Liposomal amphotericin B in the treatment of severe fungal infections. Results of a clinical cohort trial

摘要

BACKGROUND: Activity and efficacy of liposomal amphotericin B have been established for the treatment of severe fungal infections. Nephrotoxic side effects, especially during prolonged administration, are regarded as a major disadvantage. In this study we examined the response rates and side effects, particularly nephrotoxicity, of treatment with liposomal amphotericin B in a large cohort of patients. PATIENTS AND METHODS: 406 patients treated with liposomal amphotericin B between January 1999 and August 2003 in participating German hospitals were included. Documentation included demographic and clinical data, reason for the treatment with liposomal amphotericin B, length of treatment, response to antifungal treatment and side effects. RESULTS: 42.4% of the 406 patients were females. Their ages ranged from 1 day to 77 years. 83 % of the patients had malignancies and 65.5 % had fever of unknown origin (FUO). Mean duration of treatment with liposomal amphotericin B was 20 +/- 20 days, at an average dose of 2.3 mg/kg/d. 209 patients (51.5 %) showed complete response (CR),105 patients (25.9 %) partial response (PR) and 51 (12.6 %) patients died during the observation. 80.0 % of patients with FUO showed complete or partial response of symptoms. Mean serum creatinine increased from 0.9 mg/kg before start of therapy with liposomal amphotericin B to 1.1 mg/kg during treatment. Side effects (common toxicity criteria > grade 1) occurred in 94 patients (23/2 %). Among these hypokalemia (6.2 %) and liver damage (5,2 %) were the most common. Nephrotoxicity was documented in 17 patients (4.2 %). CONCLUSION: Liposomal amphotericin B is a safe and efficacious antifungal drug in the treatment of severe invasive fungal infections and fever of unknown origin. Nephrotoxicity is usually not a limiting factor when using liposomal amphotericin B, if it is administered in approved dosage.