ANTIBIOTICS REVIEW 29/4/18, 21)03

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TABLE OF CONTENTS
Master List
ANTIBACTERIALS

Cardiology I. BETA-LACTAMS
II. PROTEIN SYNTHESIS INHIBITORS

Endocrinology III. FLUOROQUINOLONES

IV. SULFONAMIDES = BACTRIM/SEPTRA (TMP/SMX)

Gastroenterology V. "SUPER GRAM POSITIVE ANTIBIOTICS"

VI. "SUPER GRAM NEGATIVE ANTIBIOTICS" THAT COVER PSEUDOMONAS
General Inpatient VII. ANTIBIOTICS WITH ANAEROBE COVERAGE
Medicine
VIII. Urinary Tract Infection-Specfic Antibiotics
IX. ANTI-C.DIFFICILE ANTIBIOTICS
Hematology
X. RIFAMYCINS – include Rifampin, Rifaximin, Rifapentine, Rifabutin.
XI. Last Tidbit: Very common antibiotic regimen = VANCOMYCIN / ZOSYN
Infectious Disease

ANTIFUNGALS
Nephrology
I. AZOLES

Neurology II. ECHINOCANDINS

III. AMPHOTERECIN B

Oncology

Outpatient &
Preventative Medicine ANTIBACTERIALS
I. BETA-LACTAMS = PCNs, Cephalosporins, Carbapenems, Monobactam(Aztreonam)
Palliative Care
Cell wall inhibitors: bind PBPs (Penicillin-binding proteins) in cell membrane and inhibit cell wall crosslinking -
-> bactericidal.
Psychiatry Main side effects: Hypersensitivity reactions including anaphylaxis, Rashes, Bone marrow suppression,
Interstitial Nephritis, GI (nausea, diarrhea, and C.diff) interstitial nephritis, GI (nausea, diarrhea, and C.diff),
Pulmonary/Critical seizures (mainly with high doses in renal failure)
Care As a general rule, if pathogen is susceptible and patient non-allergic, beta-lactams are the preferred drug
for most situations due to high efficacy and cidal nature.
Most oral beta-lactams have poor bioavailability and achieve low serum concentrations, making
Rheumatology them poor choices for serious or deep seated infections (Amoxicillin has the best bioavailability).
No beta-lactam has activity vs MRSA (except Ceftaroline), and none have activity vs atypical intracellular
organisms (i.e. Legionella, Mycoplasma, Chlamydia).
Beta-lactams exhibit time-dependent killing, meaning that efficacy depends on the amount of time the
drug concentration is above the MIC.
The SPICE-A organisms (Serratia, Pseudomonas/Providencia, Indole-positive Proteus, Citrobacter,
Enterobacter, and Acinetobacter) have inducible, chromosomal beta-lactamases (AmpC) that may not be
detected on initial susceptibility testing, but can lead to resistance while on therapy to all beta-lactams
except carbapenems. Cefepime and Piperacillin/Tazobactam can be used with caution as well.

Overview of Beta-Lactam Allergies:

Rash occurs in up to 5% of patients receiving PCN, but the overall rate of anaphylaxis to PCN is
<1/10,000.
Among all patients with reported PCN allergy, ~85-90% will tolerate PCN (either never truly allergic,
or resolution of remote prior allergy).
Clinical cross-reactivity with cephalosporins and carbapenems is very low: of those with a positive
PCN skin test, ~ 2% will have a cephalosporin reaction, and <1% will have a carbapenem reaction.
There is no cross-reactivity between PCN and Aztreonam; however, cross-reactivity between Aztreonam
and Ceftazidime has been reported (due to an identical side chain).
Skin testing is useful to evaluate for potential Type I (IgE-mediated) allergic reaction (only 10-15% of those
with reported allergy will have positive skin test). Skin test has ~50% positive predictive value à give
alternate drug, do graded challenge, or desensitize. Skin test has very a high negative predictive
value: >98% will tolerate PCN, but not 100% à give 10% “test” dose and observe for 1 hour prior

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to full dose.
If skin testing unavailable and beta-lactam is preferred, decision depends on prior type of reaction and how
recently it occurred. If >10 years ago, and/or not characteristic of IgE, give cephalosporin or carbapenem
(<1% of anaphylaxis). If recent and/or features of IgE reaction, can give cephalosporin or carbapenem by
graded challenge. If probable history of anaphylaxis, desensitize.

A. PENICILLINS

1. Penicillin G (IV) or V (PO)

Spectrum: Many strains of Streptococci (Drug of choice for Group A Strep - universally PCN
sensitive), minority of Staphylococci (most are resistant) and some Enterococcus, most oral anaerobes,
Syphilis (universally PCN sensitive).

Used for: Strep throat and other infections due to Group A Strep, Syphilis (for neurosyphilis or pregnant
women, must desensitize to PCN), bacteremia/endocarditis due to PCN sensitive Streptococcus,
Enterococcus, or Staph aureus (<10% of S.aureus strains are PCN-sensitive), and more. For most
situations, generally start with broader antibiotics until pathogen and susceptibilities identified.

2. Aminopenicillins - Ampicillin (IV), Amoxicillin (PO)

Spectrum: some Gram positives (Strep, Enterococcus, Listeria) but NOT MSSA, and limited Gram
negative coverage. Notable gram negative holes include Klebsiella, Moraxella, and SPICE A organisms.
Used for: Upper respiratory infections, sinusitis, otitis media, cellulitis, Listeria infections, UTI’s, early
Lyme disease (alternative to Doxycycline), and more.
Drug of choice for Enterococcal infections if susceptible (E.faecalis generally susceptible,
E.faecium usually not). Used with aminoglycosides for synergy for Enterococcal endocarditis.
Amoxicillin is the best-absorbed beta lactam (75-90% bioavailability). Little role for oral
ampicillin due to inferior absorption vs Amoxicillin.

3. Anti-Staphylococcal Penicillins - Methicillin / Nafcillin / Oxacillin (IV), Dicloxacillin (PO)

Spectrum: MSSA, also with activity vs strep.
Used for: Drug of choice for MSSA infections (unless PCN sensitive, which is rare). Good choice for
cellulitis, osteomyelitis, endocarditis, and bacteremia from MSSA.
No MRSA coverage and Coag negative Staph is usually resistant (>80%).
Dicloxacillin is a reasonable oral choice for non-severe cellulitis; otherwise, for all serious
MSSA infections (e.g. bacteremia, osteomyelitis, endocarditis), in general the entire
course of therapy must be given intravenously.
Nafcillin tends to be better tolerated than Oxacillin (less hepatitis and rash)

4. Anti-pseudomonal PCNs - Piperacillin, Ticarcillin

Usually combined with beta lactamase inhibitors (see below) which confers broader activity; however,
beta-lactamase component does not add activity vs Pseudomonas (so if Pseudomonas is sensitive, could
use Piperacillin alone).

B. COMBINED PENICILLIN/BETA-LACTAMASE INHIBITORS:addition of beta lactamase inhibitor confers broader

spectrum against common beta-lactamase producing organisms (such as MSSA, some gram negatives including
H.influenza, Moraxella, and virtually all anaerobes).

Amoxicillin/Clavulanate (Augmentin) – PO

Spectrum: Relatively broad spectrum with some gram positive (MSSA, Strep), some gram negatives, and
anaerobes. Notable holes include NO Pseudomonal activity and other SPICE A organisms.
Used for: Sinusitis, respiratory infections, otitis media, some skin/soft tissue infections (including bite
wounds), and more.

Ampicillin/Sulbactam (Unasyn) – IV

Spectrum: Similar to Amoxicillin/Clavulanate, except has activity vs most Acinetobacter (sulbactam

component has activity). Still no activity against other SPICE organisms.
Used for: similar situations as for Amoxicillin/Clavulanate but where IV form is desirable; also, some
intraabdominal and GYN infections, aspiration pneumonia and lung abscesses, and more.
Caution with Unasyn for polymicrobial intraabdominal infections due to high rate of
resistance of E.coli (>50% at some institutions)

Piperacillin/Tazobactam (Zosyn) – IV

Spectrum: similar to Unasyn in having gram positive, gram negative, anaerobic coverage, but better
overall gram negative coverage, including Pseudomonas and most SPICE A organisms.
Used for: many purposes, including hospital-acquired/healthcare-associated PNA, severe skin/soft tissue
infections including diabetic ulcers, intraabdominal infections.
Very broad antibiotics so easier to remember common bugs that it does NOT cover:
MRSA, most strains of VRE, many Coag negative staph strains, Atypicals (Chlamydia,
Mycoplasma, Legionella), ESBLs.

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Note Zosyn’s higher dosing for PNA/Pseudomonas coverage: 4.5 g q6 hrs (vs. 3.375 g q6 for
other indications)
“Extended Infusion” strategy – 3.375 g over 4 hours, q8 hrs – some data suggesting better
outcomes for treatment of Pseudomonas infections compared to standard dosing (goal to
maximize time above MIC).

Ticarcillin/Clavulanate (Timentin) – IV

Similar to Zosyn, but Timentin has activity vs Stenotrophomonas, and is less effective
vs Pseudomonas and Enterococci.

C. CEPHALOSPORINS - higher resistance to beta-lactamases à better anti-staph activity

Spectrum (General Rules):
No cephalosporin covers Enterococcus (except Ceftaroline).
Only Ceftazidime and Cefepime cover Pseudomonas.
Only Cefoxitin and Cefotetan have good anaerobic coverage.

1st Generation - Cefazolin (Ancef, Kefzol) - IV, Cephalexin (Keflex) - PO

Spectrum: Excellent Gram positive (MSSA and strep), minor Gram negative = Proteus,
E.coli, Klebsiella.
Used for: Mild-moderate nonpurulent cellulitis (if do not suspect MRSA). Cefazolin ofted
used for prophlaxis during surgery. Sometimes used for UTIs as well (especially during
pregnancy).

In PCN-allergic patients, Cefazolin is drug of choice for severe MSSA infections

(bacteremia, endocarditis, etc). Some use it preferentially in prolonged treatment courses over
Nafcillin/Oxacillin due to overall better tolerance (less rash, diarrhea, interstitial nephritis,
hepatitis)

2nd Generation
Cefuroxime (PO and IV)

Spectrum: Gram positive and more gram negative’s than 1st generation - gains activity vs H.influenza,
Enterobacter, Neisseria.
Used for: respiratory infections (upper and lower tract), gonorrhea, UTIs, Lyme disease (alternative to
Doxycycline), and more.

”Cephamycins” - Cefoxitin, Cefotetan (IV)

Spectrum: get anaerobes and gram negatives, but no Pseudomonas and weak/unreliable gram
positive coverage.
Used for: UTI’s, non-severe intraabdominal infections, pelvic/GYN infections.
Bacteroides fragilis has high rates of resistance to Cefotetan (Cefoxitin is a bit
better) – for serious intrabdominal infections, should use other agents.
Cefotetan can cause elevated INR.

3rd Generation

a. Ceftriaxone (Rocephin) – IV, Cefotaxime - IV, Cefpodoxime - PO

Spectrum: Good gram positive (although possibly worse than 1st generation) and excellent
gram negative coverage (E.coli, Proteus, Klebsiella, Neisseria, H.influenza, and most SPACE
organisms, but not Pseudomonas), no anaerobes .
Used for: Ceftriaxone used in many situations including community acquired PNA (with
Azithromycin), meningitis (CTX has excellent CSF penetration), spontaneous bacterial
peritonitis, some skin/soft tissue infections, bacteremia/endocarditis from susceptible strep,
urinary tract infections/pyelonephritis, bone and joint infections, late Lyme disease,
gonorrhea, pelvic infections, and more.

Note small but important rate of resistance in Strep pneumo.

Ceftriaxone usually once daily dosing (1-2 g) except for meningitis (2 g IV q12 hours).
Cefotaxime is more frequent dosing (often used preferentially for spontaneous bacterial
peritonitis due to good track record and high levels achieved in ascitic fluid, but Ceftriaxone
probably equivalent).
Cefpodoxime useful as a step-down to oral after IV Ceftriaxone, but like all beta lactams note
poor serum bioavailability (so not suitable for bacteremia, deep-seated or serious infections).
Ceftriaxone can cause biliary sludging and cholecystitis.

b. Ceftazidime (IV) (3rd/4th Generation Cephalosporin)

Spectrum: only has Gram negative coverage (including Pseudomonas). Virtually no Gram
positive or anaerobic coverage.

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Used for: Pseudomonal infections, also can be used for neutropenic fever (but beware lack of
staph/strep coverage, so Cefepime often preferred).
Most experts will avoid using Ceftriaxone or Ceftazidime (and any lower generation
cephalosporin) for serious infections due to SPICE organisms, due to concern for
inducible resistance from chromosomal beta-lactamase (AmpC ). Preferable to use
Cefepime, Piperacillin/Tazobactam, or Carbapenem (best) in those situations as they are more
stable, or non-beta lactams if susceptible.

4th Generation - Cefepime (IV)

Spectrum: broad gram positive (MSSA, strep) and gram negative including Pseudomonas, but weak
anaerobic coverage.
Used for: empiric neutropenic fever (better than Ceftazidime due to strep coverage), hospital acquired
PNA, meningitis if suspect gram negatives, complicated urinary tract infections, nosocomial meningitis,
and more.
For cefepime and ceftriaxone, beware CNS toxicity of encephalopathy, altered mental status, and
seizures in the elderly and those with renal failure.
Ceftazidime and Cefepime sometimes have activity against certain ESBL producing
organisms, but reports of failure in this setting so use with caution.
Ceftazidime and Cefepime have <1% cross-reactivity for non-anaphylactic allergies/intolerance

5th Generation - Ceftaroline (IV)

Spectrum: Gram positive including MRSA, VISA, VRSA, Strep. Similar gram negative coverage as
Ceftriaxone – no Pseudomonas and other nonlactose fermenting GNRs, no ESBL. No entercoccus as
monotherapy, though some evidence to support synergy with other drugs (e.g. dapto)
Used for: complicated SSTI and community-acquired PNA (FDA indications)
Newest cephalosporin (FDA approved in 2010) and only one with activity vs MRSA.
Only 2 FDA approved indications, but being used more and more for off-label purposes
(bone/joint infections, refractory MRSA/VISA bacteremia, etc.).

D. CARBAPENEMS - Imipenem/Cilastin, Meropenem, Ertapenem, Doripenem (all IV)

Spectrum: Broadest spectrum antibiotics, cover Gram positive, Gram negative including Pseudomonas
(except Ertapenem) and ESBL (extended spectrum beta lactamase producers), also anaerobes.
Used for: many serious infections due to resistant gram negatives, including hospital/health-care
associated PNA, meningitis, intraabdominal infections, complicated skin and soft tissue infections
The most reliable class of antibiotics against ESBL organisms and the SPICE-A organisms.
Very broad – easier to remember common bugs that it doesn’t cover: MRSA, most VRE,
Atypicals, Stenotrophomonas (carbapenem use is a risk factor for Stenotrophomonas infection).
Great penetration virtually everywhere, including CSF .
Ertapenem does NOT cover Pseudomonas, but does still cover ESBL (main advantage is
convenient once/day dosing - great outpatient IV drug). Other differences of Ertapenem (vs
other carbapenems) is lack of activity vs Acinetobacter and Enterococci.
Doripenem – newest carbapenem, main theoretical advantage = increased in vitro potency
against Pseudomonas, and lower likelihood of development of resistance in vitro (clinical benefit
not yet demonstrated)
Main additional side effect = Lower seizure threshold – greatest risk w/ Imipenem (esp with
renal failure), less w/ Meropenem.

E. MONOBACTAM - Aztreonam

Spectrum: only has activity vs. aerobic gram negatives, no gram positive or anaerobes (similar activity
as Ceftazidime).
Used for: hospital acquired/healthcare associated PNA, UTIs, intraabdominal infections, sepsis, skin and
soft tissue infections. Generally used in combination with other antibiotics due to gram-negative limited
spectrum.
Main advantages:1) No cross-reactivity with PCN allergy (except with Ceftazidime –
cross-reactivity due to identical side chain) and 2) Does not cause renal failure (almost no
significant toxicity)
Beware significant rate of resistance of Pseudomonas in most institutions, so empiric
double coverage often required.

Comparison of the 3 broadest spectrum beta-lactams: Cefepime, Zosyn, and Carbapenems

(non-Ertapenem) have activity against both Gram positive (MSSA, Strep) and Gram negative
including Pseudomonas. They do NOT cover: MRSA, VRE, Atypicals, among others.
Cefepime – main weakness is weak anaerobe coverage and no Enterococcus
Zosyn (Piperacillin/Tazobactam) – broader due to excellent anaerobe coverage, activity vs Amp-
susceptible Enterococcus. No ESBL coverage.
Carbapenems (except Ertapenem) – broadest yet due to anaerobic coverage, Amp-susceptible
Enterococcus, and ESBL

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II. PROTEIN SYNTHESIS INHIBITORS

Mechanism: bind to either 30 S or 50 S ribosomal unit. Most are bacteriostatic, except for
Aminoglycosides (generally considered cidal due to irreversible binding and disruption of outer cell
membrane)

1. Macrolides - Erythromycin, Clarithromycin, Azithromycin -50S Ribosomal Inhibitor (PO and IV)
Spectrum: Atypical organisms (Chlamydia, Mycoplasma, Legionella), also some activity vs. Gram positive
cocci and some gram negatives.
Used for: Azithromycin - low-risk bronchitis, COPD exacerbations, community-acquired pneumonia,
sinusitis, Strep throat in PCN allergic patients, and more. Used in conjunction with Ceftriaxone for CAP
that requires hospitalization. Used for MAC treatment (combination therapy) and for prophylaxis in
HIV/AIDS patients with CD4 <50. Also used for STD Chlamydia.
Azithromycin is the drug of choice for most atypical infections.
Erythromycin now used mostly as GI motility agent – prior to endoscopy, or to advance feeding
tubes.
Clarithromycin also used for MAC treatment (in combination with other drugs).
Azithromycin has better H.influenza activity than Clarithromycin/Erythromycin.
~25% of Strep pneumo is resistant to Azithromycin, so combine with Ceftriaxone for
patients sick enough to hospitalize with community-acquired PNA (or recent abx use).
Side effects: QT prolongation (recent NEJM article suggested slight increased risk of
cardiovascular death with Azithromycin), prominent GI side effects, rash.

2. Tetracyclines – Doxycycline, Tetracycline, Minocycline - 30S Inhibitors (PO and IV)

Spectrum: Fairly broad spectrum with some Staph and MRSA coverage, some gram negative coverage,
and atypicals. Has activity for unusual pathogens including: Rickettsia, Lyme disease,
Tularemia, Vibrio, Brucella, Q fever, Anthrax
Used for: Doxycycline - Skin and soft tissue infections when suspect community-acquired MRSA,
respiratory tract infections, and unusual infections as above. Drug of choice for early Lyme disease, and
for Lyme prophylaxis after tick bite. Also used for malaria prophylaxis, acne and rosacea.
Side Effects: photosensitivity, GI discomfort, teeth discoloration, inhibits bone growth in children,
teratogenic, steatosis and hepatotoxicity.
Doxycycline is the preferred tetracycline in most cases due to convenient BID dosing, and
lack of food-drug interactions.
Often part of empiric therapy in toxic-appearing patients with fever and rash (mainly for Rocky
Mountain Spotted Fever).
Good choice for mild-moderate skin/soft tissue infections due to community-acquired
MRSA infection, but has poor strep coverage so often combined with beta lactam like
Cephalexin.
Doxycycline has excellent bioavailability .

3. Clindamycin -50 S inhibitor (PO and IV)

Spectrum: Excellent activity vs. Anaerobes and Gram positive cocci – Strep and Staph, including ~
50% of community-acquired MRSA, but NOT Enterococci.
Used for: skin/soft tissue infections, pelvic infections, lung abscess, sinusitis. Also has activity vs PCP
(combine with primaquine) and toxoplasmosis (combine with pyrimethamine)
Beware increasing resistance among Bacteroides – not a good choice for severe intraabdominal
infections.
Reasonable empiric drug for cellulitis due to Strep/Staph coverage, but beware of
resistant MRSA. Also, ~10% of MSSA is resistant.
If MRSA (or MSSA) appears susceptible – always have lab check “D-test” à looks for
inducible resistance to Clindamycin in strains that are resistant to Erythromycin. If D-test
positive, do not use Clindamycin.
Also used often for its Antitoxin effect in Toxic Shock Syndrome or Necrotizing Fasciitis
due to Group A Strep (less evidence for MRSA).
Does not penetrate CSF – cannot use for brain abscesses.
Traditionally causes highest rate of C.diff among all Abxs (~10%).

4. Aminoglycosides - Gentamicin, Tobramycin, Amikacin, Streptomycin -30S inhibitor (all IV)

Spectrum: Extremely efficacious vs. aerobic Gram negatives including Pseudomonas. NO activity
vs. Gram positives (except when used for synergy) or anaerobes.
Used for: serious gram negative infections especially when Pseudomonas is suspected (pneumonia,
bacteremia, urinary tract infections). Used with beta-lactams against gram positive organisms for
synergistic effect (mainly in endocarditis).
For synergy, best evidence and utility for Enterococcal endocarditis (if susceptible). Also
strong recommendation for Strep enterocarditis (duration depends on Strep MIC).
Weakest evidence for Staph aureus native valve endocarditis – optional for max 3-5 days
(decreases bacteremia by ~1 day, increases renal failure, and no effect on mortality) à most ID
physicians now tend to avoid it for Staph infections. For Staph prosthetic valve
endocarditis, aminoglycoside recommended for 2 weeks with Rifampin.

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Poor urine and CSF penetration. Also less effective at low pH such as in lung/bronchial
secretions – not great for PNA (avoid monotherapy).
Ofted used as 2nd agent of “double coverage” when suspecting serious Pseudomonas infection
(including for HAP/HCAP/VAP)
Side effects = ATN/nephrotoxicity (manifests after 3-5 days, usually reversible) and
oto/vestibular toxicity (irreversible, unlike Vancomycin). If using long-term, check baseline
audiology test and ~q2 weeks.
Aminoglycosides exhibit concentration-dependent killing – more effective with higher peak
concentration relative to MIC (vs time-dependent killing of beta lactams – more important to
maintain levels above MIC)
Three ways to dose aminoglycosides (doses listed for Gentamicin). Check peak after 3rd dose,
trough before 4th dose.
Traditional q8 dosing (~2 mg/kg q8 hrs) – goal peak >6-8 and trough <2
Once-daily dosing (5-7 mg/kg) – generally do not measure troughs unless critically ill and high
risk of toxicity (goal trough <1). Avoid if unstable renal function/renal failure or increased
volume of distribution. Once daily dosing takes advantage of concentration-dependent killing
and long “post-antibiotic effect” (killing/inhibition of bacteria even when abx is cleared) – other
potential advantage is lower toxicity.
Synergy dosing (~1 mg/kg q8-12 hrs) – goal peak 3-5, trough <1.

5. Chloramphenicol – 50S ribosomal inhibitor. IV or PO (but PO form unavailable in U.S.)

Spectrum: Broad spectrum vs Gram positives (including MRSA, E.faecium/VRE); Gram negatives but NOT
Pseudomonas; Anaerobes, and unusual pathogens including spirochetes, Rickettsia, Erhlichia, Coxiella,
Typhoid/Paratyphoid Salmonella.
Used for: Limited use in the U.S. due to potential toxicity (see below) – mainly for bacterial meningitis
in patients with severe beta-lactam allergy (has activity vs S.pneumo, N.meningitidis, and
H.influenza). Used more widely in developing countries where benefit often outweighs risk.
A typical regimen in patients with bacterial meningitis and severe beta-lactam allergy
would be Vancomycin + Chloramphenicol +/- Bactrim (for Listeria in the appropriate
patients)
Toxicity: 1. Bone marrow suppression – direct, dose-related effect that is reversible. 2. Aplastic
anemia – rare, idiosyncratic reaction (occurs at rate of 1/40,000), but generally fatal event.
Usually occurs several weeks after drug is stopped. 3. Gray baby syndrome in infants – presents
with hypotension, shock, and cyanosis.

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III. FLUOROQUINOLONES = DNA Gyrase and Topoisomerase inhibitors àbactericidal

Mechanism: DNA Gyrase and Topoisomerase inhibitors àbactericidal

Side effects: QT prolongation (recent NEJM article suggested increased risk of cardiovascular death with
Levofloxacin, but not Ciprofloxacin), tendon rupture (esp if on steroids), GI intolerance, cartilage damage,
rare dysglycemias (Gatifloxacin removed from market for this reason), dizziness/HA’s, rashes,
teratogenicity, transaminitis. Fluoroquinolones also recently associated with increased risk of retinal
detachment. High rate of c.diff.
Fluoroquinolones also have excellent TB coverage (Moxifloxacin > Levofloxacin >
Ciprofloxacin). If patient has PNA, but suspect TB, do not use FQ’s!!(Do not want to use
monotherapy against TB à will develop resistance)
All fluoroquinolones have atypical coverage (but Cipro – relatively weaker against Chlamydia and
Mycoplasma, but good vs Legionella).
All fluoroquinolones have excellent bioavailability (except Norfloxacin), so use PO
whenever possible.

1. Ciprofloxacin (PO and IV)

Spectrum: best gram negative coverage of FQs, but virtually no gram positive coverage. Lacks
good anaerobic coverage.
Used for: many purposes including UTIs, double coverage of Pseudomonas including for HAP/HCAP/VAP,
bone and joint infections, prostatitis, GI/intraabdominal coverage - often with Flagyl, traveler’s diarrhea.
Also effective vs anthrax.
Common myth is that it does not “penetrate” the lungs. This is false – it is not used in
community-acquired PNA due to lack of Strep pneumo coverage. It is routinely used
for HAP/HCAP/VAP as double-coverage for Pseudomonas (note more frequent dosing for
PNA – 400 mg IV q8 hours)

2. Levofloxacin (Levaquin)(PO and IV)

Spectrum: “Respiratory Fluoroquinolone” - excellent activity vs. Strep pneumo, slightly less reliable
Pseudomonas coverage than Cipro. Good for atypicals.
Used for: Community Acquired PNA (can use as monotherapy), sinusitis/bronchitis, UTI’s, and
double coverage of Pseudomonas including hospital acquired PNA.

3. Moxifloxacin (Avelox) (PO and IV)

Also a Respiratory FQ, but main difference vs. Levofloxacin is virtually NO urine activity (can't
use for UTIs) and NO Pseudomonas activity à no role in hospital/healthcare associated

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PNA.
Best gram positive, atypical, and anaerobic coverage out of FQs à approved for complicated
intraabdominal infections, although significant rate of resistance in Bacteroides (either avoid for
serious intraabdominal infections, or combine with Metronidazole).
Both Moxifloxacin and Levofloxacin are not typically used for Staph aureus infections
due to rapid emergence of resistance.
Both Moxifloxacin and Levofloxacin have excellent Pneumococcal activity, but are 2nd-
line at best for most other streptococcal infections (beta-lactams preferred).
Norfloxacin (PO) – unlike the other Fluoroquinolones, poorly absorbed. Main use is for
spontaneous bacterial peritonitis (SBP) prophylaxis.

IV. SULFONAMIDES = BACTRIM/SEPTRA (TMP/SMX) - inhibit sequential steps in Folate synthesis -->
bacteriostatic

Spectrum: Wide spectrum including typical bacterial pathogens – Gram positives (S.aureus including most
CA-MRSA, some S.pneumo), and most Gram negatives but not Pseudomonas. Notable highlights that set
it apart from other agents are: activity vs Pneumocystis jiroveci, Nocardia, Toxoplasmosis,
Listeria, Isospora, and Stenotrophomonas.
Used for: Many purposes including PCP PNA (drug of choice, both for treatment and prophylaxis),
Community-acquired MRSA Skin infections, UTIs, Nocardiosis, Listeria infections in PCN-allergic patients,
Salmonella infections, Traveler’s diarrhea, acute bronchitis, and otitis media.
Good choice for skin/soft tissue infections due to MRSA coverage (best CA-MRSA
coverage out of oral Abxs except for Linezolid), but weak strep coverage à consider
adding Cephalexin for strep.
~100% PO bioavailability. Shortage of IV formulation in the U.S. so use PO whenever possible.
Dosing – SS = 400 mg (SMX) /80 mg (TMP), DS – 800/160 mg. Dosing varies on indication.
Selected few: UTI – 1 DS tab po bid. SSTI – 2 DS tab po bid. PCP ppx – 1 DS tab po three
times/week or qday, or 1 SS tab po qday. PCP treatment – 5 mg/kg (TMP component) PO q8
hours x 21 days (usually 2 DS po q8 hours).
Many potential side effects:
Common - Hypersensitivity (sulfas) and rashes, GI side effects, dose-dependent bone marrow
suppression, increased creatinine (both from pseudo-Cr elevation due to blocked Cr
secretion into tubules – average increase in Cr by ~20%, and true AKI from Interstitial
Nephritis and ATN), hyperkalemia (esp high doses and with CKD)
Uncommon - aseptic meningitis, methemoglobinemia and hemolysis in G6PD deficiency,
transaminitis/cholestasis, pancreatitis, and more.

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V. “SUPER GRAM POSITIVE ANTIBIOTICS”

Included are drugs with activity against MRSA, Coag-negative staph, Streptococci, Enterococcus including
VRE (except Vancomycin)

1. Vancomycin (IV), dalbavancin (IV); (lipoglycopeptide antibiotics)

Mechanism: Glycopeptide - inhibits cell wall synthesis in Gram positives (different protein than beta
lactams – D-Ala-D-Ala).

Spectrum: gram positive agent with activity vs Staph (including MRSA), Strep, and nonVRE Enterococcus.
No gram negative coverage. Considered the gold standard for MRSA infections.
Used for: all sorts of situations with suspected or proven gram positive infections from above organisms,
including bacteremia, meningitis, PNA, skin/soft tissue, and more. Drug of choice for gram positive
infections in patients with severe beta-lactam allergy.
Considered a slowly cidal drug (compared to beta-lactams), but static vs Enterococcus
Not as effective as Nafcillin against MSSA, due to slowly cidal nature à increased treatment
failure/relapse when used for MSSA bacteremia/endocarditis!
VISA = MIC 4-8, VRSA = MIC ≥16. Avoid for MRSA infections with MIC ≥2 à increased
treatment failure
PO form is not absorbed – used for severe C.diff infections (superior to Metronidazole)
Side effects: Red man syndrome (due to histamine release àcan lessen by slowing the infusion
rate and pretreatment with antihistamines), nephrotoxicity (ATN), and ototoxicity (reversible, as
compared to aminoglycosides), bone marrow suppression (leukopenia > thrombocytopenia)
Dosing – typical = 15 -20 mg/kg (actual body weight) q12 hrs, can load 25-30 mg/kg in critically
ill patients. The typical 1 g q12 dosing is inadequate for most patients. For severe renal
failure, can dose “by levels” – i.e. load 15 mg/kg, then check daily levels and redose when level
<10-15.
Check trough prior to 4th dose for severe infections or those with unstable renal function. Goal
trough 15-20 for severe/invasive MRSA infections (~20 for CNS infections), 10-15 for
less severe infections (i.e. routine cellulitis, coag negative staph, etc.). Some experts will not
even check troughs in non-severe, non-MRSA infections in patients with stable renal

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function.

Dalbavancin (IV) - newer 2nd generation lipoglycopeptide antibiotic, with similar spectrum of vancomycin
and indicated for skin and soft tissue infection. Main advantage is once a week dosing (injected at depot
that slowly releases).

2. Linezolid (Zyvox) (PO and IV)

Mechanism: Oxazolidinone class –unique ribosomal inhibitor (acts on 50S subunit). Bacteriostatic agent.
Spectrum: covers all Gram positives including strep, MRSA and VRE. Also has good activity vs
tuberculosis.
Used for: skin/soft titssue infections, HAP/HCAP/VAP with suspected MRSA, VRE infections
Oral form has virtually 100% bioavailability
Controversial: may be superior for MRSA pneumonia than Vancomycin à better lung
penetration and antitoxin effect? Also: may be superior vs Vancomycin for complicated
skin/soft tissue infections due to MRSA – similar rationale (tissue penetration, antitoxin
effect)
Side effects: Expensive! Also: Bone marrow suppression especially thrombocytopenia
(reports of reversal with pyroxidine) - ~5% rate after several weeks, increased risk with renal
failure. If using for >1 week, monitor CBC closely. Also, Linezolid is a MAO inhibitor – risk of
serotonin syndrome with SSRI’s, avoid co-administration. Long term usage can lead to
mitochondrial toxicity à lactic acidosis, peripheral neuropathy, optic neuritis and blindness. In
general, Linezolid is well tolerated for short-term, but not so much long-term.
Since mechanism is static, in general prefer other agents for severe bacteremia, endocarditis.

3. Daptomycin (IV)
Mechanism: Lipopeptide antibiotic – forms transmembrane channels and depolarizes cells. Rapidly cidal
drug.
Spectrum: only covers Gram positives including MRSA, strep, and Enterococcus/VRE. No gram negative
activity.
Used for: complicated skin/soft tissue infections, also being used more for MRSA bacteremia/endocarditis
(due to cidal nature)
Cannot use for pneumonia (lacks activity in lung parenchyma due to inactivation by
surfactant)
Achieves high serum levels, but poor penetration into CNS, bone
Main side effect = muscle toxicity (myalgias, rhabdomyolysis) àcheck baseline and
weekly CK, and discontinue statins. Also: peripheral neuropathy, GI side effects, pain at
injection site
Dosing depends on indication – 6 mg/kg (or higher - 8-10 mg/kg) qday for
bacteremia/endocarditis, 4-6 mg/kg qday for skin/soft tissue infections.
Resistance commonly emerges when used long-term for MRSA and VRE infections.
Also, rise in Vancomycin MIC parallels emergence of Daptomycin resistance (if
Vancomycin MIC ≥2, be sure to check for Daptomycin resistance).

4. Synercid (Quinupristin/Dalfopristin) (IV)

Mechanism: “Streptogramins”– inhibits sequential steps in ribosomal synthesis
Spectrum: covers MRSA and VRE due to E.faecium. Does not cover E.faecalis (has natural efflux pump).
Used for:Not much, as it is very poorly tolerated due to thrombophlebitis at IV siteà generally need
central line. Also severe myalgis/arthralgias and lots of drug-drug interactions (CYP450 inhibitor). Poor
choice for bacteremia/endocarditis due to static nature.

5. Tigecycline(IV)
Mechanism: Glycylcycline class - structurally related to Tetracyclines (bacteriostatic). Only IV.
Spectrum: Broad coverage - Gram positive (including MRSA and VRE), Gram negatives, anaerobes, and
atypicals. Notable holes in coverage include Pseudomonas, Proteus, and Providencia.
Used for: complicated intraabdominal infections, skin/soft tissue infections, and sometimes for
pneumonia.
Beware overall increased risk of death when used for severe infections (2010 metanalysis) –
FDA black box warning!
High rate of failure for HAP/VAP, use with caution
Achieves low serum concentrations (distributes widely into tissues) – poor choice for
bacteremia (also note its static mechanism)
Sometimes effective against MDR gram negative pathogens including some ESBL and
carbapenemase-producing strains – if dealing with such a bug, should ask micro to test
susceptibility to tigecycline.
Main side effects = GI (nausea/vomiting/diarrhea) and elevated LFTs

6. Ceftaroline (5th Gen Cephalosporin) – see Beta-lactam section above. Covers MRSA, VISA, VRSA,
Strep, Enterococcus faecalis/VRE (but not as good vs E.faecium). Similar gram negative coverage as
Ceftriaxone.

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VI. “SUPER GRAM NEGATIVE ANTIBIOTICS” THAT COVER

PSEUDOMONAS
Pseudomonas aeruginosa is a non-fermenting Gram-negative bacillus that inhabits a variety of
environments (soil, water) and causes nosocomial infections (HAP/VAP, catheter-related infections, UTIs,
post-surgical) and commonly affects immunocompromised patients (common cause of neutropenic fever,
ecthyma gangrenosum), cystic fibrosis, and burn patients. It is feared due both for its inherent resistance
to most antibiotics as well as its propensity to develop resistance.
For serious infections due to suspected Pseudomonas, generally recommended to
“empirically double cover” with two antibiotics from different classes until
susceptibilities identified, then narrow appropriately to one drug. However, the utility of
“continued double-coverage” (after susceptibilities identified) is a long-standing point of
controversy – some experts recommend this for serious infections including bacteremia
in neutropenic patients, endocarditis, meningitis, and possibly pneumonia.
Double coverage involves a beta-lactam plus either Fluoroquinolone or Aminoglycoside. Use
Aztreonam if PCN-allergic. Avoid double beta-lactam therapy.
Only Ciprofloxacin and Levofloxacin come in PO form, all other are IV only.

1. Zosyn(Piperacillin/Tazobactam) and Timentin (Ticarcillin/Clavulanate) – note high rates of resistance

to Ticarcillin.
2. Carbapenems – Meropenem, Imipenem , Doripenem. Remember: Ertapenem has no activity.
3. Ceftazidime, Cefepime (4th gen cephalosporin)
4. Aztreonam – high rates of resistance at most institutions, so use only if PCN-allergic, and
empirically double-cover.
5. Fluoroquinolones - Ciprofloxacin (~70% coverage) > Levofloxacin (~65%), NOT Moxifloxacin
(0%) - usually used as double coverage, not for monotherapy for empiric Pseudomonas treatment.
6. Aminoglycosides – On average, Amikacin > Tobramycin > Gentamicin - generally do not use
as monotherapy for serious Pseudomonas infections except for UTIs (tend to have worse
outcomes), only as 2nd agent added to primary beta lactam therapy.

7. Polymyxins - Colistin (Polymyxin E) and Polymyxin B(IV)

Mechanism: cationic detergent – binds to (and disrupts) lipids of bacterial cell membranes. Cidal
mechanism.
Spectrum: Active mainly against Gram negative organisms including Pseudomonas, Klebsiella,
Enterobacter, Acinetobacter. No activity vs Gram positives. Limited activity vs anaerobes. Proteus and
Serratia are generally resistant.
Used for: generally reserved for multidrug-resistant gram negative infections from above organisms,
including pneumonia, bacteremia, and others.
Can be given in aerosolized form as well as IV (both forms used quite commonly in Cystic
Fibrosis patients with resistant gram negative infections)
Old drugs that had been long abandoned for routine use due to its toxicity à Nephrotoxicity
(reversible, dose-dependent) and Neurotoxicity (dizziness, pareshtesias, vertigo,
ataxia, etc), but recently experiencing a comeback due to rise in resistant gram negatives.
May be better tolerated than older literature suggests.

*Treatment of HCAP/HAP/VAP in patients with high risk of MDR organisms: Essential to

empirically treat for MRSA, and Gram negatives including Pseudomonas *
Empiric 2-3 Drug Regimen:
Anti-MRSA Antibiotic: Vancomycin or Linezolid (Not Daptomycin)
Anti-Pseudomonal Beta-lactam Antibiotic: Ceftaz/Cefepime, Piperacillin-Tazobactam,
Carbapenem (not Ertapenem), or Aztreonam
“Double Coverage” Agent for Pseudomonas (Optional – depending on severity of illness,
local antibiotic susceptibility patterns, etc): Aminoglycoside, or Ciprofloxacin/Levofloxacin (Not
Moxifloxacin). FQ’s have additional advantage of atypical coverage in cases where this is a
possibility.

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VII. ANTIBIOTICS WITH ANAEROBE COVERAGE

Infections in which anaerobes are likely to play an important role include (from head to toe):
CNS abscesses (Brain, epidural, subdural)
Infections arising from the oral cavity (Dental abscesses, Peritonsillar abscess, Deep neck space
infections) – major pathogens include Peptostreptococcus, microaerophilic streptococci,
Fusobacterium, and others.
Aspiration pneumonia/lung abscesses/empyema – same pathogens as oral infections
Intraabdominal infections (e.g. perforation, peritonitis, intraabdominal abscesses) – major
anaerobic pathogen is Bacteroides species
Gynecological infections (endometritis, tuboovarian abscesses, pelvic inflammatory disease)–
major pathogens include Prevotella species and others
Certain skin and soft tissue infections (Fournier’s gangrene, diabetic foot ulcer, decubitus ulcers,
bite wounds) – anaerobic pathogens depend on site.

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For intraabdominal infections, avoid Clindamycin, Moxifloxacin, and Cefotetan/Cefoxitin due to

increasing resistance amongst Bacteroides. Apart from these drugs, all antibiotics listed below have
excellent Bacteroides coverage and as a general rule, do not need to “double cover” anaerobes.

1. Metronidazole (Flagyl)(PO and IV)

Mechanism: selectively taken up by anaerobic bacteria and reduced by proteins in the electron transport
chain, leading to DNA disruption.
Spectrum: Anaerobes (including C.difficile), and Protozoans: Giardia, Trichomonas, Entameba histolytica,
also Helicobacter pylori (part of triple therapy).
Used for: Anaerobic infections usually in conjunction with other agents (since anaerobes usually part of a
polymicrobial infection). Also used for mild-moderate C.diff , and protozoal infections as above.
Drug of choice for most anaerobes, but with notable lack of activity against
Propionibacterium acnes, Actinomyces, and Lactobacillus.
Classically best for infections “below the diaphragm” – mainly due to excellent activity vs
Bacteroides, and less reliable activity vs Peptostreptococcus (gram positive oral anaerobe) and
total lack of activity vs microaerophilic streptococci. For this reason, should never use
as monotherapy against above-the-diaphragm infections like lung abscesses, etc. (but
fine to combine with beta-lactam, levofloxacin, etc).
Excellent (virtually 100%) bioavailability
Good CSF penetration (unlike Clindamycin).
Side effects: nausea, diarrhea, metallic taste, dose-dependent and possibly cumulative
peripheral neuropathy (avoid multiple courses for recurrent C.diff), also Disulfiram effect w/
EtOH. Peripheral neuropathy is usually reversible. Not well tolerated long-term.

2. Clindamycin – classically for infections above the diaphragm, as it also has activity vs microaerophilic
streptococci; avoid in intraabdominal infections due high rates of resistance among Bacteroides
species (up to 40% or more).
3. Combined PCN/Beta-Lactamase inhibitors: Augmentin, Unasyn, Zosyn, Timentin – all have
excellent anaerobic activity, so no need to add Metronidazole (unless for C.diff). Unasyn better for
anaerobic infections above the waist, less so for intraabdominal infections (due to high rate of
resistance in E.coli).
4. Carbapenems (Imipenem, Meropenem, Ertapenem, Doripenem) – all have excellent anaerobic
activity.
5. 2nd Generation Cephalosporins (Cephamycins): Cefoxitin, Cefotetan – beware increasing
resistance of Bacteroides (Cefoxitin is better than Cefotetan, but avoid both for serious intraabdominal
infections)
6. Moxifloxacin – has data to support its use in intraabdominal infections, but beware increasing
resistance among Bacteroides (up to 40%!)
7. Tigecycline – excellent anaerobic activity.

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VIII. URINARY TRACT INFECTION-SPECIFIC ANTIBIOTICS

1. Nitrofurantoin (Macrobid) (PO)
Bactericidal agent that is excreted into urine, where its active metabolites attack multiple sites within
bacteria.
Spectrum: Broad spectrum vs Gram positives including Staph, Strep, Enterococcus (including some
VRE); most Gram negatives including some ESBL’s. No activity vs Pseudomonas.
Used for: only for lower tract UTI’s (cystitis). Generally given for 7 day course. Cannot use for
pyelonephritis (poor kidney tissue penetration).
Avoid for long-term use due to potential pulmonary side effects: Hypersentivity
Pneumonitis(occurs 7-10 days after therapy, usually resolves) and Chronic Pulmonary
Fibrosis (develops after several months of therapy, some recovery but often persistent
fibrosis)
Contraindicated in renal failure with CrCl < 60 (poor excretion into urine)

2. Fosfomycin (PO)
Bactericidal agent that is excreted into the urine and inhibits cell wall synthesis by interfering with
peptidoglycan synthesis.
Spectrum: Broad spectrum vs Gram positive including MRSA, VRE; Gram negative including Pseudomonas
and some ESBL’s.
Used for: Uncomplicated urinary tract infections in women, especially in those with history of resistant
bugs. Given as a one-time mega-dose of 3 g (excreted into urine and achieves high levels there for
several days. Sometimes used for complicated UTI’s in males with resistant pathogens (3 g PO q3 days x
several doses), although this is an off-label use.
Like nitrofurantoin, cannot use for pyelonephritis due to poor kidney tissue penetration.
Resistance develops rapidly – not suitable for sustained therapy for severe infections.
Minimal side effects and very well tolerated.

3. Methenamine (PO)
Antimicrobial agent that is converted to formaldehyde in the bladder, leading to bacteriostatic effect.
Requires acidic environment to work (pH < 5.5) so ineffective vs Proteus.

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Used for: prevention of recurrent UTI’s (as opposed to treatment of active infection).
Actual efficacy is controversial but some evidence to support use for short-term prophylaxis.
Long-term efficacy is unclear.
Contraindicated in renal failure – decreased excretion into urine leads to systemic accumulation
and toxicity.

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IX. ANTI-C.DIFFICILE ANTIBIOTICS

1. Metronidazole – (see anti-anaerobe section above for more details). First-line therapy for first or
second episode of mild-moderate C.difficile infection (defined as WBC <15 k, no acute renal failure). PO
preferred if able, but IV is also effective. IV form used for severe, complicated cases (e.g. ileus or toxic
megacolon) where absorption of PO vancomycin may be unreliable. Not recommended after 1st
relapse due to cumulative neurotoxic effect.
2. Oral Vancomycin – first-line therapy for severe C.diff infection (WBC >15k, or acute renal failure).
Shown to be superior in severe cases of C.diff vs Metronidazole (CID 2007).
Dose = 125 mg po q6 hours, or 250-500 mg po q6 hours for severe complicated disease (ileus,
hypotension, toxic megacolon), although no supporting evidence for this higher dose. Also
consider vancomycin enemas (and surgical consult) in those situations.
No systemic absorption, and thus no side effects (main side effect = cost!)
It is a myth that PO vancomycin increases risk of VRE compared to Metronidazole (both
increase the risk of VRE – Metronidazole disrupts anaerobic flora of the gut, promoting
overgrowth of VRE).

3. Fidaxomicin (PO)
Mechanism: new macrocyclic antibiotic with narrow spectrum of activity against only C.diff (inhibits
C.difficile RNA polymerases).
Minimal absorption and thus minimal side effects. Dose = 200 mg bid.
Noninferior (and likely superior) to oral vancomycin for initial treatment of C.difficile. Main
advantage is reduced rates of relapse, but this benefit not seen so far for NAP-1
strain. Also has higher cure rate when used in patients with C.diff who require continued
systemic antibiotic therapy for other reasons.

4. Other options - Rifaximin (sometimes used at the end of a prolonged course to prevent relapse in
high-risk patients), Nitazoxanide, Tigecycline (case reports of success). Non-antibiotic options include
IVIG, Monoclonal Antibody vs C.diff, stool transplant, and surgery.

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X. RIFAMYCINS – include Rifampin, Rifaximin, Rifapentine, Rifabutin.

Mechanism: Inhibits bacterial DNA-dependent RNA polymerase (unique mechanism).

1. Rifampin (PO and IV)
Spectrum: Broad spectrum including Mycobacteria and other intracellular pathogens, Gram positive
(Staph, Strep, Listeria), Gram negatives. Despite broad spectrum, only used for select indications.
Used for: Active TB (in combination with other drugs), Latent TB (2nd-line), N.meningitidis contact
prophylaxis, Staphylococcal prosthetic infections
Aside from its role in mycobacterial infections, Rifampin’s other main use is its adjunctive role
in treating Staphylococcal (both S.aureus and Coag-negative Staph) infections
involving prosthetic material (due to its unique ability to penetrate biofilms) -
prosthetic valve endocarditis, prosthetic joint infections, etc.
Resistance develops rapidly, so two important caveats: 1. Never use as monotherapy. 2. Do
not use for Staphylococcal infections until low burden of disease (i.e. after initial
induction period with IV therapy, debridement, etc).
Side effects: Orange discoloration of body fluids (urine, tears, sweat), hepatotoxicity, rare bone
marrow toxicity, rash. Multiple drug interactions (potent CYP inducer).

2. Rifaximin (PO)
Nonabsorbable analog of rifampin, used for treatment of traveler’s diarrhea, hepatic encephalopathy
(both in the acute phase and for long-term prophylaxis), and C.difficile infection (usually as a tail to a
prolonged taper).

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XI. IMPORTANT HOLES IN COVERAGE WITH VANCOMYCIN / ZOSYN

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Vanc/Zosyn is not elegant, but will cover most infections: Gram positives including MRSA, Gram
negatives including most Pseudomonas, and anaerobes. Excellent range of site penetration including
lungs, abdomen, urine, and skin/soft tissues. Not a bad choice if patient is very ill and unclear source of
infection.
But what does it not cover? I.e., what to worry about if pt spiking through Vanc/Zosyn – a selected list:
1) Atypical infections – Legionella, Chlamydia, Mycoplasma. Vanc/Zosyn is not adequate for
Community-Acquired Pneumonia.
2) VRE – suspect especially if patient previously on vancomycin
3) ESBL – think of this if patient has been hospitalized recently and received broad spectrum Abxs
4) Fungal infections – be on the lookout for this, esp if spiking through broad spectrum abxs, and
other risk factors (TPN, Central lines, Bowel surgery, Immunosuppressed/Neutropenic)
5) Clostridium difficile
6) Stenotrophomonas maltophilia – nonlactose fermenting gram negative rod that causes infections,
usually in ICU patients (esp with prior Carbapenem use) or immunocompromised.
7) Mycobacterial infections – especially consider in patients with “pneumonia” and high risk for TB
8) Viral Infections – Influenza, HSV/VZV/CMV etc. (esp in immunocompromised pts)
9) Parasites – consider your patient’s demographics
10) Any gram negative can develop resistance, and so can Staph – VISA, VRSA (very rare)
11) Source control – Abxs will not cure infection if source not controlled – undrained abscess,
infected line, empyema, etc.
12) Non-infectious causes of fever – DVT’s, hematoma, drug fever, malignancy, transfusion reactions,
pancreatitis, and more
Note: Typical “Step up” from Vanc/Zosyn à Linezolid/Meropenem – gains VRE and ESBL
coverage, also possibly better MRSA PNA coverage.

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ANTIFUNGALS
I. AZOLES
Mechanism: inhibit ergosterol synthesis (important component of fungal cell membranes)
Main metabolism is hepatic, main toxicity is elevated LFTs.
Only Fluconazole has adequate urinary penetration. Itraconazole has poor CNS penetration compared to the
others.

1. Fluconazole(PO or IV)
Drug of choice for non-severe Candida infections, including C.albicans, EXCEPT C.glabrata (can potentially
overcome with higher doses – check susceptibilities) and C.krusei (Kompletely resistant).
Also used for Cryptococcus infections (maintenance phase for cryptococcal meningitis after induction with Ampho B),
Coccidioidomycosis, Histoplasmosis (but inferior to Itraconazole), and others.
Toxicity: elevated LFTs, GI side effects
Good urine penetration – used for symptomatic candidal cystitis.
Best bioavailability of the azoles – if GI system intact, perfectly acceptable to treat even invasive candidiasis
with oral Fluconazole.
Selected dosing: Candidemia - 800 mg load then 400 mg qday. Thrush – 100 mg qday x 7 days. Esophageal
candidiasis - 200 mg qday or higher x 14-21 days. Dose reduce in renal failure.

2. Itraconazole(PO or IV)
Best activity among azoles vs Histoplasmosis – used for non-severe cases, and can also follow induction phase
with Ambisome for severe disease. Also used for Blastomycosis, sometimes Cocci and Paracocci infections, and
onychomycosis. Commonly used for prophylaxis in transplant patients
Toxicity: elevated LFTs and also negative inotrope – can worsen or cause CHF in predisposed pts (black box
warning)!
Many drug-drug interactions
Capsule form has poor bioavailability and absorption depends on acidic environment (avoid PPI/H2 blockers).
Liquid form is superior (must take with empty stomach)
Poor CNS penetration

3. Voriconazole(PO or IV)
Cidal for many molds à drug of choice for Invasive Aspergillosis! (appears to be superior to Ampho B and better
tolerated - NEJM 2002 ). Active vs Fusarium and Scedosporium. Also effective against most Candida, but little reason
to use over Fluconazole, and ~50% cross-resistance.
One important hole in coverage is no Zygomycetes (Mucormycosis)
Liver toxicity, also Visual toxicity – transient visual changes (common) and visual hallucinations (~4%, also
reversible). Encephalopathy with supratherapeutic levels.
Usually loaded intravenously, then can transition to oral form. If given long-term, need to check troughs to
ensure adequate dosing (goal trough 1-5).
Problem with IV form is that it is solubilized in cyclodextrin, which accumulates in renal failure (potentially
nephrotoxic).

4. Posaconazole(PO only)
Broad spectrum of activity: yeast (including many Fluconazole-resistant Candida), molds, endemic fungi,
zygomycetes (only azole other than Isavuconazole with activity). Fusarium is resistant in vitro.
Used as 2nd-line / salvage therapy for many severe fungal infections, and for fungal prophylaxis in high-risk patients

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(e.g bone marrow recipients).

Main problem is that it is only available PO, and must be given with fatty foods for maximal absorption .
Takes ~1 week to reach steady-state levels, and hence unsuitable for acute treatment of severe
fungal infections.
Similar toxicity profile as Fluconazole

5. Isavuconazole(PO or IV)
Newest triazole currently undergoing Phase III trials. Broad activity vs virtually all fungi (like Posaconazole) including
Candida, Aspergillus, Mucormycosis, Fusarium, Scedosporium, Cryptococcus.
Advantage over Posaconazole is that it has IV formulation as well as PO, so more suitable for initial therapy of
acute infection.
Advantage over Voriconazole is that the IV formulation does not require cyclodextrin, and thus safe to use in
renal failure.
Still undergoes CYP metabolism so problem with drug interactions. Similar toxicity as Fluconazole (well
tolerated) .

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II. ECHINOCANDINS
Mechanism: Inhibit glucan synthesis in fungal cell wall by blocking beta 1,3 D-glucan synthase à fungicidal agent. All
are IV only.
Cidal vs Candida -> Drug of choice for severe Candida infections – covers virtually all species including
Fluconazole-resistant C.krusei and C.glabrata. But higher MICs in vitro for C.parapsilosis (commonly
associated with TPN) – unclear significance as it still usually works clinically. Also, rare reports of resistance in
C.lusitaniae, C.guilliermondii.
Static vs Aspergillus -> 2nd-line for Aspergillus infections (often as combination therapy or as salvage therapy,
never as initial monotherapy)
All Echinocandins lack activity vs Cryptococcus, Zygomycetes, and Fusarium.
Remarkably non-toxic, but can rarely cause elevated LFTs, also GI upset (n/v)
Poor penetration into urine – not used for UTIs. Also, not much data on CSF penetration – not recommended
for fungal meningitis.
Not well studied for Candida endocarditis (prefer Amphoterecin)
All 3 agents are essentially interchangeable in terms of spectrum of activity

1. Caspofungin
First approved echinocandin. Load 70 mg IV qday, then 50 mg qday. Hepatically cleared.
2. Micafungin
Similar to Caspofungin. 100 mg daily, no loading dose. Hepatically cleared.
3. Anidulafungin
Newest echinocandin. Unique metabolism: chemically degraded in the blood, no hepatic or renal clearance à
safer in liver/renal failure. Also no significant drug-drug interactions.
Load 200 mg IV once, then 100 mg IV qday

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III. POLYENES – Amphoterecin B, Abelcet, Ambisome

Mechanism: binds ergosterol in membrane and forms membrane pores à fungicidal.
Drug of choice for many severe fungal infections: Zygomycetes, Cryptococcal Meningitis (induction phase with
flucytosine), Severe Histoplasmosis/Blastomycosis/Coccidioidomycosis
2nd-line for invasive aspergillosis (voriconazole is drug of choice). 2nd-line for candida infections – because
echinocandins are at least as effective, and less toxic.
Note that some candida are resistant, often C.lusitaniae and C.guilliermondi
Significant toxicity: Nephrotoxic (including Mg and K wasting), Hypotension, Bradycardia, Fevers/chills
during infusion (“shake and bake”), Seizures
Lipid preparations (Ambisome, Abelcet) are designed to reduce binding to mammalian cell membranes. They
are as effective as conventional Amphoterecin and less toxic (especially with renal toxicity), although
more expensive. Ambisome is less toxic than Abelcet. Nowadays, rarely use non-liposomal amphoterecin B.

IV. Flutycosine
Mechanism: 5-FC interferes with DNA and protein synthesis. Only available PO in the US
Used in combination with Amphoterecin B for initial management of several severe fungal infections:
Severe cryptococcal pneumonia and meningitis, severe candidal infections (endocarditis, meningitis)
Virtually never used as monotherapy due to high incidence of primary and acquired resistance
(monotherapy reserved for non-severe candida urinary tract infections)
Main adverse effects = Hematologic (Leukopenia and Thrombocytopenia) and Hepatic toxicity. Drug levels
should be monitored to reduce toxicity.

In Summary:
1. Mild-Moderate Candidemia -> Fluconazole
2. Severe Candidemia -> Echinocandin (> Amphoterecin)
** Other principles of management of Candidemia – remove central lines and foreign bodies, check ophtho
exam to evaluate for endophthalmitis, treat for minimum 14 days from clearance of blood cultures**
3. Invasive Aspergillosis -> Voriconazole (> Amphoterecin, Echinocandin as 2nd-line)
4. Mucormycosis à Amphoterecin B

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EMPIRIC ANTIBIOTIC CHOICES FOR COMMON INFECTIONS

Likely Pathogens Recommended Antibiotic Regimens and Typical
Condition Dose (for normal renal/hepatic function) Duration
PULMONARY
Community-Acquired S. pneumonia, 1. Ceftriaxone 1 g IV qday + Azithromycin 500 7-10 days.
Pneumonia (CAP) H.influenza, Intracellular mg, then 250 mg PO/IV qday Azithromycin
atypical organisms 2. Moxifloxacin 400 mg PO/IV or Levofloxacin can be given
(Mycoplasma 750 mg PO/IV qday. for 5 days, but
pneumoniae, *For severely ill patients, consider addition of longer if
Chlamydophila Vancomycin or Linezolid for coverage of confirmed
pneumoniae, Legionella), community-acquired MRSA. Legionella.
Respiratory viruses. *Consider anti-Pseudomonal coverage if risk
*S.aureus if IV drug user, factors present.
recent influenza.
*Pseudomonas if
structural lung disease
(e.g. bronchiectasis,
COPD with frequent
steroid use).
Hospital, Healthcare- S.aureus (including 1. Anti-MRSA antibiotic: Vancomycin 15-20 7-8 days, but
Associated, or MRSA) and aerobic gram mg/kg IV q12 hrs or Linezolid 600 mg PO/IV potentially
Ventilator-Associated negative rods including bid longer for
Pneumonia Pseudomonas aeruginosa, + MRSA or
(HAP, HCAP, VAP) E.coli, Klebsiella 2. Antipseudomonal Beta-Lactam: Ceftazidime 2 Pseudomonas
pneumonia, and g IV q8 hrs, Cefepime 2 g IV q8 hrs, or immuno-
Enterobacter species. Piperacillin/Tazobactam 4.5 g IV q6 hrs, compromised.
Multi-drug resistant Imipenem 500 mg IV q6 hrs or Meropenem 1-2 g 15 day course
(MDR) gram negatives are IV q8 hrs; Aztreonam 1-2 g IV q8 hrs if severe for
common in ICU patents. penicillin allergy. Pseudomonas
*Role of anaerobes, even *For severely ill patients, or if high risk of associated with
in nosocomial aspiration resistant gram negative infection, also consider decreased
pneumonia, is unclear addition of “double coverage” with recurrence of
(but reasonable to add Antipseudomonal Fluoroquinolone (Ciprofloxacin disease.
anaerobic coverage in that or Levofloxacin), or Aminoglycoside.
scenario).
Aspiration Pneumonia Oral anaerobes, enteric 1. Levofloxacin 750 mg PO/IV q24 hrs + 7-10 days
gram negative rods, Metronidazole 500 mg PO/IV q8 hrs, or
S.aureus, Streptococcus 2. Clindamycin 600 mg IV q8 hrs (add
species Levofloxacin if concern for community-acquired
pneumonia), or
3. Ampicillin/Sulbactam 3 g IV q6 hrs
*If nosocomial – treat as HAP, with preference
for Piperacillin/Tazobactam, Imipenem or
Meropenem for anaerobic coverage, or add
Clindamycin or Metronidazole.
GASTROINTESTINAL
Appendicitis, Polymicrobial GI flora 1. Ceftriaxone 1 g IV qday + Metronidazole 500 4-7 days for
Diverticulitis, including gram negative mg IV q8hrs, or Appendicitis or
Intraabdominal rods (especially E.coli) 2. Ciprofloxacin 400 mg IV q12 hrs or Diverticulitis.
Abscess, Secondary and anaerobes (especially Levofloxacin 500 mg IV 24 hrs + Metronidazole Duration for
Peritonitis Bacteroides). (caution with Cipro due to poor strep coverage), abscesses
For bowel perforation, or depends on
microbiology depends on 3. Piperacillin/Tazobactam 3.375 g IV q6 hrs, or adequate
site. Upper GI tract (e.g. 4. Imipenem 500 mg IV q6 hrs or Meropenem 1 drainage, but
perforated duodenal g IV q8 hrs. typically
ulcer) mainly *For severely ill or healthcare/hospital-acquired minimum 4-7
Streptococcus species. disease, consider addition of Enterococcal and days after
Lower GI tract mainly Candida coverage (especially if not responding to drainage.
gram negative rods and therapy).
anaerobes. *Caution with Ampicillin/Sulbactam alone due to
Enterococcus and Candida high rates of E.coli resistance at some
species usually less institutions.
important, except in
healthcare-associated
cases.
Spontaneous Bacterial Gram negative rods Cefotaxime 2 g IV q8 hrs or Ceftriaxone 1 g IV q 5-7 days
Peritonitis (SBP) in including E.coli, Klebsiella, 24 hrs
patients with ascites Enterobacter. Also, + Albumin 1.5 g/kg on day 1 and 1 g/kg on day
enteric Streptococci and 3
Enterococci.
Cholangitis Polymicrobial GI flora. Ceftriaxone 1 g IV qday, Ciprofloxacin 400 mg 4-7 days
Anaerobes if biliary- IV bid, or Levofloxacin 500 mg IV qday assuming
enteric anastomosis. + Metronidazole 500 mg IV q8 hrs if biliary- adequate
Enterococcus coverage enteric anastomosis. source control.

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usually not required. If severe or healthcare-associated infection,

consider Piperacillin/Tazobactam or Imipenem or
Meropenem.
URINARY
Acute cystitis E.coli is most common, 1. Bactrim DS 1 tb po bid x 3 days, or 3 days
followed by also other 2. Nitrofurantoin 100 mg po bid x 5 days
gram negatives (Proteus, (contraindicated in renal failure), or
Klebsiella, Serratia, 3. Fosfomycin 3 g po x 1 dose
Enterobacter) and Staph *Avoid Nitrofurantoin and Fosfomycin if
saphrophyticus pyelonephritis is a possibility (do not penetrate
kidney tissue).
*Ciprofloxacin is 2nd-line due to high rates of
resistance (and should be reserved for other
purposes).
Acute pyelonephritis Same as for acute cystitis. 1. Ceftriaxone 1 g IV q24 hrs, or 7-10 days
2. Ciprofloxacin 400 mg IV q12 hrs or
Levofloxacin 500 mg IV q24 hrs (2nd-line due to
resistance), or
3. Cefepime 1 g IV q12 hrs (especially if prior
resistant organisms or Pseudomonas)
Complicated UTI More likely to be due to 1. If mildly ill – Ciprofloxacin 400 mg IV q12 hrs 10-14 days
(defined by presence of resistant gram negatives or Levofloxacin 500 mg IV q24 hrs or Ceftriaxone (Longer if
anatomic or functional including ESBL’s and 1 g IV q24 hrs. suspect
abnormality in GU tract, Pseudomonas. Staph 2. If severely ill - Cefepime 1 g IV q12 hrs, or prostatitis)
or urinary catheter) aureus is possible if Ceftazidime 1 g IV q8 hrs, or carbapenem if high
chronic urinary catheters risk for ESBL, or history of prior infections.
or stents. Also: Consider adding Vancomycin especially if history
Enterococcus, Candida. of prior infection, chronic urinary catheters or
stents.
SKIN AND SOFT TISSUE
Cellulitis Streptococcus species 1. Oral options: Cephalexin 500 mg po q6 hours, 7-14 days
(most commonly Group Clindamycin, Dicloxacillin.
A), S.aureus including Add MRSA coverage if purulent or severe
MRSA. disease. Oral options include Bactrim 2 DS tabs
More unusual pathogens bid (best) or Doxycycline 100 mg po bid (both
are possible depending on have poor strep coverage so should be paired
risk factors (i.e. water with one of the oral beta-lactams). Clindamycin
exposures, animal bites, is an option but CA-MRSA resistance can exceed
neutropenia). 50%.
2. IV options for Strep, low suspicion for MRSA:
Cefazolin 1 g IV q8 hrs, Clindamycin 600 mg IV
q8 hrs.
3. IV options with MRSA coverage: Vancomycin
15-20 mg/kg IV q12 hrs, Linezolid 600 mg
PO/IV q12 hrs, Daptomycin 4-6 mg/kg IV q24
hrs, Clindamycin 600 mg IV q8 hrs (but MRSA
often resistant)
Infected Diabetic Foot Streptococcus species, 1. Moderate disease - Ceftriaxone 1 g IV qday, 7-21 days if no
Ulcer S.aureus including MRSA, Levofloxacin 750 mg po/IV qday, or Cefepime 1 evidence of
Gram negative rods g IV q8 hrs, all with Metronidazole 500 mg po/IV osteomyelitis.
(E.coli, Klebsiella, q8 hrs.
Proteus, Pseudomonas), 2. Severe disease: Vancomycin 15-20 mg/kg IV
anaerobes. q12 hrs, and anti-Pseudomonal beta-lactam
(Ceftazidime 2 g IV q8 hrs, Cefepime 2 g IV q8
hrs, or Aztreonam 2 g IV q8 hrs with
Metronidazole 500 mg q8 hrs, or
Piperacillin/Tazobactam 4.5 g IV q6 hrs or
Imipenem 500 mg IV q6 hrs or Meropenem 1 g
IV q8 hrs).
Necrotizing Fasciitis Type I is polymicrobial In addition to emergent surgical debridement: Depends on
(Streptococci, Gram 1. Anti-MRSA agent: Vancomycin 15-20 mg/kg clinical course
negatives) and also IV q12 hrs, consider loading dose of 25-30 (should
involves anaerobes. mg/kg, or Linezolid 600 mg IV q6 hrs, or continue at
Type II is due to beta- Daptomycin 6 mg/kg IV q24 hrs least until no
hemolytic strep (usually + more surgical
group A strep), less 2. Broad spectrum beta-lactam: debridement
commonly CA-MRSA. Piperacillin/Tazobactam 4.5 g IV q6 hrs, necessary and
Imipenem 500 mg IV q6 hrs, Meropenem 1 g IV minimum of
q8 hrs alone, 10-14 days.
or Cefepime 2 g IV q8 hrs + Metronidazole 500
mg IV q8 hrs.
* Consider addition of Clindamycin 600-900 mg
IV q8 hrs for antitoxin effect vs Strep and
Staph. IVIG may be beneficial in cases due to
Group A Strep.

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MUSCULOSKELETAL
Septic Arthritis S.aureus including MRSA, In addition to surgical drainage, empiric 2-4 weeks
Streptococcus species antibiotics based on gram stain:
(especially Group B strep 1. Gram positive cocci in clusters (likely
in diabetics), S.aureus): Vancomycin 15-20 mg IV q12 hrs
N.gonorrhoeae (triad of 2. Gram negative cocci (likely Neisseria):
pustular skin lesions, Ceftriaxone 1 g IV qday
tenosynovitis, arthritis), 3. Gram negative rods: Cefepime 1 g IV q8 hrs
Gram negative rods or Ceftazidime 1 g IV q8 hrs
(Pseudomonas if IVDU). 4. Negative gram stain – Vancomycin +
Ceftriaxone, or Vancomycin + Cefepime or
Ceftazidime if risk factors for Pseudomonas.
CENTRAL NERVOUS SYSTEM
Bacterial Meningitis, S.pneumo, N.meningitidis, Ceftriaxone 2 g IV q12 hours + Vancomycin 15- Duration
Community-Acquired H.influenza species. 20 mg/kg IV q8 hrs (target trough ~20 depends on
Listeria if risk factors: Age mcg/mL). pathogen
>50, *Add Ampicillin 2 g IV q4 hours if at risk for (range 7-21
Immunocompromised Listeria. days).
*If severe beta-lactam allergies: Vancomycin + Steroids should
Moxifloxacin or Chloramphenicol (+ Bactrim if be stopped
risk for Listeria). after 4 days, or
*Consider Dexamethasone 0.15 mg/kg IV q6 if proven to be
hrs, 15-20 minutes prior to antibiotics, in adults due to another
with suspected pneumococcal meningitis. organism.
Nosocomial Meningitis S.aureus, Coagulase- Vancomycin 15-20 mg/kg IV q8 hrs Duration
negative staph, Gram + Cefepime 2 g IV q8 hours or Ceftazidime 2g IV depends on
negative rods including q8 hours or Meropenem 2g IV q8 hours pathogen
P.aeruginosa
BLOODSTREAM
Catheter-associated S.aureus, Coagulase- Vancomycin 15-20 mg/kg IV q8 hrs Depends on
bloodstream infection negative staph, *Consider addition of Cefepime 1-2 g IV q8 hrs, pathogen
Enterococci, Gram Piperacillin-Tazobactam 4.5 g IV q6 hrs, (range 7-14
negative rods (more likely Imipenem 500 mg IV q6 hrs or Meropenem 1 g days if
with femoral lines or ICU IV q8 hrs if severely ill, or suspected source is a otherwise
patient), Candida femoral line, or otherwise at risk for resistant uncomplicated
(especially if on TPN) gram negatives. course). 14
*Consider echinocandin (e.g. caspofungin) if days is a
severely ill and high risk of Candida (e.g TPN, minimum for
immunocompromised) S.aureus
infections.
OTHER SYNDROMES
Neutropenic fever Oral and enteric 1. Cefepime 2 g IV q8 hours Depends on
streptococci, gram 2. Alternatives: Piperacillin/Tazobactam 4.5 g IV duration of
negative rods including q6 hrs, Imipenem 500 mg IV q6 hrs or neutropenia
Pseudomonas, Candida. Meropenem 1 g IV q8 hrs and resolution
S.aureus or coagulate- *If severe beta-lactam allergy: Levofloxacin + of fever
negative staph in patients Aztreonam
with indwelling lines. *Add Vancomycin if: Hypotensive or severely ill,
pneumonia, suspected catheter-related infection,
known colonization with MRSA or PCN-resistant
Strep, recent prophylaxis with fluoroquinolones.
Discontinue Vancomycin if no evidence of MRSA
after 48 hours
*Add antifungal (Echinocandin, Voriconazole, or
Amphotericin B) if persistently febrile after 4-7
days despite antibacterial therapy
Severe Sepsis of Both gram positive and Vancomycin 15-20 mg IV q12 hrs with loading Depends on
Unknown Source gram negative organisms dose of 25-30 mg/kg IV, or Linezolid 600 mg clinical course
should be targeted PO/IV if contraindication to Vancomycin, or and
Daptomycin 6 mg/kg IV q24 hrs if do not suspect identification of
pulmonary source source
+ Anti-Pseudomonal beta-lactam (Cefepime 2 g
IV q8 hrs, Ceftazidime 2 g IV q8 hrs,
Piperacillin/Tazobactam 4.5 g IV q6 hrs,
Imipenem 500 mg IV q6 hrs, or Meropenem 1 g
IV q8 hrs)
+/- Anti-Pseudomonal Fluoroquinolone
(Ciprofloxacin 400 mg IV q12 hrs or Levofloxacin
750 mg IV q24 hrs), or Aminoglycoside, or
Aztreonam 1-2 g IV q8 hrs

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