ICU病房抗真菌经验性治疗

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.
Site of Action of Selected Anti-fungal Agents Cell membrane
Polyenes AmB (sterols) Azoles Fluconazole (CYP450)
Cell wall
Echinocandins Caspofungin (Glucan synthesis inhibitors)
• 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) – Caspofungin iv (liver toxicity)
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.
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
National Epidemiology of Mycosis Survey (NEMIS) was a prospective, multicenter study conducted at 6 US sites from 1993–1995 to examine rates of risk factors for the development of candidal bloodstream infections (CBSIs) among patients in surgical and neonatal intensive care units >48 hours. Among 4276 patients, 42 CBSIs occurred. Adapted from Blumberg HM et al, and the NEMIS Study Group Clin Infect Dis 2001;33:177–186; Garber G Drugs 2001; 61(suppl 1):1–12.
– 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.
• Echinocandins
• 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 hardwarБайду номын сангаас, immuno -suppresion, site of disease ex. urine.
Invasive Mycosis
Candidiasis
Aspergillosis
MICU or SICU
Oncology
SOT or BMT
Barrier immunity
Decreasing immunity
Barrier plus cellular immunity
Treatment of Invasive Mycosis