A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations

• Published in: Clinical Therapeutics 2003-05, Vol.25 (5), p.1295-1320
• Main Authors: Barrett, Jane P., Vardulaki, Katerina A., Conlon, Christopher, Cooke, Jonathan, Daza-Ramirez, Pascual, Evans, E.Glyn V., Hawkey, Peter M., Herbrecht, Raoul, Marks, David I., Moraleda, Jose M., Park, Gilbert R., Senn, Stephen J., Viscoli, Claudio
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Amphotericin B - administration & dosage; Amphotericin B - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - administration & dosage; Antifungal Agents - therapeutic use; Antimicrobial agents; Biological and medical sciences; Bone marrow; Chemistry, Pharmaceutical; Chemotherapy; Disease prevention; Fungal infections; Handbooks; Health services; Humans; lipid-based amphotericin B; Lipids; Liver transplants; Medical sciences; Meningitis; meta-analysis; mortality; Mycoses - drug therapy; Mycoses - mortality; Neutropenia; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Stem cell transplantation; systematic review; Treatment Outcome
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(03)80125-X

Objective: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. Methods: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom ∗, lipid ∗, colloid ∗, antifungal agents , and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. Results: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. Conclusions: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.