Antifungals — Azoles, Echinocandins & Amphotericin B

Also known as Azole · Fluconazole · Voriconazole · Posaconazole · Isavuconazole · Echinocandin · Caspofungin · Micafungin · Amphotericin B · Liposomal amphotericin · AmBisome · Flucytosine · Mucormycosis · Aspergillus

The antifungals comprise the three classes. The azoles (the fluconazole, the voriconazole, the posaconazole, the isavuconazole) inhibit the 14-alpha-demethylase, the block the ergosterol synthesis; the fluconazole for the Candida and the Cryptococcus, the voriconazole the Aspergillus first-line (the TDM, the visual disturbances), the posaconazole the mucormycosis, the isavuconazole the broad plus UNIQUE SHORTENS QT; the adverse the hepatotoxicity, the QT prolongation, the CYP3A4. The echinocandins (the caspofungin, the micafungin, the anidulafungin) inhibit the beta-1,3-glucan synthase, the cell-wall; the Candida (incl the fluconazole-resistant and the biofilm and the catheter), the low the toxicity and the low the interactions, the…

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The one-paragraph exam answer — antifungals in the ICU

Four classes, four cellular targets. The azoles (fluconazole, voriconazole, posaconazole, isavuconazole) starve the fungus of ergosterol by inhibiting 14-α-demethylase — fluconazole for Candida and Cryptococcus, voriconazole first-line for invasive aspergillosis (mandatory TDM, trough 1–5.5), posaconazole for mucormycosis and prophylaxis, isavuconazole broad and uniquely QT-shortening. The echinocandins (caspofungin, micafungin, anidulafungin) dissolve the β-1,3-glucan cell wall and are first-line for ICU candidaemia including fluconazole-resistant species — low toxicity, IV only. Amphotericin B binds ergosterol and punches a membrane pore — the broadest cover (Mucorales, Cryptococcus), but nephrotoxic, so use the lipid formulation. Flucytosine corrupts DNA and is used only with amphotericin for cryptococcal meningitis. By organism: Candida → echinocandin first; Aspergillus → voriconazole or isavuconazole; Mucor → amphotericin and the knife.^[1]^[10]

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[1]Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis N Engl J Med, 2002.PMID 12167683
[2]Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis N Engl J Med, 2002.PMID 12490683
[3]Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial Lancet, 2016.PMID 26684607
[4]Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis Lancet Infect Dis, 2016.PMID 26969258
[5]Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia N Engl J Med, 2007.PMID 17251531
[6]Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease N Engl J Med, 2007.PMID 17251530
[7]Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial Lancet, 2007.PMID 17482982
[8]Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis N Engl J Med, 2007.PMID 17568028
[9]Pappas PG, Rotstein CM, Betts RF, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis Clin Infect Dis, 2007.PMID 17806055
[10]Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America Clin Infect Dis, 2016.PMID 26679628
[12]Saag MS, Graybill RJ, Larsen RA, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America Clin Infect Dis, 2000.PMID 10770733
[13]Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute N Engl J Med, 1994.PMID 7935701
[14]Brouwer AE, Rajanuwong A, Chierakul W, Griffin GE, Larsen RA, White NJ, Harrison TS Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial Lancet, 2004.PMID 15172774
[15]Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa N Engl J Med, 2018.PMID 29539274
[16]Cornely OA, Bassetti M, Calandra T, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients Clin Microbiol Infect, 2012.PMID 23137135
[17]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium Lancet Infect Dis, 2019.PMID 31699664
[18]Jeong W, Keighley C, Wolfe R, et al. Contemporary management and clinical outcomes of mucormycosis: a systematic review and meta-analysis of case reports Int J Antimicrob Agents, 2019.PMID 30639526
[19]Lee J, Ng P, Hamandi B, et al. Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review Ann Pharmacother, 2021.PMID 32772568
[20]Kim SH, Lee DG, Kwon JC, et al. Clinical Impact of Cytochrome P450 2C19 Genotype on the Treatment of Invasive Aspergillosis under Routine Therapeutic Drug Monitoring of Voriconazole in a Korean Population Infect Chemother, 2013.PMID 24475354
[21]Keirns J, Desai A, Kowalski D, et al. QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization Clin Pharmacol Ther, 2017.PMID 28074556
[22]Ueda T, Takesue Y, Tokimatsu I, et al. The incidence of endophthalmitis or macular involvement and the necessity of a routine ophthalmic examination in patients with candidemia PLoS One, 2019.PMID 31120928
[23]Nucci M, Braga PR, Nouér SA, et al. Time of catheter removal in candidemia and mortality Braz J Infect Dis, 2018.PMID 30468708
[24]León C, Ruiz-Santana S, Saavedra P, et al. A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization Crit Care Med, 2006.PMID 16505659
[25]Cagnoni PJ Liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients J Antimicrob Chemother, 2002.PMID 11801587
[26]Gustot T, Ter Heine R, Brauns E, et al. Caspofungin dosage adjustments are not required for patients with Child-Pugh B or C cirrhosis J Antimicrob Chemother, 2018.PMID 29860319
[27]Liu P, Ruhnke M, Meersseman W, et al. Pharmacokinetics of anidulafungin in critically ill patients with candidemia/invasive candidiasis Antimicrob Agents Chemother, 2013.PMID 23335738
[28]Nett JE, Andes DR Antifungal Agents: Spectrum of Activity, Pharmacology, and Clinical Indications Infect Dis Clin North Am, 2016.PMID 26739608