Ziakas, P.D., Kourbeti, I.S., Voulgarelis, M., & Mylonakis, E. (2010). Effectiveness of systemic antifungal prophylaxis in patients with neutropenia after chemotherapy: a meta-analysis of randomized controlled trials. Clinical Therapeutics, 32, 2316–2336.doi: 10.1016/j.clinthera.2011.01.009
To estimate the impact of antifungal prophylaxis on the occurrence of proven systemic fungal infections in patients with neutropenia and to quantify its effect on mortality attributed to these infections.
A total of 11,418 references were retrieved.
A meta-analysis method of study was used. In specific, statistical analysis was performed to compare study results, including effects of antifungal prophylaxis using random effects and reported as pooled odds ratios (ORs) and 95% confidence intervals (CIs) using the Robins-Breslow-Greenland formula. For study cells with zero events, an ad hoc treatment arm continuity correction was used. Findings in which the 95% CI crossed 1 were not considered statistically significant. Statistical heterogeneity was assessed using the I2 statistic and Cochrane Q test. The Petro method was used for sensitivity analysis, and the Harbord modification of the Egger test was used to evaluate small study effects for major outcomes.
Patients were undergoing the active treatment phase of care.
Antifungal prophylaxis was associated with statistically significant reductions in proven fungal infections (OR = 0.43; 95% CI [0.31, 0.6]; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI [0.3, 0.8]; NNT = 53), reduction in risk for proven candida infections (OR = 0.28; 95% CI [0.2, 0.38]), and a decreased need for antifungal therapy (OR = 0.64; 95% CI [0.48, 0.86]). Explanatory subanalysis of major outcomes showed a reduced risk for proven infections among HSCT recipients only (OR = 0.27; 95% CI [0.16, 0.44]) and infection-related mortality (OR = 0.41; 95% CI [0.21, 0.81]). Not statistically significant were overall mortality (OR = 0.92; 95% CI [0.74, 1.14]) or reduction of aspergillosis or zygomycosis. Meta-regression analysis showed that multi-center and double-blind designs were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections.
Systemic antifungal prophylaxis was associated with decreased proven fungal infections and fungal infection-related mortality in patients with neutropenia following chemotherapy. Antifungal prophylaxis was also associated with decreased proven infections and infection-related mortality in HSCT recipients. Overall mortality was not improved through the use of antifungal prophylactic therapy.
The use of prophylactic antifungal therapy should be considered for patients receiving neutropenic-inducing chemotherapy and/or those undergoing HSCT.