ESSENTIALS OF ANTIBIOTICS

Jeanne M. Farnan, MD MHPE

Assistant Professor
Section of Hospital Medicine
University of Chicago
Adult Hospitalist Physician Assistant and Nurse
Practitioner Boot Camp

Learning Objectives
Identify factors to consider when choosing
antibiotics
Determine appropriate antibiotics for organism
Describe basic antimicrobial spectra of
common antibiotics
Identify patients at risk for pseudomonas and
MRSA
Recognize important side effects of antibiotics

Selection Considerations:
#1. Spectrum

Time-dependent kinetics
(beta-lactams, vancomycin)

Time spent at the binding sit

inhibition of bacterial growth

Concentration-dependent
kinetics (aminoglycosides,
FQs)

Concentration must meet certain

level for effectiveness

http://www.antimicrobe.org/history/PK-PD%20Quint.asp

Selection Considerations:
#2. Tissue Penetration
Antibiotic-specific properties (e.g. lipid
solubility)
Tissue-specific properties (e.g. adequacy of
blood flow, presence of inflammation)
Acute vs. chronic infection
Organism-specific properties

Intra-cellular

pathogens

Cunhe, Burke 2007. Antibiotic Essentials

Selection Considerations:
#3. Antibiotic Resistance

Natural vs. acquired

Pathogens

not covered by the usual spectrum of an

antibiotic (25% of S. pneumonia are naturally
resistant to macrolides)
Acquired resistance-previously sensitive pathogen
NO LONGER sensitive (ampicillin-resistant H.
influenzae)

Intermediate vs. High-level resistance

Cunhe, Burke 2007. Antibiotic Essentials

Selection Considerations:
#3. Antibiotic Resistance

ESBL (Extended-spectrum beta-lactamases)

Klebsiella

species
Risk factors: ICU and length of stay, severity of
illness, lines

MRSA
HA-MRSA

vs. CA-MRSA

Selection Considerations:
#4. Cost
Early IV to PO conversion SINGLE biggest cost
saving
Choosing mono-therapy when appropriate
Consider patient factors:

Insurance

coverage
Non-adherence with increased frequency of dosing

Dosing considerations

Renal insufficiency:
R.O.T:
If

CrCl 40-60cc/min, decrease daily dose by 50%

If CrCl 10-40cc/min, decrease daily dose by 50% AND
double dosing interval

Hepatic insufficiency:
R.O.T

decrease daily dose by 50% OR use renally

cleared drug

Cunhe, Burke 2007. Antibiotic Essentials

Other considerations:
Bacteriocidal vs. Bacteriostatic

MUST use BACTERIOCIDAL agent for:

Endocarditis
Bacterial

meningitis
Neutropenic fever

Bacteriocidal agents:
Beta-lactams,

FQ, vancomycin, aminoglycosides,

rifampin, flagyl

Bacteriostatic agents:
Erthryomycin,

tetracycline, clindamycin

Class: Beta-lactams

Mechanism attack cell wall synthesis bacteriocidal

Includes:

PCN AKA narrow-spectrum, semi-synthetic PCN

[methacillin/oxacillin], carbapenems and cephalosporins

Penicillin:
Meningococcus, most Strep, anaerobes
Still drug of choice for many infections including:

Periodontal infxns, PCN-sensitive S. pneumoniae, viridans Streptococci,

group A/B strep, syphyllis

Class: Beta-lactams

Ampicillin/Amoxicillin AKA extended spectrum

PCNs:
PCN

+ some GNR coverage [E. coli, H. flu,

Salmonella, Shigella]
D.O.C for Listeria, susceptible UTI [Proteus] and
Enterococcus

Semi-synthetics (methicillin/oxacillin):
PCN-ase

resistant
Limited spectrum with rising MRSA
Still some utility with susceptible cellulitides

Class: Beta-lactams

Anti-pseudomonal PCN
[ureidopenicillins]
More

GNR [Pseudomonas], anaerobes and

Acinetobacter

Beta-lactamase inhibitors
NO

antibacterial activity independently

Sulbactam

[with Ampicillin= Unasyn]

Tazobactam [with Pipericillin= Zosyn]
Clavulanate/Clavulonic acid

Class: Beta-lactams
Cephalosporins
PCN-ase resistant
NO activity against Enterococci,
MRSA

1st generation AKA cefazolin

Great

gram+ activity
Most staph, strep, common
anaerobes
Skin/soft tissue, surgical prophylaxis

Class: Beta-lactams
Cephalosporins

2nd generation:
Less

active against GPC, more against GNR

H. flu activity
Cefuroxime

Bacteroides activity
Cefoxitin,

Cefotetan

PID, prophylaxis for GI/GYN surgery

Class: Beta-lactams
Cephalosporins

3rd generation:
Stability

to common beta-lactamases
More reliable CNS penetration
N. gonorrhea, H. influenza
Activity against Psuedomonas
Ceftazidime

Poor

activity against Psuedomonas

Ceftriaxone,

Ceftizoxime, Cefotaxime

Class: Beta-lactams
Cephalosporins

4th generation:
Cefepime = GN activity
of 1st generation
Seizure

of 3rd generation and GP

threshold

5th(!) generation:
Ceftobiprole

= Cefipime + Enterococcus

Activity

against Enterobacter and Enterococcus

Investigational activity against MRSA
Ceftaroline
CABP,

ABSSSI (MRSA!)

Class: Beta-lactams
Cephalosporins

Carbapenems:
B.

fragilis, Enterobacter, Pseudomonas

Irtapenem: no activity against Pseudomonas or
Acinetobacter
SIDE EFFECTS!

Monobactams AKA Aztreonam:

ONLY

GN activity
Enterobacter and Pseudomonas but NOT GPC

Cyclic Peptides

Glycopeptides AKA Vancomycin:

In

general is BACTERIOCIDAL

Most

GP, including MRSA

PCN-resistant

Infusion-related reactions
Red

pneumococcus

Man syndrome

Nephrotoxicity

Macrolides

Erythromycin: atypical pneumonia, Strep.

pneumo
S.

pneumo demonstrating increasing macrolide

resistance

Newer agents broader atypical coverage

Enhanced

GN coverage
Azithomycin= better H. flu coverage, MAI
Clarithromycin= MAI
Telithromycin
Severe

visual disturbance, hepatotoxicity

Sulfas/Lincomycins

Trimethoprim/sulfamethoxizole
Second

most common ALLERGY

Bacterio-STATIC
Enterobacter, Chlamydia
PCP!

Clindamycin
GP

aerobes, GN anaerobes
CA-MRSA
DOC

for pneumonia, septic arthritis, and osteo IF isolate is

susceptible and the D-test is negative

Neutropenia/thrombocytopenia

Aminoglycosides

GN!!
Septicemia,

complicated UTI/URI

Require AEROBIC metabolism of cell to be effective

so NO ANAEROBE coverage
Gentamicin, tobramycin, amikacin
Infrequent emergence of resistance BUT:
Narrow

therapeutic window
Renal/oto-toxicity

FQs
GN coverage, including GNR
NOT good against anaerobes
CIPRO [2nd gen FQ] only intermediate GP
activity so NOT good choice for empiric CAP
coverage
NOT for pediatric population [FDA <18y/o]
QT prolongation

Tetracyclines

Aerobic GPB/GNR/GNB [Vibrio, H.flu]

Activity against many atypical pathogens:
Spirochetes
Mycoplasma
Chlamydia

Populations (NO pregnant women or children under 8

y/o)
BIG adverse reactions/side effects:
Photo sensitivity
Dose-related GI upset
Hypoplasia of teeth enamel

and the rest

Flagyl
Anaerobic

and GN coverage

C.

diff!
WBC suppression
Pertinent anti-fungals
Imidazoles

(skin flora, Trichomonas)

Triazoles
Fluconazole:

Candida species
Voriconazole: invasive aspergillus, extended or resistant
Candidal species

MRSA treatment

Linezolid
Nosocomial

pneumonia AND CSSSI

Safety concerns:
Notably

serotonin syndrome, thrombocytopenia, lactic

acidosis and ocular toxicity

Tigecycline
CSSSI

and complicated intra-abdominal infections

Difficult to use as outpatient 2nd of instability of
preparation

MRSA treatment
Resistant to ALL beta-lactam agents
Vancomycin

Remains

agent of choice
Most clinical experience

Daptomycin
Approved

for CSSSI
Clinical success rate similar to vancomyin

What about VRE??

Risk factors:
Previous

hospitalization/long term care

Patient factors
Length

of stay
Hardware
ICU stay
Previous

antibiotic use

Colonization pre-dates infection

Patients

who are colonized have ~8% rate of

developing a VRE infection in-hospital or after
discharge

VRE treatment

Vancomycin-resistant E. faecalis
Demonstrated

Sinercid:
ONLY

susceptibility to beta-lactams

enterococcus faecium

Covers both faecium and faecalis

Linezolid

(thrombocytopenia)
Daptomycin (myopathy, serial CKs)
Tigecycline (N/V, unstable prep for outpatient)

Pseudomonas aeruginosa

Predilection for immunocompromised hosts

Neutropenic

fever

Notoriety now associated with VAP

Treatment:

REMOVAL

of hardware

TIME
Mono-therapy

vs. combination therapy

Pseudomonas therapy

Mono-therapy vs. combination therapy

AG

+ extended spectrum anti-pseudomonal PCN

OR cephalosporin
Greater

spectrum of activity

Inhaled therapy (e.g. colistin) for special

populations

FINALLY.cases
Cellulitis
Diagnosis?

Imaging,

Organisms?
Group

gram stain/culture of drainage

A strep, MRSA, Staph aureus

Treatment?
r/o

MRSA, Nafcillin IV, 1st gen cephalosporin

Cases.

Community-acquired pneumonia
Diagnosis?

PA/lateral CXR, sputum/blood cultures, bronchoscopy with

BAL, thoracentesis for parapneumonic effusion

Organisms?
CAP: S. pneumo, mycoplasma, chlamydia
Other: resistant s. pneumo, pseudomonas, staph aureus,
anaerobes, enteric GN

Treatment?
CAP: azithro/ceftriaxone, levaquin
Aspiration: clindamycin
Nosocomial: pseudomonal coverage

Cases
Urinary Tract Infection
Diagnosis?

U/A

with micro/culture

Organisms?
Enteric

GNR, Proteus, Enterococci

Treatment?
Consider

FQ (cipro), sulfas

Cases
Bacterial Meningitis
Diagnosis?

LP

opening pressure >180mm, WBC>10/uL,

glucose<40, protein>45mg/dL

Organisms?
S.

pneumo, N. meningitidis, H. flu, Listeria

Treatment?
Decadron

0.4mg/kg IV
Ceftriaxone 2gm IV q12 and Vancomycin 1gram IV
q6
Ampicillin for high suspicion for listeria, >55y/o,
immunocompromised

Infection & Choice of Antibiotic

Infection & Choice of Antibiotic

Skin and Soft Tissue Infections
Pneumonia
Intra-abdominal Infections
Urinary Tract Infections

Skin & Soft Tissue Infections

Organisms

MRSA!

Most infections are caused by Staph aureus or

Streptococcus spp.
MRSA is the most common cause of suppurative skin
infections in the U.S.

In individuals with DM2, decubitus ulcers, or

surgical wounds, poly-microbial infections with
Gram negative organisms are common

Skin & Soft Tissue Infections

Antibiotic Coverage

Community-acquired MRSA (not HA-MRSA) can

often be covered with Bactrim, Doxycycline or
Clindamycin
Vancomycin for uncomplicated infections
Zosyn/Cefepime can be added for complicated
infections
If susceptibilities are obtained, tailor accordingly

Pneumonia

Organisms

Community Acquired

S. pneumo (haemophilus, moraxella) and atypicals

(Mycoplasma, Chlamydia, Legionella)

Hospital Acquired/Healthcare-associated

Nursing home patients and patients in the hospital >4872 hours (Exception is legionella)
S. pneumo, Staph, and Gram negatives (Klebsiella,
Pseudomonas)
Anaerobes in patients at risk for aspiration

Pneumonia

Antibiotic Coverage

CAP

Respiratory fluoroquinolone (e.g. Moxifloxacin)

Check QTc if prolonged, can cause Torsades
Benefit: Has anaerobic coverage (Moxi only)
Ceftriaxone and Azithromycin
No anaerobic coverage

HAP

Vancomycin
Pip/Tazo or Cefepime or Carbepenems (Cefepime no
anaerobic coverage)

Intra-abdominal Infections

Organisms

Enteric Gram negatives

Enterococci
Anaerobes

E. coli, Pseudomonas, Klebsiella, Proteus

B. fragilis

Fungal (usually related to perforation)

CDAD (C. difficile-associated disease)

Intra-abdominal Infections

Antibiotic Coverage

Empiric therapy should cover probably

Pseudomonas and anaerobes
No immediate need for anti-fungals unless
perforation is suspected or pt does not respond to
initial management

Anti-pseudomonal penicillin (Pip/Tazo)

Fluoroquinolone (Cipro only FQ that covers
Pseudomonas)
Anaerobic coverage (Flagyl)

C. difficile

C. difficile produces two toxins, A and B

PCR new gold standard High sens/spec!
Stool assay is not very sensitive

If your clinical suspicion is high enough and stool is

negative empiric treatment is fine

Treatment

Flagyl (PO and IV)

Vancomycin (PO)
Antibiotics should ideally be given PO

Urinary Tract Infections

Organisms

E. coli, Proteus spp, and other Gram negative rods

S. saprophyticus (young adult females)
Occasional Enterococcus

Urinary Tract Infections

UTI Definition

>105 CFU in symptomatic or catheterize patients

Treat asymptomatic bacteria in pregnant women

Uncomplicated UTI

A UTI in a healthy nonpregnant woman

Complicated UTI

A UTI in anyone else (male, catheter, pregnant female,

pyelo, immunosuppression, structural disease)

Urinary Tract Infections

Antibiotic Coverage

Uncomplicated UTI

Fluoroquinolone (NOT Moxifloxacin)

TMP/SMX
Penicillin (e.g. Amoxicillin)

Complicated UTI

Fluoroquinolone
3rd generation cephalosporin (e.g. Ceftriaxone)
Anti-pseudomonal penicillin (e.g. Pip/Tazo)

MDR organisms what's the big deal?

What are they ESKAPE organisms

Enterococcus

(VRE)
Staph Aureus (MRSA and VISA)
MDR Klebsiella
Acinetobacter
Pseudomonas
Enterobacter sp.

Pseudomonas Coverage options

Antipseudomonal penicillins eg. Pip/Tazo
th
rd
4 generation and one 3 generation
Cephalosporins (eg Cefepime, Ceftazidime)
Carbapenems NOT ertapenam
Ciprofloxacin Not respiratory
flouroquinolones
Monobactams eg Aztreonam
Polymyxins eg. Colistin

Acinetobacter

Follow up sensititivies!
Colistin and Ampicillin/Sulbactam (around 50%
susceptible)

MDR gram negatives

Extended spectrum beta-lactamases (ESBL)

Usually

E. coli and Klebsiella Tx of chioce carbapenems

Inducible Amp C beta-lactamases

SPACE (Serratia, Pseudomonas, Proteus, Acinetobacter, Citrobacter,
Enterobacter) organisms may be reported as suseptible

pip/tazo
Tx of choice 4th generation Ceph or Carbapenem

Klebsiella producing carbapenemases (KPC)

Colistin

to

is treatment of choice

BEWARE! New Delhi metallo-beta lactamases

(NDM-1)
Colistin

is treatement of chioce

Enterococcus Coverage

Enterococcus faecalis and E. faecium

E.

faecalis generally more susceptible and is

frequently covered by aminopenicillins, antipseudomonal PCN, and carbapenems (not
ertapenem)
E. faecium frequently resistant to ampicillin and
more likely to be VRE Daptomycin or Linezolid
treatment of choice

MRSA

HA-MRSA vs. CA-MRSA (distinction blurring)

CA

MRSA usually susceptible to TMX/Sulfa,

Clindamycin, Doxy in addition to Vancomycin
HA MRSA Not usualy susceptible to TMP/Sulfa,
Clinda, or Doxy

Vancomycin, Daptomcyin or Linezolid are treatment options

VISA (Vanco MIC 4-16 microgram/ml)

VRSA (Vanco MIC > 16)

Although

MIC > 2 (and even > 1 in MRSA pneumonia)

may be more likely to lead to treatment failure