamivir→ Neuraminidase inhibitor (for those who can't receive vaccines)
 Antigens→ NP and M Ag's; H ag's
 H and N are strain specific
 Replication:
 Nuclear and cytoplasmic phases
 -ssRNA→+RNA(mRNA) shortened by 20-30 nt's → mRNA has 3' poly A tail added and a donated short 5' cap
 Capped = translation/transcription copy
 each mRNA=1protein
 Each -ssRNA copied to complete +ssRNA for replicative purposes through Rep intermed formation
 Nucleocapid (8-seg's) budds to acquire env (H+ and N+)→ H must be cleaved to become infectious
 Influenza B
 Shift and Drift less frequent→Children ↑ freq/sxs than adults
 Guillain-Barre→ paralysis from demyelination
 Vaccines:
 TIV- inactivated virus→ creates IgG Ab's
 Split Vaccine- Purified glycoprotein vaccine (H and N)
 Intranasal→ LAIV→ IgA + IgG
Paramyxoviridae
 -ssRNA, nonsegmented, helical nucleocapsid, Env w/ 1 or 2 glycoprot spikes
 Produce RNA-dep-RNA polymerase
 6 structural proteins: NC, L, P, M, F, and H or HN(H)→ L+P= large polymerase
 Glycoprotein spikes:
 gpHN- H and N properties with 1 gp; gpH- H properties, no N; gpF- Fusion glycoprotein
 H→ attachment to receptor; F→ fusion of viral env and outer cell membrane( must be prot cleaved for activity- form giant cells)
 replication:
 Cytoplasmic site→ measles may have nuc stage
 Influenza is model of replication (req virion polymerase)
 Newcastle Disease Virus→ hemorrhagic conjunctivitis (chicken host that farmers aquire- zoonosis)
Morbilliviruses (H,F)
Measles virus
Rubeola (Measles)
 Mac-pap rash (morbiliform)
 Spread by resp droplets (HIGHLY CONTAGIOUS)
 Clinical
 Koplik spots → buccal mucosa before rash
 Atypical in adults: fever and vesicular rash (salt grains surrounded by red halo)
 "Cough, coryza, conjunctivitis"
 Complications (↑ imm-supp) : Pnuemonia, Otitis media, Myocarditis , LATE/rare→ Subacute sclerosing panencephalitis
 Treatment
 Supportive therapy
 Vit A ↓ complications
 MMR Vaccine!!!!!!!!!
Paramyxovirus (HN, F)
 Mumps, Parainfluenza virus
Parainfluenza
 Type 1: Croup**, ARD, newborn pneumonitis, adult colds, coryza, pharyngitis, bronchitis, children, bronchiolitis
 Type 2: croup (laryngotracheobronchitis)
 Type 3 and 4: ARD, bronchitis, pneumonia
 Infxn in young children→ 3>>1,2>4
 IgA for immunity and viremia not nec for Dz
Pneumovirus (F)
 RSV and metapneumovirus
 One antigenic type→ Posses gpF- mediates syncytia formation
 Causes bronchiolitis and pneumonia in infants (#1 cause) and most sever under 8 months
 Maternal IgG does not protect→ may ↑ severity (Immune complex Dz component)
 IgA most important→ re-infection may occur but 2º infections are milder
 Tx:
 RSV-Ig and anti-RSV monoclonal Ab→ IV Px for high risk (palivizumab to high risk babies)
 Killed RSV vaccine may be harmful, Ribavirin aerosol questionable
 RSV>parainfluenza 3>> 1,2>4
 Dx w/ Rt-PCR
 Human metapneumovirus→ related to RSV and usually infx those under 5
Rhabdoviridae
 Vesiculovirus, Vesicular Stomatitis Virus (VSV) and Lyssavirus (rabies)
Lyssavirus- Rabies Virus

 -ssRNA; NONsegmented; Helical nuceocapsid, BULLET-SHAPED capsid→ invariably fatal after protract incubation period***
 Produced RNA-dep-RNA polymerase (L + NS proteins)
 Envelope:
 5 Proteins→Large (L); Matrix (M); Major Nucleocapsid (N); Nucleocapsid Small (NS); Env Glycoprotein (G)
 Env glycoprotein (G)→ Produces neutralizing Ab, acts as hemagglutinin, inhibits cell processes
 Replication:
 Virus attaches to receptors on cell surface→ rec vary w/ cell type
 AChR - nicotinic Acetylcholine receptor; Neural cell adhesion molecule (NCAM)
 Enters Cell via phagocytic engulfment→ replicates as does influenza virus but only in cytoplasm (-ssRNA prototype)
 Two events must occur to viral genomic RNA: mRNA's and new -ssRNA from RI's
 Viral progeny bud from plasma membrane to form bullet shaped virus→ G glycoprotein extending from its envelope on its outer surface
 3 Phases of Disease:
 1- Incubation Phase: Prolonged wk/mos
 2- Prodromal Phase: F/M/HA/Sore throat/ V/ N→ VIRAL TRANSPORT - retrograde axoplasmic- rep in dorsal ganglia and travels up SC
 3- Neurological Phase: Infxn of brain→ descends into eyes, glands, visceral organs
 Excitement stage→ Apprehension, fear, hydrophobia (biting stage in dog), aerophobia
 Manic Stage→ Convulsions and death
 Transmission:
 Bats a reservoir- replication occurs but w/o disease (virus in saliva)
 Skunks in US (foxes,raccons)- Major source in US→ Dogs minor in US- but #1 in most of the world
 Virus enters host thru bite (Found in saliva, CNS, Urine, Lymph, Milk, blood)- Hunters skinning/dressing animal at risk
 Inc→ 10d-2yrs (most 2-3mos)→ correspond to time to multiply in muscle or CT at point of entry and move up nerves
 In CNS→ Dest of Cortex, midbrain, pons, medulla, posterior horn of SC ( REMEMBER- POLIO is ANTERIOR HORN)
 Dx→ Negri Bodies (cytoplasmic inclusions in brainstem cells); RT-PCR and DIF
 Rabies specific Ab→ appears late and not useful for Dx
 Treatment:
 Vaccine→ Long inc period allows time to immunize!!!!

 Semple→ rabiesvirus infected nervous tissue and inactivated with phenol (7-14 daily injections)
 Envokes allergic encephalomyelitis complications
 Human diploid vaccine→ 5 doses (0,3,7,14,28 days)→ expensive, Px-ive, and ↑ ab for 2yrs
 Deliver via IM injection→ fat will ↓ fx (so no gluts)→ Deltoid in adults or thigh/delt in kids
 Other→ RVA, chick embryo vaccine, recomb vaccinia vaccine (for raccoons)
 Steps to treat→ Flush wound, Inject 1/2 humans rabies globulin and start vaccine on day 0 (diff sites),
Ambi-Sense RNA Viruses

Arenaviridae
 -ssRNA in a multisegment circle, helical nucleocapsid, env of dense lipid bilayer, Ribosome-like structures in core
 Replicate in cytoplasm and use viral RNA polymerase
 Rodent Reservoirs
 Two Serogroups: Old World Complex and New World Complex
 Old World Viruses→ Lymphocytic Choriomeningitis Virus (LCM) and Lassa Virus
 New World viruses→ Tacaribe virus complex (junin and machupo viruses)
Lymphocytic Choriomeningitis Virus (OW)

 human infection at 5% frequency (higher in close-contacts of virus)
 OUtbreaks in humans who purchased hamsters or from house mice (urine and feces)
 Clinical Dz→ flu-like illness or aseptic meningitis (rare)
 Fatal dz reported from organ transplant with LCMV infected donor
 Pregnant women→ 1st/2nd trimester→ vertically transmitted to fetus (severe disease)
Lassa Fever Virus (OW)

 Febrile illness in humans w/ 20% mortality→ multi-organ (rarely benign)
 Clinical→ skin hemorrhages, high fever, mouth ulcers and severe muscle ache
 Spread to humans from humans OR rodents (rats in africa→ chronically infected)
Tacaribe Complex (NW)

 Hemorrhagic fevers in South America, trinidad, FL everglades, Argentina (Junin) and Bolivia (Machupo)
 Primary source→ rodent urine and feces; Mosquitos possible minor vector
 Clinical→ Hem fever w/ petechiae, bleeding into the GI tracts, uterus, nasal cavity and GU tract
 15- new world arenaviruses recognized
 Possible bioterrorism agent
Double-Stranded RNA Viruses

Reoviridae
 12 segment dsRNA, external icosohedral capsid + core capsid w/ NO envelope (Acid stable)
 Tubular structures link core (containing RNA polymerase and capping enzymes) w/ external capsid
 Replication:
 Replication and Transcription occur WITHIN THE CORE CAPSID
 Virus infects target cells via cell surface receptor→ entry and outer capsid is removed
 GENOME REMAINS IN INNER CORE→ core assoc enzymes activate and RNA synth ensues (genomic and mRNA)
 tubular projects serve as transport channels for the viral mRNA's into the cytoplasm
 Once mRNA's are in cytoplasm→ new capsid proteins are synthesized
 viral genome segments are encapsidated and progeny produced
Orthoreovirus
 Vertebrates serve as host (no invert multiplication)
 3 types (diff by Neutr and hemagglutination inhibition)
 All have been found in healthy children→ Ab is very prevalent→ exact resulting illness unclear
 Isolated during minor febrile illness, diarrhea/enteritis of children
Orbovirus (arbovirus)
 ALL replicate in insects- some in vertebrates
 SERIOUS ANIMAL PATHOGEN→ Blue-tongue virus of sheep; African Horse Sickness virus
Coltivirus (Arbovirus)
 Colorado Tick Fever→ mild febrile Dz w/o a rash**
 myalgia, chills, ocular pain, severe muscle/joint pain, N, V, diphasic fever→ complete recovery
 Vector is dermacentor andersoni
Rotavirus
 2 primaru human serotypes→ 11 segment ds RNA (will not grow in TCx)
 Causes→ infantile diarrhea (endemic)→ ubiquitous, fecal-oral route, HIGHLY INFXUS
 Isolated from 40-50% nonbacterial gastroenteritis in young patients hosp'd in winter (33% of diarrhea hosp in children)
 Infxn Course:
 infects intestinal cells at tips villi in Small intestines→ cells lyse→ poor absorption of sugar, salts, and water
 Diarrhea after 2-4 day incubation→ BRIGHT GREEN WATERY STOOLS
 Sxs:
 diarrhea, F, Abdo pain, vomiting, dehydration→ fatal unless treated with AGGRESSIVE REHYDRATION THERAPY**
 Dx→ Rotozyme ELISA, Virus in stool via EM, and PCR methods for viral RNA
 Vaccines:
 Rotashield→ possible link to intussusceptions
 Rotarix: Oral, Live-attenuated vaccine with ONE strain
 RotaTeq: Oral, Live attenuated pentavalent Vaccine (5 diff Ag forms via molec bio→ genome resortment)
 3 doses→ 2,4,6 months
Viroid-like Agents
Hepatitis D Virus
 36nm particle w/ circular, covalently closed ssRNA and delta Ag (HD Ag) PLUS a donated HBsAg
 DEFECTIVE hepatitis virus→ requires HBV as helper virus in replication
 HBV and HDV→ enhanced severity of Dz
 Dx→ HDAg in Bx tissue, High Titer of total antibody vs HDAg, persistent IgM specific
Prions and Slow Viruses

Subacute Sclerosing Panencephalitis Virus
 Caused by measles virus→ helical nucleocapsid found in brain Bx (1 case SSPE / Million measles infxns)
 Prog demyelination/Dgenerative neuro Dz→ Fatal!
 MASSIVE ↑ in hypertrophic astrocytes and proliferation of microglial cells
 Co-Cultivation→ Bx'd cells in permissive cells→ measles like formations
JC Virus (PML)
 Progressive Multifocal Leukoencephalopathy→ Caused by Papovaviruses (linked to JC virus and SV-40- both oncogenic)
 Assoc/w lymphoproliferative disorders→ prog neuro disorder and rare
 JC virus Ab's is common but if infection in imm-supp'd→ paralysis, mental deterioration→ death w/n 1 year
Animal Lentiviruses
Prions (PrP)
Scrapie:
 Dz of sheep→ tremors, ataxia- NO demyelination, NO pleocytosis, NO fever, NO meningeal signs→ sheeps scrape off wool
 Causes spongiform changes in gray matter→ may have genetic and infectiour origins
 Agent termed PrPSC → not virus→ aberrant protein closely related to normal cell protein
 forms Scrapie Assoc, Fibrils→ brain, spleen→ may form rods sim to amyloid
 Normal form is protease sensitive and anchored to phosphatidylinositol glycan of cell membrane; aberrant form is resistant
 Human encephalopathies→ genetic/Infectious→ genetic- chrom 20q and 2/ infectious d/t being transmissible (but atypical)
 CJD→ 144bp insert @ codon 53 plus other mutations in PrP gene
 PrPSC - w/s heat to 80C; formalin/UV/Rad resistant; Transmissible by animals
 Inactivated by chlorox
 Accumulates in cells and depot'd in cytoplasmic vesicles→ can be released from cell surface
 Causes normal PrP to fold abnormally
Kuru
 Spongiform encephalitis among Fore people of N. Guinea→ Trans when eating parts of dearly departed
Creutzfeld-Jakob Dz:
 Presenile dementia; Ataxia, myoclonic fasciculations, semiconsiousness, involuntary muscle group contractions
 Agent unknown but pathology similar to Kuru→ SAF in infectious tissues
 Transmit via corneal transplants and contaminated brain electrodes
Other Spongiform encephalopathies:

 Fatal familial Insomnia
 Sporatic Fatal Insomnia
 Possible→ Alper's, Pick's, Alzheimer's
 Mad-Cow Dz
Recap on Hepatitis viruses:

For more information see individual entries:
Acute Hepatitis Histologic changes→ ballooning degeneration, Hepatocyte necrosis, portal inflammation.
Vowels hit your bowels (A and E)→ No Envelope dependancy so they are not destroyed in gut→ fecal-oral tranmisson.
Hepatitis A Virus
 Picornovirus→ found in Poop (friend of polio and cocksackie) → ENTEROVIRUS 72
 30day inc
 Hep A→ AAA→ Acute, Alone (no carrier state), asymptomatic
 Dx on EM, ↑ anti-HAV IgM
 Tx→ pooled ƴ-globulin w/n 1-2 wks of exposure
Hepatitis B Virus
 HepaDNAvirus→ transmit parenteral sexual, maternal placental
 2-3MONTH incubation→ Carriers
 HBeAg→ ↑ INFECTIOUSNESS!!!
 Contained reverse transciptase: DNA genome from RNA intermediate
 Hep B→ Blood Borne→ adw-asxs, ayw→ dialysis and drug addicts
 Dx→ ELISA, Ground Glass cytoplasm, HBx protein binds p53 protein→ ↑ cancer risk
 Tx→ HBIG pooled (neonates), Peg-a-IFN, Nucleoside analogs (lamivudine, adefovir, entecavir)
Hepatitis C Virus
 Flavivirus→ Citrus is flavorful (HCV)→ Carriers, Chronic, Carcinoma, and cirrhosis
 #1 for post-transfusion OR IVD Use hepatitis
 Dx→ EIA; NAT, Imm-blot test
 Tx→ Peg-IFNa ± Ribavirin→ G2/G3>G1 in Tx response
 Polymerase and Protease (teleprevir and boceprevir) inhibitors
Hepatitis D Virus
 Defective and Dependant Hepatitis virus→ Needa HepaDnavirus (HBV)→ Reqires HBsAg for its envelope
 May Coinfect or superinfect those with HBV (↓↓↓ prognosis)
Hepatitis E Virus
 RNA hepevirus→ Enteric, Expectant, Epidemics
 20% mortality if infection in PREGNANT women
Mycology- more than yeast infections ?
Anti-Fungal Agents:
Amphotericin B Deoxycholate
 GOLD STD of antifungal therapy
 MoA: Binds sterols of fungal plasma membrane (Ergosterol)→ alters membrane permeability→ Leaks essential cell contents (K+, etc)
 May be cidal or static depending on concentration
 Kinetics→ POOR CSF penetration (Intathecal Admin req'd)
 ADRs: (Amphoterrible)
 Nephrotoxic: in 80%→ direct vasoconstrictive effect on afferent renal arterioles→ ↓ Glom and renal tubular blood flow
 Cause K+/Mg+ and bicarb wasting and ↓'d EPO production (usually reverisble)→ oft req ↓ om dose or admin change
 Hematologic: Normochromic; normocytic anemia→ direct inhibition of erythrocyte or EPO production
 returns to normal 2-3 months after d/c Tx
 Electrolyte Imbalance→ K and Mg loss
 Infusion related ADRs: Shaking/Chills/Fever/Myalgia/Arthralgia→ Premedicate
 Coverage: Few exceptions to coverage
 Aspergillosis/Histoplasmosis/Blastomycosis/Coccidioidomycosis/Paracoccidioidomycosis/Cryptococcus/Candida
Lipid formulations
 Amphotericin B Lipid Complex/ Amphotericin B Colliodal Dispension/ Liposomal Amphotericin B
 ↓ incidence of Nephrotoxicitiy but w/ equal efficacy→ however dosing amt is much higher than parent compound
5-Flucytosine
 MoA: deaminated to 5 fluorouracil BY FUNGUS SPECIFIC enzyme- cytosine deaminase
 Acts as antimetabolite competing w/ uracil (inh pyrimidine metab and ultimately RNA and protein synthesis)
 Kinetics: Penetrates CSF 60-100%
 ADRs: Bone Marrow Hypoplasia (Anemia, Lekipenia)→ ↑ with long term Tx or combo w/ Ampho B
 Use: Serious infections of candida or cryptococcus; SYNGERY with Ampho B (Cryptococcal Meningitis)
-Azoles
 MoA: interfere w/ FUNGAL CYP450-dependant enzymes resp for demethylation of Ianosterol and conversion to ergosterol
 TRIAZOLES→ ↑ affinity of fungal P-450 vs mammalian
 May be static or cidal
 ADRs:
 uncommon Hepatitis (80% arise in first 3 months of this does occur)→ Anorexia,M,N/V;↑LFTs and Jaundice
 CHF is a contraindication (may contribute to CHF through ↑ing dysfunction)
 Drug-Drugs:
 Antacids/PPIs/H2 blockers→ ↓ absorption d/t ↓ acidity
 Cyclosporin→ ↑'s concentrations
 Warfarin→ ↑ effects
Ketoconazole
 Absorption: Rapidly abs from GI→ but has pH dep-bioavailability→ ↑pH = ↓abs
 Coverage:
 Blastomycosis; Candidiasis; Tinea; Vulvovaginal Candidiasis
 Pulmonary OR Disseminated→ Histoplasmosis and Coccidiodomycosis
 Special ADR: DOSE dependant depression of testosterone and ACTH (inh cortisol synthesis)
 gynecomastia, impotence, decreased libido, azospermia; menstrual irregularities
Fluconazole
 Kinetics:
 Absorption: Rapidy from GI (F>90% for oral OR IV)→ pH has no effect

 Dist: Wide dist and readily enters CSF (50-94% of serum lvl)
 Elim: Renal excretion (60-80% excreted unchanged)
 Coverage:
 Cryptococcal Meningitis; Coccidoidomycosis (pulm/diss)
 Px and Tx of candidiasis (oropharyngeal, esophageal, systemic)→ Torulopsis and Krusel sp RESISTANT
Itraconazole
 Distribution: Wide but poor into CSF
 Coverage:
 Aspergillosis/Blastomycosis (pulm/Extrapulm); Cryptococcal Meningitis; Coccidoidomycosis (pulm/diss)
 Histoplasmosis and tinea unguium (onychomycosis
 Place in therapy→ oral Tx for histo/blasto w/ fewer ADRs than AmphoB
 Use AB if severe/life-threatening→ then change to Itra w/ improv
Voriconazole
 DO NOT USE DURING PREGNANCY
 Kinetics:
 Abs: ↓ w/ high fat meal by34% (F=94% normally)
 Dist: 42-67% CSF concentration
 Elim: Metab by liver (2C9/3A4)
 ADR: VISUAL DISTURBANCES***; rash and ↑LFTs
 Indications:
 Invasive aspergillosis/ infections of Scedosporium apoispermum and Fusarium spp
 May provide a significant advantage over ampho B in Tx of aspergillosis
Posaconazole (triazole)
 Structure Similar to itraconazole
 Tx for Candida and Aspergillosis in severely imm-comp'd/ or oral candidiasis in healthy
 Few ADRs→ HA/ GI disturbances; may ↑LFTs
 Inhibits 3A4
 Contraindications→ concomitant use w/ ergot alkaloids, pimozide, quinidine
Caspofungin Acetate
 MoA: Echinocandin (blocks cell wall synthesis) AND Glucan synthesis inhibitor (B-1,3-D-Glucan)- NOT FOUND IN ANIMAL CELLS
 Indicatons:
 Candidiasis (equ results as ampho B)
 C. Parapsilosis (higher MICs)
 Invasive Aspergillosis
 No activity vs Cryptococcus
 ADRs:
 Phlebitis/HA/F
 ↑ LFTs; SrCr→ Monitor
Griseofulvin
 MoA: Distrupts microtubules/mitotic spindle formation→ arrest cell div in metaphase
 Indications:
 Dermatophytosis (Tinea spp) → *When topical if ineffective
Terbinafine
 MoA: Inhibits squalene epoxidase (key enzyme in sterol biosynthesis in fungi)
 ADRs:
 Hypersens/Rash→ Erythema Multiforme→ TOXIC EPIDERMAL NECROLYSIS
 Liver enzyme abnormalities
 HA
 Drug-Drugs:
 Cimetidine→ ↓'s Terbinafine's clearance by 33%
 Rifampin→ ↑'s Terb clearance by 100%
 Cyclosporin→ Terb ↑'s clearance of cyclosporin
 Warfarin→ uncommon interaction
 Coverage:
 Indications: Onychomycosis (Cosmetic problem→ risk may be greater than benefit)
 At least as effective as itraconazole (and is less expensive and fewer interactions BUT more ADRs)
Oral Thrush and Topicals:

Nystatin
 Thrush: Swish and swallow- NO GI ABSORPTION
Clotrimazole
 Thrush: Keep in mouth until dissolved
Ampho B suspension
Topicals:
 Creams/Solutions: Inflamed/Fissured intertriginous areas
 Powders: Confined to mild lesions or Px in tinea pedis
 Sprays: NOT ON FACE
 TX→ Tinea Pedis -4wks; Others only 2
Systemic Mycoses:
 Mild Dz:
 pt ambulatory and tol's oral Tx
 Itra>Ket>Flu (Amph B may be useful in mild aspergillosis)
 Flu for cryptococcal meningitis
 Mod Dz:
 Significant but not immediately life-threatening Dz- patient may tolerate oral Tx
 Itra>Ket>Flu; Amph B for Candida and Aspergillosis
 Flu for cryptococcal meningitis
 Sev Dz:
 Worst case scenario of host and site of infection
 AMPHO B→ add 5-FC to Tx for Cryptococcal meningitis
Systemic Mycoses
Histoplasmosis
 Histoplasma var and Duboisii→ Dimorphic ( mold @ 25C, Yeast at 37C)
 Capsulatum→ Broad regions of Ohio and Mississippi River Valler, Mexico and Central South America
 Duboisii→ Tropical areas of africa
 High in soils high in nitrogen (contaminated w/ bird or bat droppings)
 outbreaks often assoc/w exp to bird roosts, caves, and decaying buildings or urban renewal projects
 Dz:
 Acute pulmonary Dz w/ mild flu-like sxs (Coin lesion on x-ray)
 Chronic Progressive 2º lung Dz→ located in apices
 Extra-pulmonary→ Adrenals and Liver→ may fully Disseminate
 Dx→ Tuberculate Macroconidia, LIVE INTRACELLULARLY w/n alveolar MQ's;
 visualize on Giemsa periph blood stain (GMS or PAS)→ usually found in monocytes or PMN's
 Serology→ Ag Detected in blood and urine
 Tx→ Amphotericin B, Itraconazole for mild cases
Blastomycosis
 Blastomyces Dermatitidis→ Dimorphic ( mold @ 25C, Yeast at 37C)
 East of the Missisipi River, Great lakes, and SE US, Some central America
 Soil, rotting word, Feces of birds and bats
 Dz:
 Sxs in less than 50%→ May form granulomatous nodules
 Acute pulmonary (lobar segmental consolidation- mimics bacterial pneuomnia)
 Chronic Pulmonary Lobar infiltrates (mimics bronchogenic Carcinoma)
 Extrapulmonary Dissemination (skin and bones)
 Hematogenous Spread (Prostate, liver, spleen, kidney, CNS)
 Dx→ KOH prep on sputum, pus, skin lesions
 BROAD BASED BUDDING YEAST
 Tx→ Amphotericin B, Itraconazole, Voriconazole
Coccidiomycosis
 Coccidioides Immitis→ Dimorphic ( mold (Arthroconidia) @ 25C, Yeast spherules** at 37C)
 Pasada's Dz, San Joaquin valley fever, VALLEY FEVER and desert rheumatism→ SW US AND CALIFORNIA
 Favors→ arid, alkaline soils and hot summers → outbreaks in duststorms and earthquakes
 Primarily a pulmonary Dz→ 60% of the infections in endemic areas = asxs (Symptoms will resemble TB)
 Dx→ Sputum/Pus/Gastric Washings/CSF/Bx→ ENDOSPORULATING SPORULES
 Tx→ Amphotericin B then maintenance w/ fluconazole or itraconazole
Paracoccidiomycoses
 Paracoccidoides Brasilenses→ South American Blastomycosis→ Dimorphic ( mold @ 25C, Yeast at 37C)
 Middle of Mexico and central/South America→ MOST FROM BRAZIL
 Dz:
 Granulomatous Dz of mucus membranes (white plaques on buccal mucosa), skin and lungs
 Invades membranes of mouth→ teeth fall out
 Dx→ PILOT'S WHEEL arrangement @ 37C (Can use methenamine Silver Stain)
 Tx→ Amphotericin B and TMP/SMX→ Itraconazole provides best recovery
Opportunistic Mycoses:
Candida Albicans
Aspergillus Fumigatus
 MONOMORPHIC→ Septate hyphae that branch at acute angles
 Fumigatus, flavus, Niger, Terreus
 Inhale spores→ Allergy, Sinusitis, Aspergilloma, Pulm Aspergillosis, Disseminated Aspergillosis
 Dz:
 Allergic Aspergillosis→ asthma from mold spore (Mucus plug in lungs but no tissue invasion) HIGH IgE Ab titer
 Aspergilloma (fungus Ball)
 Invasive Aspergillosis→ in severe neutropenia→ FUO
 Disseminating Aspergillosis→ Most frequently to the brain
 Tx→ Amphotericin B (Surgical Removal of Aspergilloma)
Cryptococcus Neoformans
 Pigeon/Chicken droppings → MONOMORPHIC
 Acidic Mucopolysaccharide Capsule, Phenol Oxidase Positive (BLOCK EPINEPHRINE)
 Dz:
 Subacute/Chronic
 HIGH fatal meningoencephalitis→ vision problems and headache→ delerium, nuchal rigidity→ coma/death
 Also infect lung and skin→ form granulomatous rxn w/ giant cells
 Dx: INDIA INK
 Micro Exam of CSF→ Encapsulated budding yeast→ PHENOLOXIDASE POSITIVE
 Culture→ mucoid colonies that are round and urease positive
 Tx→ Amphotericin B and 5-fluorocytosine (5-FC)
Mucor and Rhizopus (sp)

 Mucormycosis→ Mold w/ irregular nonseptate hyphae branching at WIDE ANGLES
 Dz mostly in Ketoacidotic Diabetic and Leukemic Patients
 Fungi proliferate in walls of blood vessels and cause infarction and necrosis of distal tissue
 Rhinocerebral, frontal lobe abscesses
Pneucystis Jiroveci
 Round cup shaped organism→ Lacks Ergosterol (Ribotyping and DNA homology)
 Obligate parasite of human→ Resp tract = portal of entry (↑ rate in AIDS pts→pneumonia)
 Dz:
 Foamy Exidate seen w/n alveolar spaces (w/ intense interstitial infiltrate composed of mainly plasma cells)
 May see diffuse alveolar damage, noncaseating granulomas, inflamm, infarct-like coag necrosis
 Dx→ Bx of BA Lavage fluids; Ground Glass Radiographs; Gomori's Methenamine Silver-Stain (Rounded cup organism)
 Tx→ TMP-SMX
Sporotrichis Schenkii
 Sporotrichosis
 Nodular lesions of cut/subcut and ajd lymphatics→ suppurate, ulcerate and drain
 5-types
 Lymphocutaneous, fixed cutaneous, mucocutaneous, disseminated and pulmonary
 Entry/dose and immune response→ determine infection type
 Lymphocutaneous Sporotrichosis
 Sporothrix schenkii- dimorphic @ 35º (mold→yeast)
 Common in US→skin and lymph fx
 Clinical
 nodular and ulcerative along lymph that drain 1º site
 Local w/o fever, malaise and regional LN involve
 Fixed cutaneous lesions
 Limited to skin and d/n involve lymphs (also include primary, secondary pulmonary sporotrichosis and disseminated Dz)
 Dx- Culture, Skin tissue in 10%KOH→ CIGAR shaped budding yeast

 Asteroid bodies→ rays of eosinophilic material radiating from central (basophilic)yeast like cell/s (rep host Imm resp)
 Eosinophilic material is a complex of fungal Ag material and host Ab protein
 Tx- KI for cutaneous ifxn or Ampho B for disseminated
Superficial Fungal Infections

Pityriasis Versicolor
 Asxs colonization of stratum corneum→ malassezia furfur (pityrosporum orbiculare)
 Lipophilic yeast-like org (rich in sebaceous areas)
 Risk factors: ↓ rate of desquamation, poort nutrition, XS sweating, pregnancy
 Hyper/Hypo-pigment macular lesions that scale→ upper torso/arms/abdomen
 Diagnostic procedures:
 KOH prep of Bx'd skin→ SPAGHETTI and MEATBALLS
 Wood's lamp: yellow/yellow-green
 Cx→ rarely done
 Tx: Topical Preparations w/ disulfide, hyposulfite, thiosulfate, salicylic acid or 1% ketoconazole
Tinea Nigra:
 Exophiala Werneckii→ dimorphic melanin producing fungus
 Gray to black, well demarcated macular lesions→ palms #1
 DX'd: KOH prep showing stubby dark hyphae (RULE OUT melanoma and Nevi)
 2% salicylic acid or tincture of iodine
Superficial Hair Infections:

Black Piedra:
 Piedraia hortae
 Firm hard black concretion developing along hair shaft
 Dx: KOH prep show dark brown hyphae tightly adherent to hair shaft
 Cut hair or shampoo with preparations containing sodium hyposulfite
White Piedra:
 Trichosporon beigelii→ dimorphic fungi w/ arthroconidia and blastospores
 Soft pale nodules on hair shaft (scalp, bear, mustache, pubes)
 KOH preps→ transparent sheath along hair shaft
 Cut hair or shampoo w/ selenium sulfide
Cutaneous Mycoses
 Dermatophytes→ skin hair nails→ keratin as N-source
 Ringworm or tinea (classed by either Sporulation pattern-microsporum,trichophyton,epidermophyton- or location of lesion)
 Pathos: Dermatophytes are keratinophilic
 Microsporum: Skin and hair keratin [fusiform/spindle shaped conidia]
 Epidermophyton: skin and nail keratin [Snow shoe or beaver's tail macroconidia with thin smooth walls]
 Trichophyton: Keratin of hair/skin/nail [pencil/cigar shaped microcodia that are >in number than macrocondia]
 Immunity:
 No classical humoral or cell mediated protective immunity
 Allergic reactioin→lesion @ different sites (dermatophytids ir ids)
 Dx: KOH, Cx on special media, Wood's lamp
 Treatment:
 local: topical miconazole, clotrimazole, econazole
 Azoles: interfere w/ cyp450 dep enzymes in sterol synth→ ↑ membrane perm and in sterol synth
 Systemic:
 Griseofulvin→ inh microtubular system of fungi
Dermatophytes of hair:
 Tinea capitis (scalp hair, eyebrows, eyelashes; HIGHLY CONTAGIOUS)
 Most freq microsporum and trichophyton (T. tonsurans in US)
 Dx: KOH prep, wood's light (greenn)
 Tx: Griseofulvan
 Tinea Barbae
 T. Mentagrophytes
Dermatophytes of skin:
 Tinea Corporis (smooth skin)
 Microsporum and trichophyton: T. Rubrum, T. Mentographytes, M. Canis
 SXS- roundish lesion with vesiculated and inflamed margins, int is dry and scaly
 Dx: KOH prep, Cx
 Tx: Topic→ miconazole and clotrimazole; Oral→griseofulvin
 Tinea Cruis (groin/jock-itch)
 T. Rubrum- US
 Athletes food (Tinea pedis and manum)
 T- Rubrum, T. mentagrophytes, E. Floccosum
 Intertriginous peeling, pruritis, fissuring→ sxs vary by agent
 Dx- KOH and culture
 Tx- Griseofulvin
Dermatophytes of Nails
 T. Rubrum or T. Mentagrophytes
 Sxs: Paronychial inflamm→ grooved nail, brown/black color
 Distingish from candidal onychomycosis by accum of subnail plate detritus and darker color absent in candida
 Dx→ dep on agent
 Tx- Griseofulvin→ 3-4mos
Subcutaneous Mycoses
 Common features
 Trauma @ infxn site before lesion develops
 Occurs in trauma prone sites
 Agents found in soil or on decaying vegetations
 ALL PRODUCE GRANULOMAs
Chloroblastomycosis
 Dermatacious fungi (pigmented)- phialophora and cladosporium (#1 is Fonsecaea pedrosi)
 tropic/subtropical
 Seen in workers injured in woods
 papules at inoc site→years→ verrucous crusts→vegetate into cauliflower like appearance
 Dx- Pigmented fungi in tissue sections (sclerotic/medlar bodies→ penny bodies/coins)
 Tx- Surgical excision if early/ 5-flucytosine (oral)
Phaeohyphomycosis (Subcut fungal infection)

 Greek "dark"
 Heterogenous group of darkly-pigmented fungal elements
 Cerebral and Subcut infesions→ chronic nasal sinusitis, prosthetic valve endocarditis, keratomycosis and widely dissem infxn
 Etiology: Dermatacious hyphomycetes→ produce melanin in cell wall (subcut→ dark walls hyphae)
 Dx- PAS stain or methenamine silver: dark staining hyphae
 Tx- Resection of localized lesion; ampho B/ oral ketoconazole and itraconazole
Parasitology- Quick and dirty

Mostly info from first aid- some lecture notes
AntiParasitic Agents
Anti-Malarials
Chloroquine
 MoA: May combine w/ DNA, Inh DNA-polymerase OR inh heme polymerase (protects parasite from ferri IX from Hb degrad)
 High FX vs asexual and erythrocytic forms
 Kinetics: 4dy halflife (1/wk Px)
 Resistance via efflux
 ADRs:
 HA/N/V; Blurred vision, dizziness, fatigue, confusion
 Rare: depigmentation of hair, corneal opacities, heme disorders, psoriasis exacerbation, dose-dep retinopathy
 Contraindicated in psoriasis and retinal Dz
 Indications: Px and Tx of Malaria; (Inflam amebiasis & Inflam Dz's→ not FDA approved)
Primaquine
 MoA: interfere w/ mitochondrial function
 Only agent available for TX of exoerythrocytic hyponozoite forms of vivax and ovale in liver
 NOT FOR PX
 ADRs:
 HEMOLYSIS if G6PD-deficient→ abdo cramps, nausea, mild anemia
 Rare: Hematologic abnormalities
 Radical Cure: P. Vivax/P. Ovale (Px of relapse)
 Use after chloroquine Tx/Px and esp if exp to Ovale/Vivax
Quinine
 MoA: Poss sim to Chloroquine
 Many resistant strains
 DoC for parenteral therapy vs Falciparum
 ADRs:
 Low Therapeutic:Toxic index
 Cinchonism: dose-rel and reversible→ Hypersens/hypoglyc/hemolysis in G6PD-deficients
Quinidine
 Similar to quinine
 ADRs: EKG changes, Hypotension
Mefloquine
 Quinine derivative→ Px of P. Falciparum
 Schizontocidal DrugL no FX on exoerythrocytic stage
 Resistance to mefloquine is increasing in thailand and W. Africa
 ADR→ HALLUCINATIONs/VIVID DREAMS
Pyrimethamine
 Combo of sulfonamide and quinine→ Tx of chloroquine resistant plasmodia
 MoA: Rel to TMP→ reversibly bind dihydrofolate reductase
 ADRs:
 N/V/D/Anorexia;
 Hypersens/Hematologic rxns→ Anemia d/t folate ↓ (give leucovorin replacement)
Prophylaxis and Treatment

 Px: P. Vivax; Ovale; Falciparum; Malariae→ Chloroquine OR Mefloquine/Doxycycline if chloroquine-R
 Tx: P. Vivax; Ovale; Falciparum; Malariae→ Chloroquine OR Quinine Sulfate/Doxycycline OR pyrimethamine if chloroquine-R
Anti-Giardials
Metronidazole
 #1 Giardia Tx
 also tinidazole and nitazoxanide
 MoA: Nitro group is electron acceptor forming a reduced cytotoxic agent→ toxic form binds protein and DNA and gen free radicals
 Also useful for anaerobic bacteria; entamoeba histolytica, E. Polecki, giardia lamblia, trichomonas vaginalis
 Alt for blastocystic hominis and balantidium coli
 Systemic activity→ for severe dz or liver abscesses
 ADRs: GI fx; metallic tatse, disulfiram-like effect (alcohol intolerance via aldehyde dehydrogenase inhibition)
Furazoladine
 Good for kids (suspension)→ GI complaints, mild hemolysis in G6PD-def
Amebicidic Agents
Iodoquinol
 Luminal Agent→ asymptomatic amebiasis
 ADRs: Seizures, encephalopathy→ HIGH iodine content can interfere with TFT's
Paromomycin
 Alt to iodoquinol
 ADRs: Potentially nephrotoxic, ototoxic (IV)
Metronidazole
See above
Other Anti-Protzoals
Leshmaniasis
 use antimonials→ Sodium stibogluconate and Meglumine antimoniate
 Ampho B and pentamidine are alternatives
Trypanosomiasis
 S. American (Chagas)→ Nifurtimox
 African Sleeping sickness (TseTse)→ Eflornithine, suramin if abroad→ ***PENTAMIDINE in US****
Toxoplasmosis
 Pyrimethamine (+leucovorin) w/ sulfdiazine
 Alternate Tx: pyrimethamine (+leucovorin) w/ clindamycin
Anti-Helminthics
Mebendazole
 MoA: Binds helminthic tubulin and blocks microtubule assembly→ also inhibits glucose uptake (immob and death)
 ADRs: abdo pain (ADRs rare at normal dosage)
Ivermectin
 MoA: GABA receptor agonist→ paralysis of organism
 DoC for strongyloides; ADRs→ minimal (GI/Drowsiness)
Pyrantel Pamoate
 MoA: Depolarizing NM blocking agent
 Ascariasis, hookworm, pinworm
 ADRs: minimal (GI/HA/Drowsiness)
Thiabendazole
 MoA: Inhibits fumurate reductase of susceptible helminths and may inh microtubule assembly
 Second line for strongyloides
Anti-Trematodes
 Schistosomiasis
Praziquantel
 MoA:↑ Ca2+ perm
 Also DoC in Cestodes/some nematodes
Anti-Cestodes
 Tapeworms
 Niclosamide (↓ ATP prod in mitochondria)
Quick Tx overview:
Bug: Primary Tx: Alternative
Enterobius (pinworms): Pyrantel pamoate OR Mebendazole OR
**Albendazole**
Ascariasis (roundworms): Albendazole** OR Mebendazole Or pyrantel
pamoate
Filiariasis: Diethylcarbamazine
Trichuriasis: Mebendazole Albendazole (alt)
Hookworm: Aldbendazole OR Pyrantel Pamoate OR
Mebendazole
Strongyloides (threadworm): Ivermectin Thiabendazole (alt)
The Parasites
Protozoa (GI):
Giardia Lamblia
 Foul, Fatty, Frothy, Floats (hiker/camper), Diarrhea
 Reactive Arthritis, Lactose Intolerance, or Mal-Abs may follow( Fat, Vit A, B12, D-Xylose)
 Cysts in watter- Beavers, St. Petersburg Russia
 Dx→ Trophozoites or cysts in stool, Fecal Ag ELISA; DNA Probes; 6 flagella and 2 "eyes"
 Tx→ Metronidazole #1→ Peromomycin if pregnant
Entamoeba Histolytica
 Bloody diarrhea/constipation, Liver Abscess, RUQ pain, Necrotizing Colitis
 Histology→ FLASK-SHAPED ulcers is submuc abscess ruptures; Cysts w/ 4 nuclei
 Transmission→ Cysts in water, MSM
 Dx→ Serology ± trophozoites or cysts in stool; RBC's in cytoplasm of Amoeba; charcot-Leyden Xtals in stool, Stool Ag or PCR
 Tx→ Metronidazole and Iodoquinol
Cryptosporidium
 Acid Fast Cysts
 Severe diarrhea in AIDS pts→ Mild Dz in healthy host
 Cysts in Water
 Dx→ Cysts on acid fast stain; ELISA; IFA
 Px/Tx→ Filter city water supplies, (maybe Nitazoxanide- ALINIA)
Protozoa (CNS)
Toxoplasma Gondii
 "evil cyclops" cell
 Brain abscess in HIV→ RING-ENHACING lesion
 Congenital Toxoplasmosis→ "Classic Triad"→ Chorioretinitis, hydrocephalus, intracranial Calcifications
 Cysts in meat or cat feces→ CROSSES PLACENTA
 Dx→ Serology/Bx
 Tx→ Sulfadiazine + Pyrimethamine
Naegleria Fowleria
 Rapidly fatal meningoencephalitis
 Swimming in freshwater lakes → enters via cribiform plate
 Dx→ Amoebas in spinal fluid→ NO Tx available
Trypanosoma Gambiense/Trypanosoma Rhodesiense

 African sleeping sickness→ Enlarged lymph nodes, recurring fever, Somnolence, coma
 Gamb→ Winterbottom's Sign, West/Central Africa
 Rhod→ RAPIDLY fatal, East African Game parks
 Transmit→ TseTse Fly→ painful bite→ chancre
 Dx→ Blood smear, Mott Cells in CSF- eosinophilic plasma cells, Xenodiagnosis
 Tx→ Suramin is blood borne, Melarsoprol if in CNS
Protozoa (Visceral)
Trypanosoma Cruzi
 Chaga's Disease of mostly S. America→ dilated cardiomyopathy, megacolon, megaesophagus
 Reduviid bug (Kissing bug)→ painless bite (Brazilian Athlete)
 Dx→ blood Smear Tx→ Nifurtimox
Leishmania Donovani
 Sperm-like protozoa→ visceral Leismaniasis (Kal-Azar) w/ sandfly vector
 Spiking fevers, HSmegaly, pancytopenia
 Dx→ MQ's containing amastigotes (forms that lack flagella)
 Tx→ Sodium Stibogluconate
Protozoa (Hematologic)
Malaria:
 Cyclic Fever, HA, Anemia, Splenomegaly
 Dx→ anyone traveled to malaria prone area w/ flu-like illnes (prophylactic therapy or not)→ Thick(infxn) and Thin(spcs) blood smears
Plasmodium Vivax/Ovale
 Ovale- W. Africa→ Anopheles Mosquito→ Vivax and Ovale have dormant phase- HYPNOZOITES
 Serology available for P. Vivax
 Kill hypnozoites w/ primaquine (don't use if G6PD Deficient)
 Protective Traits- Sickle Cell trait, Ovalocytosis, Duffy Negative Blood type for P. Vivax only
Plasmodium Falciparum
 Severe Dz; Daily cycles; parasitized RBC's occlude capillaries of brean, kidney and lung
 Anopheles mosquito bites→ Sporozoites invade liver cells→ form schizonts→ daughter merozoites→ rupture from liver cells
 → enter RBC's forming Ring Trophozoites and mature into Schizonts→ Schizont rupture causes Malaria symptoms
 Minor routes→ blood transfusion, IV, Mother-fetus
 Sxs→ 1-3 wks after transmission; flu-like illness, hypoglycemia, Lactic acidosis, Anemia,
 RBC's form knobs that adhere to capillary endothelium→ clog vessel→ infarct (MS changes, Seizures, Coma, Death)
 Children- Rapid→ cerebral malaria, Acidosis, hypoglycemia, anemia
 Px/Tx:
 DEET; Netting
 Chloroquine Px→ Central Am- Panama canal to US, Haiti, Dominican Republic and some Middle east
 Px Malarone → NOT IN PREGNANT WOMEN
 Px Mefloquine→ Safe in pregnancy but NOT in heard conduction problems- vivid/disturbing dreams
 Px Doxycycline→ not in children <8yo, pregnant or lactating→ ADR-photosensitivity
 Px Primaquine→ Px or destroying hypozoites- do not use w/ G6PD deficiency
 Tx ***Chloroquine***→ Only where not resistant→ Mefloquine #2
 Tx Malarone
 Tx→ Artemesinin based combo Tx→ if PO- must be combined w/ something else
 Protective traits→ Sickle Cell, Ovalocytosis, G6PD Deficiency(Avoid primaquine and Fava Beans)
Plasmodium Malariae
 Dz may not present for 50-70 years
 Protective traits→ Sickle Cell trait and ovalocytosis
Babesia
 Ixodes Tick (deer tick that feeds on rodents)→ Babesiosis- f ever and hemolytic anemia (NE US- Martha's Vineyard, Long Island, Wisconsin)
 Hemolytic anemia can be fatal if spleenless
 Dx→ thick and thin smears (RBC w/ no pigment and appears as maltese cross or ring form)
 Tx→ Quinine and Clindamycin (Px- remove ticks promptly)
Protozoa (STD's)
Trichomonas Vaginalis
 Vaginal Itching w/ foul, purulent, green discharge; men may have urethritis/epididymitis or show no sxs
 Wet mount→ Motile trophozoites on wet mount with twirling motion→ Tx w/ metronidazole
Nematodes:
N- Necator (US hookworms)
E- Enterobius (Pinworms)
M- Mosquito Borne (Wuchereria and Brugia
A2- Ascaris and Ancylostoma
T3- Trichurisis, Trichiniella, Toxocara
O- Onchocerca (River Blindness)
D- Dracunculus (Guinea Worm- walk in water wells- almost eradicated)
E- Eye worm (Loa Loa)
S- Strongyloides (Threadworm)
Transmit→ Eat eggs/larvae; Direct invasion of skin; Insect bite

Can treat most with one of the "-bendazoles"- Worms are "Bendy"
 Cutaneous Larva Migrans (slow serpiginous tracks)
Enterobius Vermicularis (Pinworms)  Tx→ -bendazoles or pyrantel palmoate or Ivermectin
 Food contam/w eggs→ intestinal infection→ anal pruritis
(SCOTCH TAPE TEST) Dracunculus Medinensis
 Egg may contain Dientameoba fragilis  In drinking water/walk in wells→ skin inflamm and
 tx→ -bendazole or Pyrantel Pamoate ulceration→ Remove w/ pencil pulling SLOWLY from leg
 Tx→ Niridazole
Ascaris Lumbricoides (Roundworm)
 Eggs visible in feces/ intestinal infection→ may obstruct or Onchocerca Volvulus
may pass "a fish worm"  Transmit by female black flies near waterfalls/rivers
 Loffler's→ pulm infection, cough, fever, eosinophilia  Hyperpigmented skin and river blindness (black skin and
 Tx→ -bendazoles or pyrantel pamoate black sight)→ Allergic rxn possible to microfilaria)
 Tx→ Ivermectin for rIVER blindness
Trichinella Spiralis (Whipworm)
 undercooked meat (pork/bear)→ inflames muscle (usually Loa Loa
calf)→ periorbital edema  Transmitted by deer fly, horse fly and mango fly→ swelling
 Rectal Prolapse, Barrel shaped egg w/ plugs in skin- see worm crawling in conjunctiva
 Tx→ -bendazoles  Tx→ Diethylcarbamazine
Strongyloides Stercoralis (Threadworm) Wuchereria Bancrofty

 Larvae from soil penetrate skin of feet, intestinal infxn→ V,  Female Mosquito→ blocks lymph flow (elephantiasis in
D, Anemia 9mos to 1yr)
 Loffler's Syndrome; Larva Currens/Racing Larva→ rapid rash  tx→ Diethylcarbamazine
 Dx→ String test or Larvae on O&Px3
 Overhwhelming infection→ Pt on steroids→ 70% Toxocara Canis
eosinophils→ Crashes  Food contaminated with eggs→ granulomas and visceral
 Tx→ -bendazoles or Ivermectin larva migrans
 Granuloma in retina MAY BE MISTAKEN for a retinoblastoma
Ancylostoma Duodenale/Necator Americanus  Dx→ ELISA, high eosinophils
(Hookworms)  Tx→ Diethylcarbamazine
 Larvae penetrate skin of feet→ inest infection may cause
anemia (sucks blood from intest wall)
Cestodes (Tapeworms)
Taenia Solium (Pork Tapeworm)
 Ingestion of larvae incysted in undercooked pork→ intestinal tapeworms
 Ingestion of eggs→ Cysticercosis/Neurocysticercosis(mass lesions/swiss cheese image of brain)
 Example→ migrant worker w/ new onset seizures
 Tx→ Praziquantel (but -bendazoles for neurocysticercosis)
Taenia Saginata (Beef Tapeworm)

 Beef Tapeworm→ Tx with Praziquantel
Diphyllobothrium Latum (Fish Tapeworm)

 Cold freshwater (Alaska/Michigan)→ vitamin B12 deficiency→ megaloblastic anemia
 Tx→ Praziquantel
Dypylidium Caninum
 Dog Tapeworm→ via fleas→ Itchy anus and cucumber seeds on a string
Echinococcus Granulosus
 Eggs in dog feces→ cysts in liver if ingested→ may cause anaphylaxis if antigens released from cyst (neutralize w/ EtOH injection)
 Tx→ -bendazoles
Trematodes (Flukes)
Schistosoma
 Snail fever→ Peurto rico, Great Lakes, Cape Cod/New england
 Swimmer's itch (freshwater avian); Clamdigger's Itch (saltwater Avian)
 Cause liver damage and katayama fever (typhoid like illness)
 Eggs w/ a handle
 Tx→ Praziquantel
Clonorchis Sinensis
 Undercooked fish→ inflammation of biliary tract→ pigmented gallstones (ass/w cholagniosarcoma)
 tx→ Praziquantel
Paragonimus Westermani
 Undercooked crab meat→ inflammation and 2º bacterial infection of the lung→ hemoptysis
 Praziquantel

Systems Overview
Nervous System Infections:

Encephalitis CSF Profile in Meningitis:
Viral Bacteria: ↑↑ Protein, ↓↓ Glucose, PMN's, ↑ Pressure
Viral: ↑/Nml Protein, Nml Glucose, Lymphocytes, nml Press
HSV-1
Fungal: ↑ Protein, ↓ Glucose, Lymphocytes, ↑Pressure
HSV-2
Rabies Virus
Japanese Encephalitis (and other Arboviruses)
Protozoan Axon/Synapse Pathogenesis
Toxoplasma Gondii
Clostridium Tetani
Trypanosoma Brucei Gambiense
Clostridium Botulinum
Trypanosoma Brucei Rhodesiense
Mycobacterium Leprae
Poliovirus
Meningitis
Neonatal
Streptococci Agalactiae (Group B Strep)
Listeria Monocytogenes
Escherichia Coli
6mos-6yrs
Haemophilus Influenza Type B
6yrs-60yrs
Poliovirus
Aseptic
Coxsackie virus
Echovirus
Mumps Virus
Poliovirus
Fungal
Cryptococcus Neoformans

Cardiovascular System Infections:

Septic Shock Endocarditis
E. Coli Native Valve
K. Pneumoniae
Strep Viridans
Enterobacter
S. Bovis
P. Mirabilis
S. Pyogenes
P. Aeruginosa
E. Faecalis
B. Fragilis
S. Aureus
S. Areus
S. Epidermidis
S. Pyogenes
S. Agalactiae (Neonatal- Group B strep) IV Drug Users
Rheumatic Heart Disease (Tricuspid #1)
B act erial :
S. Pyogenes
S. Aureus
Myocarditis Streptococci
Viral E. Faecalis
Fung al :
Coxsackie Type B
C. Albicans
Protozoan Prosthetic Valve
Trypanosoma Cruzi
A cut e:
Bacterial S. Epidermidis
S. Aureus & E. Faecalis* (comp of endocarditis) S. Aureus
C. Diphtheria Gram-Neg Bacilli
B. Burgdorferi C. Albicans
Sub acut e:
Streptococci

Gastrointestinal System Infections:
Dental Caries Small Intestines

S. Mutans Non-inflammatory / Watery Diarrhea
Hepatitis B act erial
V. Cholera
Hepatitis A-E Viruses
Enterotoxigenic E. coli
Yellow Fever Virus
C. Perfringens
Other Liver Infections B. Cereus
E. Histolytica- Liver Abscesses S. Aureus
L. Donovani- Visceral Leishmaniasis Vi ral
E. Granulosus- Hydatid Cysts Rotavirus
Schistosoma Sps.- Liver Flukes Norwalk Virus
Biliary Tract infection Adenovirus
Prot ozoan
E. Faecalis
G. Lamblia
Ulcers C. Parvum
Helicobacter Pylori
Large Intestine/Distal Small
Food Poisoning( Common Causes) Inflammatory/Bloody Diarrhea
L ess t han 6hr i ncub at i on: B act erial
S. Aureus- Toxin Ingested- V/N/D Shigella Species
B. Cereus- Toxin Ingested- V/N (reheated rice) S. Typhi (May go systemic)
Great er t han 10hr i ncub at i on: S. Enteritidis
B. Cereus- Toxin Ingested- D/cramps C. Jejuni
C. Perfringens- Bacteria Ingested -D/Cramps Enterohemorrhagic E. Coli
EnteroInvasive E. Coli
Y. Enterocolitica (May go systemic)
V. Parahaemolyticus
C. Difficile
Prot ozoan
E. Histolytica

Respiratory Infections:
Pharyngitis/Laryngitis Community Aquired Pneumonia

B act erial B act erial
S. Pyogenes M. Pneumoniae
M. Catarrhalis S. Pneumoniae
N. Gonorrhoeae H. Influenzae type B
C. Diphtheriae C. Pneumoniae
Vi ral L. Pneumophila
Common Cold Viruses M. Catarrhalis
Adenoviruses S. Aureus
RSV Nocardia
M. Tuberculosis
Epiglottitis C. Psittaci
Vi ral
H. Influenza Type B
Influenza Virus
RSV
Croup Fung al
B act erial C. Immitis
M. Pneumoniae H. Capsulatum
Vi ral B. Dermatitidis
Parainfluenza Virus
Influenza Virus
Atypical Pneumonia
RSV
M. Pneumoniae
L. Pneumophila
Otitis Externa C. Pneumoniae
P. Aeruginosa C. Burnetti
Various Viruses
Otitis Media
S. Pneumoniae HIV-Associated Pneumonia
H. Influenza Type B P. Carinii
M. Catarrhalis M. Tuberculosis
S. Agalactiae- (Neonatal- Group B Strep)
Sinusitis
S. Pneumoniae
H. Influenza type B
M. Catarrhalis
S. Aureus
Rhinitis
Rhino Virus
Coronavirus
Influenza C virus
Coxsackieviruses- A and B types
Parainfluenza Viruses

Urinary Tract Infections:

Uncomplicated UTI's Sexually Transmitted Urethritis
E. Coli N. Gonorrhoeae
S. Saprophyticus C. Trachomatis
Complicated UTI's Glomerulonephritis

Cather, Calculi and obstruction S. Pyogenes
E. Coli
E. Faecalis
P. Aeruginosa
K. Pneumoniae
P. Mirabilis
Genital tract Infections:

Male: Female:
Epididymitis Pelvic Inflammatory Disease
N. Gonorrhoeae N. Gonorrhoeae
C. Trachomatis C. Trachomatis
Orchitis Urethritis
Mumps Virus C. Trachomatis
N. Gonorrhoeae
Urethritis HSV
N. Gonorrhoeae
C. Trachomatis Vulvovaginitis
U. Urealyticum C. Albicans
T. Vaginalis T. Vaginalis
HSV-2
Proctitis Both:
C. Trachomatis Proctocolitis/Enterocolitis
N. Gonorrhoeae C. Jejuni
HSV-1,2 S. Flexneri
T. Pallidum E. Histolytica
Enteritis
G. Lamblia
C. Parvum
Sexually Transmitted Diseases:

Ulcerative Lesions
HSV-1,2→ Painful vesicles Pathogens with systemic effects
T. Pallidum→ Nonpainful indurations HIV, HTLV, HBV, CMV, T. Pallidum
H. Durcreyi→ Painful Chancroid
C. Trachomatis→ No pain, solitary, indurated Common Vaginal Infections
C. Albicans→ Itchy/White/Small amt/Clumped
Warty Lesions T. Vaginalis→ Itchy/Yellow/Copious Amt
HPV and Molluscum Contagiosum Gardnerella Vaginalis→ White-Grey/ Mod amt/ Malodorous

Pelvic inflammatory Dz
 Spectrum of inflamm of fem upper genital tract→ endometritis/Salpingitis/oophoritis/tuboovarian abscess/pelvix peritonitis
 Sxs→ dull continuous uni/bil lower abdomenal/pelvic pain→ fever/V/Vag discharge/Irreg vag bleeding
 Tenderness on latermotion of cervix and adnexal fullness (sxs may be mild)
 N. Gon/C. Trach most case> bacteroides/peptostreptococcus/G. Vaginalis/streptococcus/mycoplasmas
 Polymicrobe infxn common- DX→ multifactorial
 Dx
 Cervical motion tenderness/ uterine or adnexal tender w/ lower abdo or pelvic pain
 Addition criteria→ oral temp>101F/ cerv/vag mucopur discharge w/ ↑ WBCs/ ↑ ESR and CRP
 Do not delay Tx→ Infert from tubal occlusion/ Ectopic Preg/ Chronic pelvic pain
 Tx→ Cefotetan OR Cefoxitin PLUS Doxycycline in Hosp/ Ceftriaxone plus Doxycycline ± metronidazole
STI syndromes and symptoms

Derm
 Warts→ HPV
 Rash/Alopecia→ T. Pallidum
 Arthritis/Dermatitis→ N. Gonorrhea/C. Trachomatis
 Scabies/Pubic Lice
Pharyngitis
 N. Gonorrheae/ Herpes Simplex
Genito-Urinary
 Discharge/Dysuria (N.Gonorrhoea, C. Tachomatis, Trichomonas Vaginalis)
 Discharge/Prostatitis ( N. Gonorrhoae, C. trachomatis, T. Pallidum)
 Genital Ulcer/Lymphadenopathy ( Herpes Simplex, T. Pallidum, H Ducreyi, K Granulomatis, LGV)
 PID or Scrotal Pain (epididymitis)→ (N. Gonorrhoae, C. Trachomatis)
Viral STI's
 Four of top ten are viral→ HPV, HSV-2, HIV, HBV
 HPV→ human papilloma virus→ Circ dsDNA→ NonEnv w/ icosahdral capsid
 HSV-2→ Linear dsDNA→ ENV and Icos capsule
 HIV→ Retrovrisu→ linear ssRNA (diploid)→ ENV and COMPLEX Capsid
 HBV→ dsDNA partial circ→ ENV and Icos capsid
 TO a lesser extent→ HAV (Picornovirus),HCV (Flavivirus),HDV (Deltavirus), Molluscum Contagiosum, CMV and HHV-8, HTLC-1

Skin/Muscle/Bone Infections:
Vesicles Necrotizing Fasciitis
VZV, HSV-1,2 S. Pyogenes
Smallpox Virus C. Perfringens
Coxsackievirus A
Molluscum Contagiosum Virus Myositis
C. Perfringens
Bullae S. Aureus
S. Aureus T. Spiralis
S. Pyogenes T. Solium
C. Perfringens Coxsackievirus B
Dengue Fever Virus
Erysipelas
S. Pyogenes Osteomyelitis
S. Aureus
Cellulitis S. Typhi - **Danger in Sickle Cell Patients
P. Multocida- cat/dog bites
S. Pyogenes
S. Aureus
P. Aeruginosa Septic Arthritis
P. Multocida N. Gonorrhoeae
S. Aureus
H. Influenzae
Major Causes of Rash:

Viral
VZV Chickenpox Widespread vesicles with red base appearing as "dew on a rose petal"- Centrifugal
spread
HSV-1,2 Herpes Vesicular lesions in mouth/eye or genital/perianal region
Coxsackie A Herpangina, Hand-foot- Red oropharynx vesicles, vesicles on hand/foot/mouth
and mouth Dz
Smallpox Virus Smallpox Macules form first in the head then later in Extremeties, become pus filled then
spread
Molluscum Contagiosum Molluscum Contagiosum Small pink tumors with central dimple on trunk and anogenital regions
Rubella Virus Rubella Mac-pap rash→ begin on face and spread to extremeties
Measles Virus Measles Starts on head and progresses to feet- disappears in same order
HHV Roseola In infants→ rash on trunk
Parvovirus B19 Erythema Infectiosum "Slapped Cheek"
Bacterial
S. Pyogenes Scarlet Fever "Sandpaper Rash" Trunk & spread outward
R. Rickettsii Rocky Mt. Spotted Fever Mac-Pap rash on palms/soles then spread prox to trunk→ centripetal
R. Prowazekii Epidemic Typhus On trunk and spread outward→ centrifugal- spares palms/soles/face
B. Burgdorferi Lyme Disease Erythema chronicum migrans→ annular red lesion surrounding clear bite mark
T. Pallidum 2º Siphilis Mac-Pap Rash on palms and soles

Other infections with Cutaneous Symptoms

Bacterial
B. Anthracis Anthrax Ulcerous lesion with blackened necrotic eschar
F. Tularensis Tularemia Papule→ ulcer with black base
Y. Pestis Bubonic Plague Cutaneous hemorrhagic necrosis with black color
M. Leprae Leprosy Anesthitized Lesions vulnerable to secondary damage
A. Israelii Sinus Tracts Sinus tracts form through skin, muscle, bone and organs
Viral
HPV Warts
Fungal
S. Schenkii Sporotrichosis Ulcerating Nodules
Ringworm (tinea) infections Dermatophytoses Inflammation, itching, scaly skin and
pustules
Protozoan
Leishmania Species Cutaneous Leishmaniasis Skin or mucosal ulcers
Infection types:
 Impetigo: superficial skin
 Folliculitis→Furuncle→Carbuncles: progressive spread from follicle to subcut tissue (carbuncle→fever/chills/syst fx)
 Spreading Infxn:
 Impetigo: epidermis ==Strep Pyogenes ±S. Aureus==
 Erysipelas: dermal lymphatics (exthema→erysipelas→cellulitis) ==Strep Pyogenes==
 Cellulitis: Subcut fat layer (minor injury to severe septicemia in 24-48hrs)
 Can be caused by H. Flu type B in non-vaccinated
 P. Multocida in dog/cat bites
 Necrotizing infxn: Tissue destr/ vessel thrombosis, poor infil of inflamm cells, spread along fascial planes
 Nectrotizing fasciitis (50% have myonecrosis if d/t GAS)
 Type I: polymicrobe→ aerobes and anaerobes (common after surgical procedure)
 Type II: Monomicrobe→ Group A Strep (MRSA is minor)
 Myonecrosis- necrotizing muscle infxn (ass/w local trauma)
 Clostridium (perfringens, septicum, histolyticum, sordellii)
 Gas always found in skin/ fascia/deep muscle spared
 Non-clostridial→mix of gas-prod anaer/aerobes (Diabetes ass→ foul odor)
 Abscess formation: Folliculitis/furuncle/carbuncle ===S. Aureus==
 Necrotizing infxn: fasciitis ==anaerobe±microaerophile== and gas gangrene(myonecrosis) ===C. Perfringens===
 Macule: flat/nonpalp
 Papule: palpable
 Vesicle: palp/fluid filled lesion (bulla; serous fluid w/ small # inflam cells)
 Pustule: palp/pus filled lesion (mostly PMN's w/ serous fluid)
Systemic infxns w/ skin sxs:

 Salmonella (typhi/paratyphi): "Rose Spots" that contain bacteria
 P. Aeruginosa: Ecthyma gangrenosum
 Strep pyogenes: scarlet fever (toxin induced erythematous rash)
 Staph Aureus: TSS (toxin induced rash and desquamation)

The Bug Parade Clinical Microbiology

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The Bug Parade Clinical Microbiology

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Clinical Microbiology

The Bug Parade

Carboxy Penicillins .................................. 17

Clofazamine ................................................ 25 Bacilli........................................................... 34

Yersinia Pestis ......................................... 43 Mycoplasma Pneumoniae ....................... 52

Lamivudine.............................................. 58 Inclusion Bodies: ..................................... 61

Noroviruses (Norwalk Virus) ................... 73 Pneumovirus (F) ...................................... 81

Picornoviridae ............................................. 74 Lassa Fever Virus (OW) ........................... 83

Enteroviruses (acid stable) ...................... 75 Tacaribe Complex (NW) .......................... 83

Hepatitis A Virus ..................................... 75 Double-Stranded RNA Viruses ..................................................

Coxsackieviruses ..................................... 75 Reoviridae ................................................... 83

ECHOViruses: .......................................... 75 Orthoreovirus ......................................... 83

Poliovirus ................................................ 75 Orbovirus (arbovirus) .............................. 83

Rhinoviruses............................................ 76 Coltivirus (Arbovirus) .............................. 84

Retroviridae ................................................ 76 Rotavirus ................................................. 84

HIV (and LAV)→ ...................................... 76 Viroid-like Agents ....................................................................

Togaviridae ................................................. 77 Hepatitis D Virus ......................................... 84

Alphaviruses............................................ 77 Prions and Slow Viruses ...........................................................

Rubivirus- Rubella ................................... 78 Subacute Sclerosing Panencephalitis Virus . 84

Astroviridae ................................................ 78 JC Virus (PML) ............................................ 84

California Serogroup ............................... 79 Scrapie: ................................................... 84

Orthobunyavirus ..................................... 79 Kuru ........................................................ 85

Deltavirus (Unclassed) ................................ 79 Creutzfeld-Jakob Dz: ............................... 85

Filoviridae ................................................... 79 Other Spongiform encephalopathies: ..... 85

Marburg virus and Ebolavirus: ................ 79 Recap on Hepatitis viruses: ......................................................

Orthomyxoviridae ....................................... 79 Hepatitis A Virus ..................................... 86

Influenza- A, B, C ..................................... 80 Hepatitis B Virus ...................................... 86

Paramyxoviridae ......................................... 80 Hepatitis C Virus ...................................... 86

Morbilliviruses (H,F) ................................ 80 Hepatitis D Virus ..................................... 86

Paramyxovirus (HN, F)............................. 81 Hepatitis E Virus ...................................... 86

Mycology- more than yeast infections ?............................................................................................

Nystatin................................................... 89 AntiParasitic Agents .................................................................

Clotrimazole ............................................ 89 Anti-Malarials.............................................. 94

Ampho B suspension............................... 89 Chloroquine ............................................ 94

Topicals: .................................................. 89 Primaquine.............................................. 94

Systemic Mycoses: ...................................... 89 Quinine ................................................... 94

Blastomycosis ......................................... 90 Pyrimethamine ....................................... 94

Coccidiomycosis ...................................... 90 Prophylaxis and Treatment ..................... 95

Paracoccidiomycoses .............................. 90 Anti-Giardials .............................................. 95

Opportunistic Mycoses: .............................. 91 Metronidazole......................................... 95

Candida Albicans ..................................... 91 Furazoladine ........................................... 95

Aspergillus Fumigatus ............................. 91 Amebicidic Agents ...................................... 95

Cryptococcus Neoformans ...................... 91 Iodoquinol ............................................... 95

Mucor and Rhizopus (sp) ........................ 91 Paromomycin .......................................... 95

Pneucystis Jiroveci .................................. 91 Metronidazole......................................... 95

Sporotrichis Schenkii ............................... 91 Other Anti-Protzoals ................................... 95

Leshmaniasis ........................................... 95 Trichomonas Vaginalis ............................ 98

Anti-Trematodes ......................................... 96 Dracunculus Medinensis ......................... 99

Praziquantel ............................................ 96 Onchocerca Volvulus............................... 99

Anti-Cestodes .............................................. 96 Loa Loa .................................................... 99

Quick Tx overview: ...................................... 96 Wuchereria Bancrofty ............................. 99

Giardia Lamblia ....................................... 97 Taenia Solium (Pork Tapeworm) ............. 99

Entamoeba Histolytica ............................ 97 Taenia Saginata (Beef Tapeworm) ........ 100

Cryptosporidium ..................................... 97 Diphyllobothrium Latum (Fish Tapeworm)

Protozoa (Visceral) ...................................... 97 Clonorchis Sinensis................................ 100

Trypanosoma Cruzi ................................. 97 Paragonimus Westermani ..................... 100

Leishmania Donovani .............................. 98 Systems Overview....................................................................

Protozoa (Hematologic) .............................. 98 Nervous System Infections: ...................... 101

Malaria: ................................................... 98 Cardiovascular System Infections: ............ 102

Plasmodium Vivax/Ovale ........................ 98 Gastrointestinal System Infections: .......... 103

Plasmodium Falciparum .......................... 98 Respiratory Infections: .............................. 104

Plasmodium Malariae ............................. 98 Urinary Tract Infections: ........................... 105

Babesia.................................................... 98 Genital tract Infections: ............................ 105

Protozoa (STD's) .......................................... 98 Male: ..................................................... 105