Meta-analysis of nebulized amphotericin B to prevent or treat pulmonary aspergillosis in immunosuppressed animals.

OBJECTIVES: Pulmonary aspergillosis in immunosuppressed patients is associated with significant mortality and morbidity. We assessed the prophylactic and therapeutic effect of nebulized amphotericin B (AmB) on mortality of immunosuppressed animals with pulmonary aspergillosis in this meta-analysis.

METHODS: Literature search was based on MEDLINE (1966 to January 15, 2007), EMBASE, and Cochrane-Controlled Trials Register (2006 issue 4) databases. Only randomized-controlled studies comparing nebulized AmB with placebo on immunosuppressed animals were included. Two reviewers reviewed and extracted the data independently.

RESULTS: Eight studies including 839 immunosuppressed animals were considered. The overall mortality of the immunosuppressed animals with pulmonary aspergillosis treated with nebulized AmB was reduced (69.4% versus 87.7%, odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.08-0.19; P < 0.0001). The effect of nebulized AmB on mortality was more significant when the drug was administered as prophylaxis before the inoculation of Aspergillus fumigatus (OR 0.07, 95% CI: 0.03-0.12, P = 0.0001; I(2) = 0) than as a therapeutic agent (OR 0.20, 95% CI: 0.11-0.36, P < 0.0001; I(2) = 0) (ratio of the 2 ORs = 2.86, 95% CI: 1.03-6.11; P = 0.04). The effectiveness of AmB desoxycholate (OR 0.16, 0.06-0.38, P < 0.0001; I(2) = 0) and lipid-associated (liposomal, or lipid complex or colloidal dispersion) amphotericin (OR 0.11, 95% CI: 0.06-0.20, P < 0.0001; I(2) = 0) was not significantly different (ratio of the 2 ORs = 1.46, 95% CI: 0.49-4.39; P = 0.50). Three studies evaluated the potential side effects of nebulized amphotericin and showed that there was no significant renal toxicity but the amphotericin desoxycholate had some detrimental effects on pulmonary surfactant function.

CONCLUSIONS: The use of nebulized amphotericin, either as a prophylactic or therapeutic agent, is effective in reducing mortality of immunosuppressed animals with pulmonary aspergillosis. A large randomized controlled trial is needed to confirm whether combining nebulized amphotericin with systemic antifungal agents will reduce mortality in immunosuppressed patients with suspected or proven pulmonary aspergillosis.