Evaluation and Management of Fever in the Neutropenic Patient 2003文档.pptVIP

Itraconazole for Empiric Therapy in Febrile Neutropenia Important considerations in this study Ampho B dose was 0.7-1.0 mg/kg/d oral itraconazole could be substituted for IV as early as 7 days, but typically on d 15 (levels OK) Rx continued until defervescence AND ANC 500 x 2d Boogaerts, et al. Ann Int Med, 2001;135:412-22 Effective level 250 mg/mL Glucan Synthase InhbitorsActivity Against Common and Uncommon Fungi Active Mod Activity Poor Activity Candida spp. H. capsulatum C. neoformans Aspergillus spp. C. imitis Fusarium spp. P. carinii B. dermatidis P. boydii S. schenckii Rhizopus spp. Alternaria spp. MICs 0.03-2.0 mg/mL 0.06-16 mg/mL 16-64 mg/mL Data are from Merck, on file and J Antibiot, 2000;53:1175-81 CaspofunginCancidas? IV infusion (over 1 hour); 70 mg load then 50 mg/d Half-life of 9-11 hours (second g-phase of 40-50 hours) Metabolized by slow hydrolysis and acetylation, and via spontaneous degradation excreted in in urine and feces No dose adjustment for renal failure Dose adjust for moderate hepatic failure, no experience in severe liver disease Caspofungin Empiric Therapy in Febrile Neutropenia* RCT Caspofungin 70/50 qd (n=564) Liposomal Ampho B 3 mg/kg/d (n=547) Five criteria of ‘success’ Successful Rx of baseline fungal infxn Absence of breakthrough fungal infxn Survival for at least 7 d after completion of drug Absence of w/d due to study drug-related toxicity Resolution of fever during neutropenia *Walsh, et al. ICAAC, Chicago, 2003 Voriconazole New triazole Structure much more like fluconazole than ketoconazole or itraconazole, thus, very bioavailable orally, but hepatic metabolism (CYP2C9 and CYP3A4) and much higher protein binding, shorter T1/2 (6 h) Fungistatic Activity against Candida (including C. kruseii and C. glabrata) and Aspergillus spp., but also against Crypto, Histo, Cocci, Blasto, and some ‘oddball’ fungi (P. boydii, some Fusarium spp.) VoriconazoleEmpiric Therapy in Febrile/Neutropenia* 837 Pts 73 centers; vs. l