ICU病房抗真菌验性治疗.ppt

Empiric Antifungal Therapy in the ICU Ramzi Moufarrej, M.D Chief of Critical Care Zayed Military Hospital / Abu Dhabi Introduction Invasive fungal infections have increased significantly over the last 2 decades. aging population with life sustaining therapies like renal dialysis broad spectrum antimicrobial therapy and invasive medical devices bone marrow transplantation (BMT) solid organ transplantation (SOT) intensive chemotherapy for malignancies HIV/AIDS epidemic. Risk for Invasive Mycosis Non-Neutropenic related to barrier breakdown, change in colonization. Acute renal failure (RR 4.2) Parenteral nutrition with intralipid (RR 3.6) Prior surgery specially GI (RR 7.3) Indwelling central line ? Triple lumen (RR 5.4) Broad spectrum antibiotics Diabetes Burns Mechanical Ventilation Steroids Neutropenic related to above plus immune cell suppression and underlying malignancy. Severe immunosuppressive: BMT or SOT Invasive Mycosis Treatment of Invasive Mycosis Polyenes Amphotericin B (AmB) or Liposomal AmB (kidney toxicity) Azoles Fluconazole 400-800 mg/day (liver toxicity, CYP450) Voriconazole (liver toxicity, visual disturbances, CYP450) Posaconazole (liver toxicity, CYP450) Echinocandins Caspofungin iv (liver toxicity) Combination ex. AmB/ Fluconazole (liver, kidney toxicity) Choice of agents depends on whether the patient on previous azole prophylaxis, culture results, local fungal sensitivity, colonization, renal or liver disease, presence of drug-drug interactions, presence of hardware, immuno -suppresion, site of disease ex. urine. Site of Action of Selected Anti-fungal Agents Adapted from Andriole VT J Antimicrob Chemother 1999;44:151–162; Graybill JR et al Antimicrob Agents Chemother 1997;41:1775–1777; Groll AH, Walsh TJ Expert Opin Invest Drugs 2001;10(8):1545–1558. Focus on Candidiasis Invasive Candida infections: 4th most common nosocomial bloodstream infection in the USA with mortality approaching 40% in line related candidemia* Species of Ca