Weekly high-dose liposomal amphotericin B (L-AmB) in critically ill septic patients with multiple Candida colonization: The AmBiDex study.

BACKGROUND: To demonstrate the feasibility and safety of weekly high-dose liposomal amphotericin B (L-AmB) (as a pre-emptive antifungal treatment) for 2 weeks in patients with septic shock and Candida colonization. METHODS: Pilot, multicentre, open-label, prospective study conducted in seven French ICUs. Non-immunocompromised patients, receiving mechanical ventilation were eligible if they presented ICU-acquired severe sepsis requiring newly administered antibacterial agents and Candida colonization in at least two sites. Exclusion criteria included the need for antifungal therapy and creatinine > 220 mumol/L. All patients were to receive a high-dose L-AmB (10 mg/kg/week) for two weeks. A follow-up period of 21 days following the second administration of L-AmB was conducted. Treated patients were compared to 69 matched untreated controls admitted in the same ICUs before the study period. RESULTS: Twenty-one patients were included in the study, of which 20 received at least one infusion of high-dose L-AmB. A total of 24 adverse events were identified in 13(61%) patients. Fourteen adverse events were categorized as serious in 8(38%) patients. In four cases the adverse events were considered as potentially related to study drug administration and resulted in L-AmB discontinuation in one patient. Few patients experienced severe renal toxicity since no patient presented with severe hypokalemia. No patients required renal replacement therapy. Compared to matched controls, no significant increase in serum creatinine levels in patients receiving high-dose L-AmB was reported. CONCLUSIONS: Weekly administration of high-dose L-AmB has a manageable safety profile and is feasible in patients with ICU-acquired sepsis and multiple Candida colonization. Trials of L-AmB versus other antifungal agents used as pre-emptive antifungal therapy are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00697944.