Antibiotics Review


Source: Stanford Medicine:

Antibiotic Dosing and Antibiogram for LPCH (2018), courtesy of Stanford/LPCH Antibiotic Stewardship Program










VIII. Urinary Tract Infection-Specfic Antibiotics


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

XI. Last Tidbit: Very common antibiotic regimen = VANCOMYCIN / ZOSYN






I.  BETA-LACTAMS = PCNs, Cephalosporins, Carbapenems, Monobactam(Aztreonam)

Overview of Beta-Lactam Allergies:


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.

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. 

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).


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. 

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. 

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.  

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

Spectrum (General Rules):

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).

2nd Generation

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

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. 

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


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.

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)

D. CARBAPENEMSImipenem/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

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. 

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.


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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.   


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. 


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)


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

Spectrum: Extremely efficacious vs. aerobic Gram negatives including PseudomonasNO 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).


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.

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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.

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.

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)


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.


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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.

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

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)

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.

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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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.

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.

*Treatment of HCAP/HAP/VAP in patients with high risk of MDR organisms: Essential to empirically treat for MRSA, and Gram negatives including Pseudomonas *

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Infections in which anaerobes are likely to play an important role include (from head to toe):

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.

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, Timentinall 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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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).

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.

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.

Used for: prevention of recurrent UTI’s (as opposed to treatment of active infection).

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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).  

3. Fidaxomicin (PO)

Mechanism: new macrocyclic antibiotic with narrow spectrum of activity against only C.diff (inhibits C.difficile RNA polymerases). 

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

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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From Lewis RE et al, Mayo Clinc Proc 2011


Mechanism:  inhibit ergosterol synthesis (important component of fungal cell membranes)

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.

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

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. 

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 (e.g bone marrow recipients).

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.

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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.glabrataBut 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.

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 àsafer 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.

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)

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