Selectionofanoptimalantifungalfortreatmentofinvasive.pptVIP

Disclosures No disclosures to report Selection of an optimal antifungal for treatment of invasive aspergillosis: susceptibility/resistance, adverse reactions, drug interactions John Bennett, M.D. Choices for aspergillosis Polyene: liposomal (AmBisome), lipid complex (ABLC) Intravenous or oral azole: Voriconazole, Isavuconazole Intravenous echinocandin: caspofungin, micafungin? Oral only azole: posaconazole, itraconazole Issues in drug choice Can the patient take oral alimentation? How urgent is the need for Rx? Is the Aspergillus species known? Are drug interactions manageable? How tenuous is the patient’s renal function? How certain do we need to be that the drug is effective? Oral alimentation Posaconazole levels up 2.6 fold with nonfat food; 4 fold up with fatty meal Response improved with higher level Quartile C av Improved with posa of blood level (ng/ml) 1 124 24% (4/17) 2 411 53% (9/17) 3 719 53% (9/17) 4 1250 75% (12/16) Walsh, CID 2007:44:2-12 Urgency: time to steady state Posaconazole: 5-7 days to steady state. Loading not possible. Itraconazole: IV no longer available. Oral loading over 3 days. Voriconazole, echinocandins, ampho B: loading in 24 hrs or less Ampho B resistance in Aspergillus terreus 3-5% isolates are A. terreus Walsh JID 2003: Exp infection response to ampho poor Steinbach, AAC 2004: Am B MIC 4X higher Hachem, Cancer 2004: 28% response to ampho with A. terreus, 39% with A. fumigatus Lass-Fl?rl, Brit J Hem 2005: compared 32 pts with A. terreus vs 35 with other Asp species: Infection more often disseminated (63% vs 32%) and poorer response to ampho 21% vs 46% DRUG-DRUG INTERACTIONS Voriconazole has many interactions, posaconazole slightly less Blood levels of many drugs increased Azole levels down with rifampin, rifabutin, efavirenz, Tegretol, phenytoin, other Echinocandin interactions with other drugs not significant though caspo levels down 30% with rifampin Renal function and antifungals Liposomal amph