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ANTIBIOTICS REVIEW

I. BETA-LACTAMS = PCNs, Cephalosporins, Carbapenems, Monobactam(Aztreonam) - Cell wall inhibitors: bind PBPs (Penicillin-binding proteins) in cell membrane and inhibit cell wall crosslinking bactericidal. - Main side effects: Hypersensitivity reactions including anaphylaxis, Rashes, Bone marrow suppression, Interstitial Nephritis, GI (nausea, diarrhea, and C.diff) A. PENICILLINS 1st Generation = PENICILLIN G (IV) or V (PO) - used for Group A Strep (e.g. Strep throat), Syphilis, PCN sensitive streptococcus; also gets most oral anaerobes 2nd Generation = AMPICILLIN (IV), AMOXICLLIN (PO) - covers some Gram (+) and Gram (-), but not Pseudomonas. Used for Enterococcus (non-VRE), Listeria, Group B Strep, UTIs, and more. Amoxicillin often used for upper respiratory infections (e.g. sinusitis, otitis media) 3rd Generation = Anti-Staph PCNs: METHICILLIN / NAFCILLIN / OXACILLIN (IV), DICLOXACILLIN (PO) - Nafcillin is drug of choice for MSSA. Good for cellulitis, osteomyelitis, endocarditis (IV only). No MRSA coverage, little activity/ unreliable vs. Coag(-) Staph. 4th Generation = Anti-pseudomonal PCNs - PIPERACILLIN, TICARCILLIN - usually combined with beta lactamase inhibitors (see below) COMBINED PCN/BETA-LACTAMASE INHIBITORS: gains broader coverage including anaerobes 1) AUGMENTIN(Amoxicillin/Clavulanate = PO) , UNASYN (Ampicillin/Sulbactam = IV) Gram (+), Gram (-), Anaerobes, but NO Pseudomonas. Used for variety of infections, including respiratory infections, some skin/soft tissue infections, some intraabdominal infections, and more. 2) ZOSYN (Piperacillin/Tazobactam), TIMENTIN (Ticarcillin/Clavulanate) as above, but also covers Pseudomonas. Many uses: Hospital-acquired PNA, Severe skin/soft tissue infections including diabetic ulcers, empiric sepsis, intraabdominal infections. Great empiric drug. - Does NOT cover: MRSA, VRE, Atypicals (Chlamydia, Mycoplasma, Legionella), ESBLs. - Note higher dosing for PNA/Pseudomonas coverage: 4.5 g q6 hrs (vs. 3.375 q6 for other) - Extended Infusion strategy 3.375 g over 4 hours, q8 hrs - ? better outcomes for rx of Pseudomonas infections compared to standard dosing? Goal to maximize time above MIC. B. CEPHALOSPORINS - higher resistance to beta-lactamases better anti-staph activity - Estimated ~10% cross-reactivity with PCN allergy, but less with higher gen cephalosporins. (More recent studies suggest that of pts with (+) skin testing to PCN, only ~ 2 % will react to cephalosporins.) Note: No Cephalosporin covers Enterococcus or Atypicals. Only Ceftazidime/Cefepime cover Pseudomonas. Only Cefoxitin and Cefotetan have anaerobic coverage. 1st Gen = CEFAZOLIN (Ancef or Kefzol) - IV, CEPHALEXIN (Keflex) - PO - Excellent Gram(+) (MSSA and strep) , minor Gram (-) = Proteus, E.coli, Klebsiella. Good drug for cellulitis (unless suspect MRSA), also Cefazolin used for prophlaxis during surgery. Sometimes used for UTIs as well. 2nd Gen: a.CEFUROXIME - gram(+) and more gram (-) for respiratory infections and more b.CEPHAMYCINS = CEFOXITIN and CEFOTETAN -ANAEROBES (esp Bacteroides) and gram negatives, not pseudomonas or gram (+). Used for intraabdominal infections, like cholecystitis. Cefotetan can cause elevated INR. 3rd Gen: a. CEFTRIAXONE (Rocephin), CEFOTAXIME = IV, CEFPODOXIME= PO - good gram(+) and gram(-), but not pseudomonas or anaerobes . Used for Community Acquired PNA (with Azithromycin), Meningitis (CTX - excellent CSF penetration), Spontaneous Bacterial Peritonitis, Skin/Soft tissue infections, Bacteremia/Endocarditis from susceptible strep and enterococcus, and more. b. CEFTAZIDIME (IV)- only Gram(-) including Pseudomonas, virtually no Gram (+). Used for pseudomonal infections, also can be used for neutropenic fever (but beware no staph/strep coverage). 4th Gen = CEFEPIME (IV) - broad spectrum: gram (+) and gram (-) including pseudomonas, but weak anaerobes. Used for empiric neutropenic fever, hospital acquired PNA, meningitis if suspect gram negatives, and more. (5th Gen = CEFTOBIPROLE (IV) broadest spectrum gram (+) including MRSA and enterococcus, gram (-) including pseudomonas. Still awaiting approval in the U.S.) C. CARBAPENEMS = IMIPENEM/CILASTIN, MEROPENEM, ERTAPENEM, DORIPENEM - Broadest spectrum antibiotics, cover Gram(+), Gram(-) including Pseudomonas (except Ertapenem) and ESBL (extended spectrum beta lactamase producers), also anaerobes. Great penetration virtually everywhere, including CSF. Only class that reliably covers ESBL producing organisms - Very broad easier to remember what it doesnt cover: MRSA,VRE, Atypicals, Stenotrophomonas - Note that Ertapenem does NOT cover Pseudomonas, but does still cover ESBL - (main advantage is once/ day dosing - great outpatient IV drug). - Doripenem newest carbapenem, main advantage = increased in vitro potency against Pseudomonas - Cross-reactivity with PCNs previously thought to be fairly high (up to 40%), but ? - more recent studies suggest that vast majority with PCN allergies will tolerate Carbapenems? - Main additional side effect = Lower seizure threshold greatest risk w/ Imipenem, less w/ Meropenem
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D. MONOBACTAM = AZTREONAM - only has activity vs. aerobic gram negatives, no gram positive or anaerobes = very similar coverage as Aminoglycosides. Used most often in PCN allergic patients. Almost no significant toxicity. - main advantages:1) No cross-reactivity with PCN allergy, and 2) Does not cause renal failure - Has similar side chain as Ceftazidime if Ceftaz allergy, avoid Aztreonam! II. PROTEIN SYNTHESIS INHIBITORS bind to either 30 S or 50 S ribosomal unit. Most are bacteriostatic, except for Aminoglycosides generally considered cidal, due to irreversible binding, but also ?disruption of outer cell membrane?. A. MACROLIDES = 50S Ribosomal Inhibitor - bacteriostatic - ERYTHROMYCIN, CLARITHROMYCIN, AZITHROMYCIN - Azithromycin is drug of choice for Atypical coverage (Chlamydia, Mycoplasma, Legionella), also some activity vs. Gram(+) cocci and some gram(-). Commonly used for low-risk bronchitis or community-acquired pna, sinusitis, and others. Used in conjunction with Ceftriaxone for CAP that requires hospitalization. Used for MAC ppx in HIV/AIDS patients. Also used for STD Chlamydia. - 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) Side effects: QT prolongation, GI side effects, Rash B. TETRACYCLINES - 30S Inhibitors, bacteriostatic -TETRACYCLINE, DOXYCYCLINE, MINOCYCLINE -Great for atypicals, weird things such as Rickettsia, Lyme disease, Tularemia, Vibrio, Brucella, also Acne and rosacea -Weakly broad spectrum vs. Gram(+) and some Gram(-) - reasonable choice for low risk outpatient respiratory infections. Also for some community-acquired MRSA skin infections. -Side Effects: photosensitivity, GI discomfort, teeth discoloration, inhibits bone growth in children, teratogenic, steatosis and hepatotoxicity C. CLINDAMYCIN 50 S inhibitor, bacteriostatic - Excellent activity vs. Anaerobes and Gram positive cocci Strep and Staph, including ~ 50% of community-acquired MRSA, but NOT enterococci. Beware increasing resistance among Bacteroides. - Reasonable empiric drug for cellulitis due to Strep/Staph coverage, but beware of resistant MRSA. Also used often for its Antitoxin effect in Toxic Shock Syndrome or Necrotizing Fasciitis due to Group A Strep. Does not penetrate CSF. - Traditionally causes highest rate of C.diff among all Abxs (~10%). - If MRSA appears susceptibile always have lab check D-test looks for inducible resistance to Clindamycin in strains that are resistant to Erythromycin. If D-test positive, do not use Clindamycin. D. AMINOGLYCOSIDES = 30S inhibitor - bactericidal. - GENTAMICIN, TOBRAMYCIN, AMIKACIN, STREPTOMYCIN - extremely efficacious vs. aerobic Gram (-)'s only including Pseudomonas, NO activity vs. Gram(+) or anaerobes. - Can be used with beta-lactams against gram(+) for synergistic effect, especially in Endocarditis (best evidence for Strep and Enterococcal Endocarditis, less for Staph aureus optional for max 3-5 days for staph endocarditis). Poor urine and CSF penetration. Also less effective at low pH such as in lung/bronchial secretions not great for PNA (avoid monotherapy). - Can be used as double coverage agent vs gram negatives with Beta lactam for Hospital Acquired PNA - 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) - Dosing methods: Traditional Dosing q8-q12 hr dosing, vs 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 -Side effects: Nephrotoxicity - Acute Tubular Necrosis (classically manifests after ~ 5 days) and Ototoxicity may be irreversible !!! III. FLUOROQUINOLONES = DNA Gyrase and Topoisomerase inhibitors bactericidal 1) CIPROFLOXACIN - best gram(-) coverage of FQs, but virtually no gram(+) coverage. ALL fluoroquinolones have atypical coverage (but Cipro relatively weaker against Chlamydia and Mycoplasma, but good vs Legionella). Used for many purposes (UTIs, double coverage of Pseudomonas including for Hospital acquired PNA, prostatitis, GI/intraabdominal coverage - often with Flagyl). Not used in communityacquired PNA due to lack of Strep pneumo coverage. 2) LEVOFLOXACIN (Levaquin) Respiratory Fluoroquinolone - excellent activity vs. Gram (+) in particular Strep pneumo, slightly less reliable Pseudomonas coverage than Cipro. Not typically recommended for Staph aureus infections. Good for atypicals. Used for Community Acquired PNA (can use as monotherapy), also UTIs and double coverage of Pseudomonas including hospital acquired PNA. 3) MOXIFLOXACIN (Avelox) - also a Respiratory FQ- main difference vs. Levofloxacin is virtually NO urine activity (can't use for UTIs) and NO Pseudomonas activity no role in hospital/healthcare associated PNA. Best gram positive, atypical, and anaerobic coverage out of FQs also approved for complicated intraabdominal infections -FQs also have excellent TB coverage (esp Moxifloxacin) if patient with PNA, but suspect TB, do not use FQs!! (Do not want to use monotherapy against TB --> will develop resistance)
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Side Effects: QT prolongation, Tendon rupture (esp if on steroids), Cartilage damage, rare dysglycemias (Gatifloxacin removed from market for this reason), dizziness/HAs, Rashes, teratogenic IV. SULFONAMIDES = BACTRIM/SEPTRA (TMP/SMX) - inhibit sequential steps in Folate synthesis --> bacteriostatic - Uses: PCP PNA (drug of choice), Community-acquired MRSA Skin infections, UTIs, Nocardia, Listeria, gram(+), Gram(-) including Salmonella and Shigella, Stenotrophomonas - Note: good choice for cellulitis due to MRSA coverage (best CA-MRSA coverage out of oral Abxs except for Linezolid), but weak strep coverage --> consider adding Cephalexin for strep Many side effects: Bone marrow suppression, Interstitial Nephritis and ATN, Hyperkalemia, Aseptic Meningitis, Hypersensitivity (sulfas) and rashes, Hemolysis in G6PD deficiency, Falsely elevated creatinine (blocks Cr secretion into tubules), Transaminitis/cholestasis V. NITROFURANTOIN (MACROBID) - excreted into urine, where its active metabolites attack multiple sites within bacteria. Only used for UTIs (cystitis), not pyelenephritis or any other infection - reliable activity vs E.coli and Staph saphropyticus, also some Enterococcus including VRE, and some other gram negatives - Not used much anymore due to potentially very bad side effects: Hypersentivity Pneumonitis and Chronic Pulmonary Fibrosis. Contraindicated in renal failure.

VI. SUPER GRAM POSITIVE ANTIBIOTICS


- cover both MRSA and VRE (except Vancomycin), also Coag-negative staph, Strep, Enterococcus 1) VANCOMYCIN glycopeptide - mechanism: inhibits cell wall synthesis in Gram positives (different protein than beta lactams D-Ala-D-Ala) slowly cidal drug (compared to beta-lactams), but static vs Enterococcus - Covers staph/strep/nonVRE enterococcus. No gram negative coverage. Used for all sorts of gram positive infections including bacteremia, meningitis, PNA, skin/soft tissue, and more. - Not as effective as Nafcillin against MSSA, due to slowly cidal nature - PO form is not absorbed used for severe C.diff infections (shown to be superior to Flagyl) - Side effects: Red man syndrome (due to histamine release slow infusion rate), Low rate of nephrotoxicity (ATN) and ototoxicity (reversible), bone marrow suppression: leukopenia > thrombocytopenia - Dosing typical = 15 mg/kg (Actual body weight) q12 hrs. Often dosed by levels, must adjust for renal function, check trough prior to 4th dose. Goal trough 15-20 for severe MRSA infections, 10-15 for most other infections including cellulitis, Coag negative staph 2) LINEZOLID (Zyvox) oxazolidinone class unique ribosomal inhibitor (acts on 50S subunit), covers all gram positives including strep, MRSA and VRE. Bacteriostatic. - Has both PO and IV form. May be better for MRSA pneumonia than Vancomycin based on 2 recent trials better lung penetration and antitoxin effect? Approved by IDSA guidelines for empiric HAP/VAP/HCAP. Also has good TB coverage. - Side effects: Expensive! Also Bone marrow suppression especially thrombocytopenia. Also, is a MAO inhibitor possible risk of serotonin syndrome with SSRIs. Long term usage can lead to mitochondrial toxicity lactic acidosis, peripheral neuropathy, optic neuritis and blindness. - Another problem = static drug - not typically used for endocarditis. 3) DAPTOMYCIN new lipopeptide antibiotic forms transmembrane channels and depolarizes cells = rapidly cidal drug. Only IV form. - Only covers gram positives including MRSA and VRE, no gram negative activity. Indicated for skin/soft tissue infections, also being used more for bacteremia/endocarditis (due to cidal nature)and more - Main problem - no activity in lung parenchyma due to inactivation by surfactant useless for PNA! - Main side effect = muscle toxicity check weekly CK. - Dosing depends on infection 6 mg/kg qday for bacteremia, 4 mg/kg qday for skin/soft tissue infections. However, often use even higher doses for severe infections. 4) SYNERCID (Quinupristin/Dalfopristin) Streptogramins inhibits sequential steps in ribosomal synthesis covers MRSA and VRE due to E.faecium. Does not cover E.faecalis (has natural efflux pump). - Not used much - poorly tolerated due to thrombophlebitis at IV site generally need central line. Also severe myalgis/arthralgias and lots of drug-drug interactions (CYP450 inhibitor) 5) TIGECYCLINE - structurally related to Tetracyclines = new glycylcycline Abx - Broad spectrum Gram (+) including MRSA and VRE, gram negative, anaerobes, and atypicals. NO Pseudomonas or Proteus. Static drug. Used mostly for intraabdominal infections, but also PNA, skin/soft tissue infections.
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- Usually kept in reserve for serious and resistant infections please call ID before ordering this - Main side effects = GI (nausea/vomiting/diarrhea) and elevated LFTs

VII. SUPER GRAM NEGATIVE ANTIBIOTICS THAT COVER PSEUDOMONAS


- For serious infections due to suspected Pseudomonas, generally recommended to double cover with 2 antibiotics until susceptibilities identified, then narrow appropriately to one drug. Double coverage involves a beta-lactam plus either Fluoroquinolone or Aminoglycoside. Use Aztreonam if PCN-allergic. - Listed is the In-vitro activity vs Pseudomonas at Stanford (based on 2009 antibiogram) Note: only Cipro/Levofloxacin come in PO form, all other IV 1) 2) 3) 4) 5) Zosyn(Piperacillin/Tazobactam) - 93% Carbapenems Meropenem - 90%, Imipenem ~ 83%. Remember: Ertapenem has no activity. Ceftazidime, Cefepime (4th gen cephalosporin) 81% Aztreonam - 74% Fluoroquinolones -Ciprofloxacin (~74% coverage) > Levofloxacin (~70%), NOT Moxifloxacin (0%) - usually used as double coverage, not for monotherapy for empiric Pseudomonas treatment. ** FQs are the only PO drugs that have Pseudomonal coverage ** 6) Aminoglycosides Amikacin (94%), Tobramycin (97%), Gentamicin (82%), - never use as monotherapy vs Pseudomonas (shown to have worse outcomes) only as 2nd agent added to primary beta lactam therapy 7) COLISTIN polymyxin antibiotic that changes bacterial membrane permeability cidal. Kept in reserve for multidrug-resistant gram negatives, usually Pseudomonas and Acinetobacter. Often used in Cystic Fibrosis patients with resistant gram negative infections, sometimes used in aerosolized form. Had been abandoned for routine use due to its toxicity = Nephrotoxicity and Neurotoxicity, but experiencing a comeback due to rise in resistant gram negatives.

VIII. ANTIBIOTICS WITH ANAEROBE COVERAGE


1) METRONIDAZOLE (FLAGYL) mechanism: selectively taken up by anaerobic bacteria, reduced by proteins in the electron transport chain, and then disrupts DNA Active vs anaerobes (including C.diff), and protozoans: Giardia, Trichomonas, Entameba histolytica, also Helicobacter pylori (part of triple therapy). Classically for anaerobes below the diaphragm mainly due to weak coverage of Peptostreptococcus (gram positive oral anaerobe) Controversial: Some believe that it has better abscess penetration than other anti-anaerobic abxs --> may see pts with intraabdominal infections put on Zosyn + Flagyl 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 2) Clindamycin better for gram positive anaerobes. Classically for infections above the diaphragm mainly due to some resistance among Bacteroides species (gram negative anaerobes from GI tract) 3) Combined PCN/Beta-Lactamase inhibitors: Augmentin, Unasyn, Zosyn, Timentin 4) Carbapenems (Imipenem, Meropenem, Ertapenem, Doripenem) 5) 2nd Generation Cephalosporins (Cephamycins): Cefoxitin, Cefotetan 6) Moxifloxacin shown to be roughly equivalent to Zosyn for intraabdominal infections 7) Tigecycline

IX. (VERY) BROAD SPECTRUM ANTIBIOTICS


Definition: Cover both Gram(+) (MSSA, Strep) and Gram(-) including Pseudomonas Do NOT cover: MRSA, VRE, Atypicals, among others 1) Cefepime main weakness is weak anaerobe coverage, also Enterococcus 2) Zosyn (Piperacillin/Tazobactam) broader due to excellent anaerobe coverage, some nonVRE enterococcus 3) Carbapenems (except Ertapenem) broadest yet due to strong anaerobes, some enteroccocus, plus ESBL

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


- 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 1) Atypical infections (i.e. 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 8) Viral Infections Influenza, HSV/VZV/CMV etc. (esp in immunocompromised pts) 9) Parasites 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, perforated bowel, etc. **Dont forget about non-infectious causes of fever DVTs, hematoma, drug fever, malignancy, transfusion reactions, pancreatitis, and more Note: Typical Step up from Vanc/Zosyn Linezolid/Meropenem gains VRE and ESBL coverage, also better MRSA PNA coverage As you can see ID is not as as simple as Vanc/Zosyn!!

ANTIFUNGALS
I. AZOLES inhibit ergosterol synthesis (important component of fungal cell membranes) - main metabolism is hepatic, main toxicity is elevated LFTs 1) FLUCONAZOLE - Drug of choice for non-severe Candida infections, including C.albicans, EXCEPT C.glabrata (can overcome with higher doses) and C.krusei (Kompletely resistant) - Also used for Cryptococcus infections (maintenance phase for cryptococcal meningitis after induction with Ampho B), Coccidioidomycosis, Histoplasmosis, and others - Toxicity: elevated LFTs, also GI side effects - Great CSF and urine penetration (only azole with good urine penetration) 2) ITRACONAZOLE - used for non-severe Histoplasmosis, also Blastomycosis, sometimes Cocci and Paracocci infections - Also used for onychomycosis. - Commonly used for ppx in transplant patients - Toxicity: LFTs and also negative inotrope can worsen or cause CHF in predisposed pts (black box warning)! 3) VORICONAZOLE - Cidal for many molds --> drug of choice for Invasive Aspergillosis! (?superior to Ampho B and better tolerated in RCT- NEJM 2002 ) - Also effective against most Candida, but little reason to use over Fluconazole - One important hole in coverage is no Zygomycetes (Mucormycosis) - Liver toxicity, also Visual toxicity transient visual changes, but also rare visual hallucinations 4) POSACONAZOLE - newest azole with broad spectrum of activity: yeast, molds, endemic fungi, zygomycetes (only azole with activity) - main problem is that it is only available PO, and must be given with fatty foods for maximal absorption - used as 2nd-line / salvage therapy for many severe fungal infections - also used as ppx in some BMT centers II. ECHINOCANDINS - relatively new class of antifungals (Caspofungin approved in 2001) - inhibit glucan synthesis in fungal cell wall by blocking beta 1,3 glucan synthetase - remarkably non-toxic, but can rarely cause elevated LFTs, also GI upset (n/v)

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- 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, but reports of treatment failure. - Also used 2nd-line for Aspergillus infections (often as combination therapy, never as monotherapy) 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. Used at PAVA 3) ANIDULAFUNGIN - newest echinocandin. Great due to metabolism: chemically degraded in the blood, no hepatic or renal clearance safe in liver/renal failure. Also no significant drug-drug interactions. - load 200 mg IV once, then 100 mg IV qday III. AMPHOTERECIN B - Polyene binds ergosterol in membrane and forms membrane pores - 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 DOC) - 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 - ABELCET, AMBISOME = Lipid preparations that are likely as effective and much less toxic (esp renal toxicity), although more expensive. Nowadays, rarely use plain old ampho B. (Chanu Rhee MD, Last Update 4/2011)

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