Empirical antifungal therapy in febrile neutropenic patients – systematic review

Abstract number: 1733_461

Goldberg E., Gafter-Gvili A., Paul M., Robenshtok E., Vidal L., Leibovici L.

Objectives: The practice of administering empirical antifungal therapy to persistently febrile neutropenic patients has become a standard of care. This study aims to evaluate if empiric antifungal treatment reduces mortality and prevents invasive fungal infections (IFI).

Methods: Systematic review and meta-analysis including randomised controlled trials (RCTs) comparing empirical antifungal treatment with placebo or no intervention (control), or another regimen, in persistently neutropenic patients. Search was conducted until 2006. Outcomes assessed were: All-cause mortality, documented IFI, fungal-related mortality, composite failure, invasive mould infections, invasive yeast infections, resolution of fever during neutropenia, adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled.

Results: Our search yielded 25 trials, 5 of which compared polyenes or azoles to control, and 20 compared between different regimens of polyenes, azoles or glucan synthesis inhibitors. Compared to control, there was no difference in all-cause mortality (RR 0.93; 95% CI 0.55–1.58, 5 trials, Fig.1).The risk for developing documented IFI was lower (RR 0.30; 95% CI 0.11–0.84, 4 trials, 4 events in the treatment group versus 15 in the control). When azoles (fluconazole, ketoconazole, itraconazole, voriconazole) were compared to polyenes (amphotericin B in 7 trials, liposomal ampho B in 1 trial) there was a trend in favour of azoles for decreased all-cause mortality (RR 0.88; 95% CI 0.71–1.08, 8 trials) and for decreased documented IFI (RR 0.67; 95% CI 0.44–1.02, 7 trials). Adverse events which required discontinuation were less frequent in the azole group (RR 0.52; 95% CI 0.39–0.69, 6 trials).

Conclusions: Our review demonstrates that empirical antifungal therapy does not reduce mortality. Although it reduces IFI, data are based on a small number of trials and events. Future trials should pursue a pre-emptive approach using improved diagnostic tools (such as galactomannan testing, high resolution CT), to identify the patients for whom antifungal treatment is warranted. The use of amphotericin B as empirical therapy seems unwarranted since it appears to be less effective than azoles, with no mortality benefit and an increased rate of side effects

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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