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Master List
ANTIBACTERIALS
Cardiology I. BETA-LACTAMS
II. PROTEIN SYNTHESIS INHIBITORS
ANTIFUNGALS
Nephrology
I. AZOLES
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.
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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
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.
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
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.
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).
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.
3rd Generation
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.
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.
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.
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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.
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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.
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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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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).
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).
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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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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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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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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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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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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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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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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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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