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Table 36 1 summarizes the major properties of currently available antifungal agents Several different lipid-based amphotericin B formulations are used to treat systemic candidiasis, invasive aspergillosis and other disseminated mold infections, disseminated histoplasmosis, and cryptococcal meningitis Their principal advantage appears to be substantially reduced nephrotoxicity, allowing administration of much higher doses Because of their expense, use of these agents should be reserved for individuals in whom significant nephrotoxicity develops during amphotericin B therapy Three agents of the echinocandin class, caspofungin acetate, anidulafungin, and micafungin sodium, are currently approved The echinocandins have relatively few adverse effects and are useful for the treatment of invasive Candida infections Caspofungin acetate is also approved for use in refractory cases of invasive aspergillosis Voriconazole has excellent activity against a broad range of fungal pathogens and has been FDA approved for use in invasive Aspergillus cases, Fusarium and Scedosporium infections, Candida esophagitis, deep Candida infections, and candidemia Posaconazole, a new azole, is available and has good activity against a broad range of filamentous fungi, including some of the

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Fungi previously considered to be harmless colonizers, including Pseudallescheria boydii (Scedosporium apiospermum), Scedosporium prolificans, Fusarium, Paecilomyces, Trichoderma longibrachiatium, and Trichosporon, are emerging as significant pathogens in immunocompromised patients This occurs most often in patients being treated for hematopoietic malignancies and in those receiving broad-spectrum antifungal prophylaxis Infection may be localized in the skin, lungs, or sinuses, or widespread disease may appear with lesions in multiple organs Colonization of old cavitary disease may cause minimal symptoms or may precede dissemination with meningitis or brain abscesses Endocarditis occurs more com-

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Joined: 19 Mar 2008. Location: United States Online Status: Offline Posts: 36, Quote snufse Reply bullet Topic: QR Codes Posted: 02 May 2012 ...

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Drug Amphotericin B Dosing 03 15 mg/kg/d intravenously Renal Clearance No CSF Penetration Poor Toxicities Rigors, fever, azotemia, hypokalemia, hypomagnesemia, renal tubular acidosis, anemia Fever, rigors, nausea, hypotension, anemia, azotemia, tachypnea Fever, rigors, nausea, hypotension, azotemia, anemia, tachypnea, chest tightness Diarrhea, hepatic enzyme elevations, histaminemediated reactions Transient neutropenia; hepatic enzyme elevations when used with cyclosporine Rash, rigors, headache, phlebitis Nausea, rash, alopecia, headache, hepatic enzyme elevations Leukopenia,2 rash, diarrhea, hepatitis, nausea, vomiting Nausea, hypokalemia, edema, hypertension Spectrum of Activity All major pathogens except Scedosporium

100 mg intravenous loading dose, followed by 50 mg/d intravenously in one dose 70 mg intravenous loading dose, followed by 50 mg/ d intravenously in one dose 150 mg intravenously in one dose (treatment) 50 mg (prophylaxis) 100 400 mg/d in one or two doses intravenously or orally 100 150 mg/kg/d orally in four divided doses 100 400 mg/d orally in one or two doses; 200 400 mg/d IV in one or two doses

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Aspergillosis, mucosal and invasive candidiasis, empiric antifungal therapy in febrile neutropenia Esophageal candidiasis, prophylaxis in hematopoietic stem cell transplantation Mucosal candidiasis (including urinary tract), cryptococcosis, histoplasmosis, coccidioidomycosis Cryptococcosis,3 candidiasis,3 chromomycosis Histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, mucosal candidiasis (except urinary), sporotrichosis, aspergillosis, chromomycosis Nonmeningeal histoplasmosis and coccidioidomycosis, blastomycosis, paracoccidioidomycosis, mucosal candidiasis (except urinary) Broad range of activity including zygomycosis Dermatophytes, sporotrichosis

Anorexia, nausea, suppression of testosterone and cortisol, rash, headache, hepatic enzyme elevations, hepatic failure Nausea, vomiting, abdominal pain, diarrhea, and headache Nausea, abdominal pain, taste disturbance, rash, diarrhea, and hepatic enzyme elevations Transient visual disturbances, rash, hepatic enzyme elevations4

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200 400 mg/d orally in two doses or 12 mg/kg intravenously as loading dose for 2 days followed by 6 mg/kg/d intravenously in two doses

No dosage adjustment required for renal insufficiency; dosage adjustment necessary with moderate to severe hepatic dysfunction Use should be monitored with blood levels to prevent this or the dose adjusted according to creatinine clearance 3 In combination with amphotericin B 4 Administration with drugs that are metabolized by the cytochrome P450 system is contraindicated or requires careful monitoring

Torres HA et al Posaconazole: a broad-spectrum triazole antifungal Lancet Infect Dis 2005 Dec;5(12):775 85 [PMID: 16310149] Vazquez JA et al Andiulafungin: a novel echinocandin Clin Infect Dis 2006 Jul 15;43(2):215 22 [PMID: 16779750]

zygomycetes Cytokine therapy (such as with interferon- ) and use of growth factors such as granulocyte macrophagecolony-stimulating factor (GM-CSF) (sargramostim or molgramostim) have been shown in animal models to increase clearance of fungi and result in better clinical outcomes and are being evaluated in human disease

Joseph JM et al Micafungin: a new echinocandin antifungal Pharmacotherapy 2007 Jan;27(1):53 67 [PMID: 17192162]

Specific information regarding amphotericin and caspofungin appears in CMDT Online at http://wwwaccessmedicinecom

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