title: A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations.
abstract: 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  The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases.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.
authors.affiliation: Jane Barrett Teaching and Consultancy, Cambridge, UK
authors.forename: Jane P
authors.initials: JP
authors.lastname: Barrett
authors.forename: Katerina A
authors.initials: KA
authors.lastname: Vardulaki
authors.forename: Christopher
authors.initials: C
authors.lastname: Conlon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cooke
authors.forename: Pascual
authors.initials: P
authors.lastname: Daza-Ramirez
authors.forename: E Glyn V
authors.initials: EG
authors.lastname: Evans
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hawkey
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Park
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Senn
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B