Antimicrobial Review

Daryl Norwood, PharmD Associate Professor FAMU COPPS

Objectives
Identify different types of bacteria
Determine appropriate antibiotic for empiric treatment Identify different antibiotics and their respective classes Understand the pharmacology and spectrum of
different antibiotics

Determine antibiotics of choice for certain infections

Bacteria
Gram-positive: stain dark blue
or violet

Gram-negative: stain red or

pink

Cocci: spherical shaped

Bacilli (rods): rod shaped Spirillum: spiral shaped

Gram positive cocci and gram negative bacilli

Gram-positive Aerobes
Gram-positive cocci Streptococci: (pneumonococcus, enterococcus,
viridans) Staphylococci: (S. aureus, S. epidermidis)

Gram-positive rods (bacilli)

Corynebacterium Listeria

Gram-negative Aerobes
Gram-negative cocci
Neisseria: (N. meningitidis, N. gonorrhea) M. catarrhalis

Gram-negative rods
Enterobacteriaceae (E. Coli, Klebsiella, Enterobacter,
Citrobacter, Proteus, Serratia, Salmonella, Shigella) Pseudomonas Haemophilus influenzae (coccobacilli morphology) Campylobacter

Anaerobes
Gram-positive cocci
Peptococcus and peptostreptococcus

Gram-positive rods (bacilli)

Clostridia (C. perfringens, C. tetani) Propionibacterium acnes

Gram-negative rods (bacilli)

Bacteriodes (B. fragilis, B. melaninogenicus) Fusobacterium

Atypical Bacteria
Atypical Bacteria
Chlamydia (C.trachomatis, C. psittaci, C.
pneumoniae (TWAR), LGV, Ureaplasma Mycoplasma pneumoniae Legionella pneumophilia Mycobacteria (Myobacterium tuberculosis, M. avium intracellulare/complex)

Other Notable Bugs

Fungi (Candida sp., Aspergillus, Histoplasma, Cryptococcus, Coccidioides, Mucor)

Viruses {Influenza, Hepatitis (A,B,C), HIV, Rubella, Herpes simplex virus (HSV), Herpes Zoster (VZV), Cytomegalovirus (CMV), Epstein barr virus, Respiratory Syncytial Virus)} Rickettsia (Rocky Mountain Spotted Fever, Q fever) Spirochetes (Treponema pallidum) Protozoa (Pneumocystis carinii, Toxoplasma gondii)

Pathogens and their Sites

Antibiotics

Beta-Lactams Penicillins Cephalosporins Carbapenems Aminoglycosides Quinolones Macrolides (and Ketolides) Monobactam Carbapenems Glycopeptides Tetracyclines Miscellaneous Agents

Trimethoprim/Sulfamethoxazole
(Bactrim)

Clindamycin (Cleocin)

Metronidazole (Flagyl)
Quinupristin/dalfopristin
(Synercid)

Linezolid (Zyvox)
Daptomycin (Cubicin)

Penicillins
Natural
Antistaphylococcal Aminopenicillins Antipseudomonal Beta-lactamase inhibitor combinations

Penicillins
Mechanism of Action: bactericidal, inhibit bacteria cell wall synthesis,
reducing cell wall stability, thus causing membrane lysis.

Adverse Effects: Hypersensitivity reactions - maculopapular rash, anaphylaxis, serum

sickness (fever, malaise, joint pain 7-10 d post therapy) Gastrointestinal - diarrhea esp. ampicillin. Pseudomembranous colitis from clostridium. Local reactions - IM-pain, redness at injection site/IV phlebitis, burning and redness Hepatotoxicity - in LFTs, hepatitis (rare)-most common w/oxacillin. Nephrotoxicity - interstitial nephritis (rare), most common with methicillin Platelet dysfunction-most common with carbenicillin and ticarcillin Neurologic - encephalopathy, seizures (rare) - with high doses & renal insufficiency "procaine reactions" - anxiety, psychosis, feeling of impending doom Electrolyte abnormalities- K+ with ticarcillin and carbenicillin; Na with ticarcillin and carbenicillin

Natural Penicillins
Penicillin G (IV, IM) Procaine Penicillin G (IM) Benzathine
Penicillin G (IM), Penicillin V (PO) Good coverage: narrow spectrum = some Gm + and - cocci
(streptococci, pneumococci, enterococci, meningococci), grampositive rods (corynebacteria, L.monocytogenes), spirochetes (Leptospira sp., Treponema sp., Borrelia sp.), and most of anaerobes (peptostreptococci, clostridial species, Actinomyces, not B. fragilis).

Poor Coverage: Staph, Gm (-), GI anaerobes Uses: low-dose = pseudomembranous tonsillitis, strept throat,
streptococcal skin infections (impetigo), or animal bite and scratches. High-dose = endocarditis (caused by viridans streptococci or enterococci), streptococcal, pneumococcal or meningococcal sepsis, clostridial wound infection.

Antistaphylococcal
Nafcillin (IV), Oxacillin (IV),Dicloxacillin (PO), Methicillin (no
longer used to treat infections)

Methicillin (used for sensitivity/resistance testing): MRSA and ORSA Good coverage: narrow spectrum, active against beta lactamase
producing Staph aureus (MSSA)

Poor coverage: enterococci, Staph epi (many strands are resistant),

Gm (-), anaerobes. No MRSA coverage.

Uses: skin/soft tissue (cellulitis), endocarditis, osteomyleitis

Aminopenicillins
Ampicillin (IV, PO), Amoxicillin (PO)
Expanded gram (-) activity Good coverage: H. infl, enterococcus (non-VRE),
Listeria, Proteus, Streptococci (HELPS) Neisseria spp & E. coli

Poor coverage: Staph, Pseudomonas, GI anaerobes Uses:

Amp = UTIs, Amox = URIs (sinusitis, bronchitis & otitis media)

Antipseudomonals (extended-spectrum)
Mezlocillin, Piperacillin, Carbenicillin, Azlocillin, Ticarcillin (MPCAT)
Piperacillin and Ticarcillin (IV) only agents available in U.S Good coverage: Pseudomonas (pip>azlo>mezlo=ticar>carben),
Klebsiella, Ecoli, Proteus, Enterobacter spp.,enterococcus (piperacillin) and anaerobes

Poor coverage: Serratia spp (may be resistant)

Uses: Nosocomial infections, usually used in combo with lactamase inhibitors

Mezlocillin Piperacillin Carbenicillin

Azlocillin
Ticarcillin

Beta-lactamase inhibitor combinations

Enhanced coverage against -lactamase producing organisms,
MSSA, anaerobes

Amoxicillin-clavulanic acid (Augmentin) Otitis media, uti's, upper rti's, skin/soft tissue infections, sinusitis, Ampicillin-sulbactam (Unasyn) Polymicrobial infection (no pseudo.) intra-abdominal, utis,
anaerobes

Ticarcillin-clavulanic acid (Timentin) Polymicrobial infections, nosocomial infections, pseudomonas,

anaerobes, diabetic foot ulcers

Piperacillin-tazobactam (Zosyn) Polymicrobial infections, nosocomial infections, anaerobes pseudomonas, intra-abdominal (enterococcus)

Cephalosporins
Mechanism of Action - similar to penicillins
Adverse effect: Hypersensitivity reactions (~ 0.5 - 2% cross reactivity between
cephalosporins and penicillins) rash, fever, eosinophilia-most common, hives and anaphylaxis rare Gastrointestinal - Bile stasis (ceftriaxone), avoid in neonates w/ hyperbilirubinemia Interfere w/ urine glucose test (cefixime,ceftazidime, cefepime) Hematologic reactions - hypoprothrombinemia & increase risk of bleeding, with drugs which have NMTT side chain (cefotetan, cefoperazone) disulfiram reaction (flushing, hypotension, palpitations, chest pain, HA, weakness) when alcohol is ingested

Cephalosporins 1st Generation

ORAL AGENTS Cephalexin (Keflex) Cephradine (Velosef) Cefadroxil (Duricef)
PARENTERAL AGENTS Cephalothin (Keflin) Cefazolin (Ancef ,
Kefzol)

CLINICAL USE Gm (+) coverage (including

pcnase-producing strains) and Gm (-) bacilli (P. mirabilis, E. coli, K. pneumoniae) PEK Cephalexin and and cephradrine are the most effective for skin infections, UTIs & surgical prophylaxis

*all start with ceph- except cefadroxil and cefazolin

Cephalosporins 2nd Generation

ORAL AGENTS Cefaclor (Ceclor) Cefuroxime axetil (Ceftin ) Cefprozil (Cefzil) PARENTERAL AGENTS Cefoxitin (Mefoxin) Cefuroxime axetil (Zinacef ) Cefotetan (Cefotan) CLINICAL USE Most important is activity
against H. influenza and M. catarrhalis (including beta lactamase producing strains). RTIs Cefaclor useful in otitis media and sinusitis for PCN allergic pts. Cefotetan, cefoxitin - mixed aerobic-anaerobic infections (intra-abdominal infections) Cefuroxime for CAP Extended gram (-) spectrum HENPEK (H. influenza, E. coli, N. gonorrhea , Proteus, Enterobacter, Klebsiella)

*all start with cef- and lack one, en, or ime ending (except cefuroxime, ceftaroline, cefdinir)

Cephalosporins 3rd Generation

ORAL AGENTS Cefixime (Suprax) Cefpodoxime (Vantin) Ceftibuten (Cedax) Cefditoren (Spectracef) Cefdinir (Omnicef)

PARENTERAL AGENTS Ceftazidime (Fortaz , Tazicef) Ceftriaxone (Rocephin) Cefotaxime (Claforan) Ceftizoxime (Ceftizoxime)

CLINICAL USE Expanded activity against Gm

(-) HENPEKS (include Serratia spp) Generally used to treat C.A.P Valuable in the treatment of meningitis (penetrate CSF), STDs, Antipseudomonals (nosocomial infections) ceftazadime > cefoperazone Ceftriaxone, cefotaxime has good activity vs streptococci including PCN resistance

* all start with cef- end in ime, one, or en except cefuroxime (2nd), cefepime (4th), ceftibuten,

Cephalosporins 4th Generation

Cefepime (Maxipime)

Expanded activity against Gm (-) HENPEKS (Enterobacter spp) Activity against pseudomonas (similar to ceftazidime) Activity against streptococcus (similar to ceftriaxone) Indicated for febrile neutropenia and nosocomial infections Meningitis: comparable cure rate to ceftriaxone and cefotaxime

Cephalosporins
Ceftaroline (Teflaro)

th 5 Generation

Activity against Gm (-) and many resistant Gm (+) bacteria

including MRSA Indicated for CAP and skin and subcutaneous infections (MSSA & MRSA) Does not cover pseudomonas

Cefotaxime Maxipime (cefepime)

Cefuroxime

Ceftriaxone

Ceftazidime

Carbapenems
Imipenem/Cilastatin (Primaxin), Meropenem (Merem), Ertapenem
(Invanz), Doripenem (Doribax)

Mechanism of Action: Bactericidal inhibitor of cell wall synthesis.

Beta-lactams with very broad-spectrum. Clinically used for serious mixed infections: soft tissue & intra-abdominal gram

positive, gram negative, aerobic and anaerobic bacteria. Only Meropenem indicated in bacterial meningitis in children > 3 months Doripenem, Meropenem and imipenem are active against pseudomonas aeruginosa (Not ertapenem) Ertapenem has a long half life; hence once daily dosing. Doripenem is newest agent, similar spectrum to imipenem and meropenem

Adverse Effects:
Hypersensitivity-rash, fever, pruritis approx. 15 - 20% cross sensitivity with
penicillins. Questionable, recent studies suggest most may tolerate Seizure - <1% with Imipenem and 0.5% with ertapenem associated w / renal failure, advanced age, higher doses and underlying CNS disorders. (increase risk w / Acyclovir and Ganciclovir) Meropenem - appears less likely to call seizures Nausea and Vomiting

Aminoglycosides
Gentamicin
Tobramycin

Amikacin
Streptomycin

Netilmicin
Neomycin

Aminoglycosides
Mechanism of Action: bactericidal, inhibit bacterial protein
synthesis by impeding the function of the 30s ribosomal subunit.

Adverse Effects: Nephrotoxicity 5-15%, vestibular & cochlear 2-15% (>amikacin)

toxicity associated with aminoglycosides

Pharmacokinetics: Traditional Dosing (2-3mg/kg/day divided over q8-12).

Gentamicin / Tobramycin - Peaks (5-10 mcg/ml) Trough (<2 mcg/ml) synergy (1mg/kg/dose). Amikacin traditional dosing (7.5 - 10 mg/kg/dose q12). Amikacin peak (20 - 30 mcg/ml) Trough (< 4 mcg/ml). Once-daily Dosing: Gentamicin / Tobramycin (4-7 mg/kg/day) Once-daily Dosing: Amikacin (15 mg/kg/day)

Traditional Dose Monitoring

Draw levels off the third dose for:
-Patients with normal renal function based on Creatinine/Bun, I/O's, medical history; concomitant drug therapy, and hydration status. When to draw levels: Aminoglycoside: Peak/trough: 30 minutes before and after a 30 minute infusion.

Draw levels off the first dose for:

- Patients with abnormal renal function based on BUN/SCR; I/O's, edema, history of renal or cardiac disease. - Patients receiving other nephrotoxic drugs. - Patient is neutropenic, febrile, and/or unstable. - Patient has unstable or increasing serum creatinine. When to draw levels: 1st level: aminoglycoside: 30 minutes post infusion. 2nd level: at least one half-life (depending on drug) after the 1st level.

Clinical Use
Excellent Gm (-) coverage, including pseudomonas
Gm (+) coverage: only with beta-lactams as a low dose
synergistic addition vs. enterococcus

Amikacin- has the broadest spectrum

Streptomycin - used to treat plague and tularemia

Neomycin - useful for perioperative bowel sterilization

Once Daily Dosing

Alternative dosing method which may be less
nephrotoxic than conventional dosing with similar efficacy.

Based on the concentration-dependent kill

characteristic of aminoglycosides.

At approximately 10 times the minimum concentration

necessary for inhibition of bacterial growth, maximal antimicrobial activity is observed

Used for the treatment of gram negative infections

Exclusion criteria:
Elderly (age 70 years)
Pregnancy or post-partum Renal insufficiency (CrCL<
30 ml/min)

Endocarditis
Synergy for gram positive
infections

Cystic fibrosis

Dialysis
Severe liver disease or
ascites

Surgical prophylaxis
Severe fluid overload states Extensive burns (> 50% total
body surface area)

History or signs of hearing

loss or vestibular toxicity

Determine patients dosing weight (DW)

Non-Obese patients: Use ideal body weight (IBW) unless total body weight (TBW) is less. IBW (males) = 50 kg + (2.3 x height in inches > 60 inches) IBW (females) = 45 kg + (2.3 x height in inches > 60 inches) Obese patients: Use adjusted body weight (ABW) in obese patients (TBW > 30% over
IBW)

ABW (kg) = IBW + 0.4 (TBW IBW) Determine patients dose (round to nearest 20 mg for gentamicin/tobramycin and to nearest 100 mg
for amikacin)

Gentamicin / Tobramycin 4 to 7 mg/kg x DW Amikacin 15 to 20 mg/kg x DW

Dosing Interval Methods (once daily dosing)

Serum concentration monitoring

Aminoglycoside trough monitoring

Nomogram monitoring

Creatinine Clearance Monitoring

Creatinine Clearance Dosing Interval mL/min > 60 Q24h 40-59 Q36h (pre-dose level recommended) or conventional
aminoglycoside dosing suggested

< 40 Use conventional aminoglycoside dosing & take two post-levels

to determine appropriate interval

Twice weekly serum creatinine measurements are recommended to

assess renal function.

For patients with a CrCl < 60 mL/min, a pre-dose aminoglycoside level

may be warranted to ensure that levels are negligible (< 1 mg/L) at the end of the dosing period. Levels can be drawn prior to second or third dose. Baseline and weekly audiometry and the E-test are recommended for patients who require greater than 2 weeks of aminoglycoside therapy.

Serum Concentration Monitoring

Use trough levels (peak levels NOT routinely monitored):
Trough concentrations should be checked 30 to 60 minutes prior to the
next (second) dose. Desired levels:

Gentamicin / tobramycin < 0.5 mcg/mL Amikacin < 2.5 mcg/mL

If level is greater than desired trough, extend dosing interval by 12 hours
and repeat level prior to next dose (or use conventional dosing and monitoring methods). If the next level continues to be high, then change to conventional dosing method.

Repeat level weekly AND with any significant changes in renal function.
Serum creatinine should be monitored every 1-3 days.

Nomogram Monitoring

In some patients, nomograms often do not accurately predict the correct dose or dosing interval. Therefore, selective pharmacokinetic monitoring may be required.

Quinolones
1st Generation: Norfloxacin (Noroxin) (PO, OPTH)
2nd Generation: Ciprofloxacin (Cipro) PO, IV),
Ofloxacin (Floxin) (PO, IV, Otic, OPTH)

3rd Generation: Levofloxacin (Levaquin) PO, IV, Top)

4th Generation: Moxifloxacin (Avelox) (PO),
Gemifloxacin (Factive) (PO)

Quinolones
Mechanism of Action: bactericidal, via inhibition of DNA gyrase. Adverse Effects: CNS effects-dizziness, headaches etc. < 3% Gastrointestinal effects - nausea, diarrhea Photosensitivity < 2-4%, 7.9% Sparfloxacin-sunlight or artificial UV light QTc interval prolongation, torsades de pointes Cartilage toxicity in pediatrics/pregnant and lactating women. Probably
safe in children if other alternatives are not available (Cystic fibrosis) Black Box Warning: Tendonitis/tendon rupture (esp in elderly, corticosteroid use, pts w/ kidney/heart/lung/ transplant)

Drug Interactions: Multivalent cations (Mg, Al, Zn, Fe etc.) up to ten fold reduction in serum
level Cytochrome P450 - Ciprofloxacin > Ofloxacin/Lomefloxacin Theophylline/caffeine - no interaction with norfloxacin, ofloxacin, Avoid using w/drugs that may prolong QT interval (i.e. terfenadine, astemizole, erythromycin, quinidine, procainamide, TCA's)

Clinical Use
Gram negative (excellent) Cipro potent vs P.
aeruginosa Excellent activity against Enterobacteriaceae Used in Gm (-) osteomyelitis, bacteremia, gastroenteritis & utis Useful in complicated utis

Atypical Chlamydia, M. pneumoniae,

Legionella

Other pathogens Mycobacteria: M. avium

complex (Cipro), M. Tuberculosis MDRT (ofloxacin/levofloxacin) STD pathogens: C. trachomatis (ofloxacin), N. gonorrhea Enteric pathogens: E. Coli, Campylobacter, Salmonella, Shigella

Gm positive (variable) Third and fourth

generation good strept. Pneumoniae activity = respiratory quinolones Moderate activity against staphylococci (MSSA) Poor to moderate activity vs. enterococci

Macrolides
Erythromycin (E-Mycin, Eryc) (PO, IV, OPTH)
Clarithromycin (Biaxin) - (PO) Azithromycin (Zithromycin) (PO, IV) Telithromycin (Ketek) Ketolide (PO) Fidaxomycin (Dificid) (PO)

Macrolides
Mechanism of Action: bacteriostatic; they bind to the 50s ribosomal
subunit, inhibiting bacterial protein synthesis.

Adverse Effects: Gastrointestinal-gastric stimulant, iv or po. (erythro, clarithro,

telithro) Cholestatic hepatitis-with erythromycin estolate Ototoxicity with high doses (erythromycin, azithromycin)

Drug Interactions Cytochrome P450 active agents (theophylline, carbamazepine,

rifabutin, protease inhibitors) primarily erythromycin, clarithromycin and telithromycin (3A4)

Clinical Use

Gram-positive bacteria Good activity against grampositive organisms, including streptococci, and corynebacterium and Neisseria Some staphylococcus, azithromycin is less active, as a result these agents are microbiologically inferior to dicloxacillin, first gen cephalosporins and clindamycin in skin and soft tissue infxns. Clarithromycin is more active than erythromycin vs. staphylococci and streptococci Gram-negative bacteria Erythromycin has poor-moderate activity vs. H. influenzae Azithromycin and telithromycin are more active against H. influenzae.

Atypical bacteria: Most macrolides have excellent activity vs. atypical respiratory pathogens, including Legionella, Mycoplasma and Chlamydia Other pathogens: Clarithromycin and azithromycin active vs. Helicobacter pylori & M. avium complex. Azithromycin is efficacious in single-dose treatment of uncomplicated chlamydia cervicitis and urethritis Fidaxomycin used to treat C. difficile only (narrow spectrum) 1st line - Bartonella henselae (cat scratch bacillus), Bordetella pertussis (whooping cough)

Monobactams
Aztreonam (Azactam)- bactericidal, inhibits cell wall synthesis Aztreonam does not cross react with PCNs or CEPHS Aerobic gram negatives only Moderate activity against Pseudomonas aeruginosa and
Enterobacter spp. No gram positive or anaerobic activity New inhaled formulation approved for cystic fibrosis

Adverse Effects: Hypersensitivity - rash Usually safe to use in pts w/ PCN

allergy but AVOID in pts w/ ceftazidime allergy (similar side chain) Gastrointestinal - Nausea, vomiting and diarrhea

Glycopeptides
Vancomycin and Telavancin (Vibativ) -1st lipoglycopeptide in US Mechanism of Action: bactericidal; inhibits bacterial cell wall
synthesis. Telavancin has additional MOA that involves disruption of membrane potential and changing cell permeability and bactericidal activity is concentration dependent unlike vancomycin.

Pharmacokinetics Vancomycin therapeutic peaks (20 - 40 mcg/ml / troughs 5 - 15

mcg/ml) Telavancin no blood level monitoring necessary Toxicity "Red Man Syndrome" RMS-seen with rapid infusion (infuse both over 60 mins). Fever, chills, phlebitis, rash, and reversible leukopenia. Ototoxicity - rare if levels < 40 mcg/ml, nephrotoxocity ~ 5% Telavancin may prolong QT interval Black Box Warning with Telavancin: Prior to use, women of childbearing potential should have a serum pregnancy test. Caused fetal malformations in animals.

Clinical Uses
Gram-positive: All including methicillin sensitive and
methicillin-resistant Staphylococci and enterococcus (problems with vancomycin resistant enterococcus)

Vancomycin - skin/soft tissue/bone infections and line

sepsis, 2nd line for C. difficile colitis (PO)

Televancin - complicated skin/soft tissue infections

Gram-negative: none

Tetracyclines
Demeclocycline (Declomycin) (PO)
Doxycycline (Adoxa, Doryx, Monodox,
Vibramycin, Oracea, Periostat) (PO, IV)

Minocycline (Minocin, Solodyn) (PO)

Tetracycline (Sumycin) (PO)

Tigecycline (Tygacil) - (IV)

Tetracyclines
Mechanism of Action: Bacteriostatic, inhibits bacterial protein
synthesis via binding to the 30S ribosomal subunit

Adverse Effects: Photosensitivity, hepatotoxicity, GI intolerance

(diarrhea, nausea, anorexia), Contraindicated in pregnancy and children < 8y/o (tooth discoloration and interference with bone growth), Fanconi Syndrome with expired tetracycline Abx

Minocycline (Lupus-like symptoms, vertigo, skin

pigmentation)
Drug Interactions: Avoid use with divalent or trivalent cations. Do
not take concomitantly with milk or dairy products

Clinical Use
Broad spectrum, some gram (+), largely gram (-). ricketssial
infections, and atypical bacteria (Chlamydial infections, M. pneumoniae) Doxycycline - 1st line for Rickettsia rickettsii (Rocky Mountain spotted fever) and Borrelia burgdorferi (Lyme Disease), plague

Mainly used PO MOA: inhibits bacterial protein synthesis (30s subunit) Tigacycline: Structure (glycylcycline) helps it to be more effective
against bacterial resistance

Tigacycline: IV only, good activity against MRSA, VSE

Trimethoprim/Sulfamethoxazole (Bactrim)
Mechanism of Action: usually bactericidal, sulfamethoxazole inhibits the
formation of dihydrofolic acid from PABA. Trimethoprim inhibits dihydrofolate reductase, thus blocking bacterial synthesis of folic acid.

Active against gram positve organisms: S. aureus, S. epidermidis, S.

pneumoniae

Active against gram negative organisms: E. coli, enterobacter, P. mirabilis,

Klebsiella spp., Serratia, Shigella, Neisseria spp.

Other organisms: Pneumocystitis carinii, Nocardia asteroides.

1st line for Stenotrophomonas Maltophilia (formerly Xanthomonas) and

Tropheryma whippeli (Whipples Disease)

Clinical uses: uncomplicated utis, acute gonococcal urethritis, acute

exacerbation of chronic bronchitis, shigella, and salmonella infections, and PCP prophylaxis.

Adverse effects: Rash, pruritis, thrombocytopenia, nausea and vomiting Drug interactions: several including clarithromycin, warfarin, phenytoin

Clindamycin (Cleocin)
Mechanism of Action: bacteriostatic, binds to 50s ribosomal
subunit, thereby suppressing bacterial protein synthesis.

Gram positive organisms (Staph & Strept) and anaerobes (both

gm (+) and gm (-) ) also toxoplasma gondii & pneumocyctis carinii pneumoniae (PCP)

NO activity vs gram negative bacteria. Clinical uses: Staph infections, Intra-abdominal anaerobic
infections, bacterial vaginosis, aspirational pneumonia, and third line to PCN allergic patient intolerant of erythromycin, acne (topical)

Adverse effects-GI disturbances - N/V, pseudomembranous

colitis / increase in LFTs

Metronidazole (Flagyl)
Mechanism of Action: amebicidal, bactericdal, and
trichomonicidal. Inhibits bacterial nucleic acid synthesis.

Adverse effects and Drug interaction: GI disturbances-metallic taste, nausea, abdominal

cramping Mutagenic and carcinogenic - avoid in 3rd trimester of pregnancy Discoloration of urine-reddish-brown Drug interactions-alcohol (disulfiram rxn), increase bleeding w / warfarin.

Clinical Uses
Active against all anaerobic cocci and anaerobic gram-negative
bacilli (Bacteroides spp, & Fusobacterium)

Preferred agent in amebic dysentery, giardiasis, and

trichomoniasis.

D.O.C. for clostridium difficile colitis

Poor vs. gram-positive and gram negative aerobes Uses
Anaerobic infections Bacterial vaginosis C. diff colitis Parisitic infections H. Pylori - PUD (eradication, some resistance)

Quinupristin/dalfopristin (Synercid)
Mechanism of Action: dalfopristin inhibits early protein synthesis in
the bacterial ribosome while quinupristin inhibits late phase protein synthesis

Active against VREF (vancomycin-resistant Enterococcus faecium

only, not active against E. faecalis), S. aureus, S. pneumoniae, Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S. epidermidis (MRSE). May also be active against N. meningitidis, M. catarrhalis, Legionella pneumophilia, M. pneumoniae and Clostridium perfringens.

IV only ADRs include pain and inflammation at injection site, edema,

thrombophlebitis. Arthralgias and myalgias are common and may be severe.

Watch for drug interactions, is a potent inhibitor of CYP3A4

Linezolid (Zyvox)
Mechanism of Action: inhibits protein synthesis at the bacterial
ribosome.

Active against VRE (vancomycin-resistant Enterococcus faecium

also active against E. faecalis), S. aureus, S. pneumoniae, Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S. epidermidis (MRSE)

No activity against gram negative organisms

P.O and I.V formulation available

Generally well-tolerated, most common side effects are diarrhea,
nausea, and vomiting. If therapy last longer than 2 weeks, monitor platelets.

Daptomycin (Cubicin)
Mechanism of Action: binds to bacterial cell membranes and
causes cell death by inducing rapid depolarization of the membrane potential, leading to disruption of DNA, RNA, and protein synthesis

Active against VRE (vancomycin-resistant Enterococcus faecium

also active against E. faecalis), S. aureus, S. pneumoniae, Methicillin-resistant S. aureus (MRSA) and Methicillin-resistant S. epidermidis (MRSE)

No activity against gram negative organisms Alternative to other agents (eg, linezolid, quinupristin/dalfopristin)
for treating infections caused by MRSA & VRE

Serious ADRs include: Asthmatic eosinophilia, renal failure, and

rhabdomyolysis