title: Effectiveness of systemic antifungal prophylaxis in patients with neutropenia after chemotherapy: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Invasive fungal infections are responsible for substantial morbidity and mortality among patients with neutropenia after chemotherapy.
  
  
  OBJECTIVE
  This meta-analysis was conducted to estimate the effect of systemic antifungal prophylaxis on the frequency of invasive fungal infections in patients with neutropenia and the mortality associated with these infections.
  
  
  METHODS
  MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through September 15, 2010, for English-language publications of randomized controlled trials that compared systemic antifungal prophylaxis with placebo or no treatment in patients with neutropenia. Studies involving nonsystemic antifungal agents, direct comparisons of antifungal agents, and empirical, preemptive, or salvage treatment were excluded. Data were extracted according to European Organization for Research and Treatment of Cancer definitions of proven, possible, or probable fungal infections. Effect measures were reported as odds ratios (ORs) for fungal infection and mortality. Outcomes were pooled using random-effects meta-analysis. Study quality was assessed based on the study setting (single center or multicenter), institutional review board approval/informed consent, randomization, description of allocation concealment, double blinding, and reporting of dropouts.
  
  
  RESULTS
  Twenty-six trials including a total of 3979 patients were included in the meta-analysis. Antifungal prophylaxis was associated with significant reductions in proven fungal infections (OR = 0.43; 95% CI, 0.31-0.60; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI, 0.30-0.80; NNT = 53). Overall mortality was not affected by antifungal prophylaxis (OR = 0.92; 95% CI, 0.74-1.14). Antifungal prophylaxis was associated with a reduction in risk for proven Candida infections (OR = 0.28; 95% CI, 0.20-0.38), but not for aspergillosis or zygomycosis. Antifungal prophylaxis was also associated with a decreased need for antifungal therapy (OR = 0.64; 95% CI, 0.48-0.86). In an explanatory subgroup analysis of major outcomes, only recipients of a hematopoietic stem cell transplant (HSCT) had a significant likelihood of benefiting from antifungal prophylaxis in terms of reductions in risk for proven infections (OR = 0.27; 95% CI, 0.16-0.44) and mortality attributed to infections (OR = 0.41; 95% CI, 0.21-0.81). A metaregression analysis indicated that a multicenter (vs single-center) design and a double-blind (vs unblinded) design were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections, respectively.
  
  
  CONCLUSIONS
  Systemic antifungal prophylaxis was associated with a reduction in proven fungal infections and mortality attributed to these infections in patients with neutropenia after chemotherapy. In the setting of HSCT, antifungal prophylaxis was associated with reductions in both proven infections and mortality attributed to infections. There was no significant association between antifungal prophylaxis and overall mortality.
authors.affiliation: Department of Pathophysiology, Medical School, University of Athens, Athens, Greece. pd.ziakas@gmail.com
authors.forename: Panayiotis D
authors.initials: PD
authors.lastname: Ziakas
authors.forename: Irene S
authors.initials: IS
authors.lastname: Kourbeti
authors.forename: Michael
authors.initials: M
authors.lastname: Voulgarelis
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009181:Mycoses / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D009503:Neutropenia / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents