Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis

Ken Chen,Long Ge,Roy A Pleasants,Wei Liu,Kangning Peng,Suodi Zhai,Qi Wang

doi:10.1186/s12879-017-2263-6

Abstract

BackgroundThe most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.MethodsPubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.ResultsSeventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10–1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.ConclusionsOur results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.

Highlights

The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial
We aimed to evaluate the relative effectiveness of antifungal agents as empiric therapy in febrile neutropenic (FN) patients for all-cause mortality, fungal infectionrelated mortality, and treatment response via pairwise and network meta-analysis
Treatment response was principally defined as absence of IFDs, completion of therapy, fever resolution, and survival during the follow-up period

Summary

Introduction

The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Invasive fungal diseases (IFDs) are crucial causes of morbidity and mortality among febrile neutropenic (FN) patients after intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) as well as in other immunocompromised populations [1–3]. Cases of probable IFDs require a host factor, clinical features, and. Possible IFDs include cases with appropriate host factors and sufficient clinical evidence but no mycological support. These definitions have been adopted by most practice guidelines for IFDs. The most commonly identified fungal species associated with IFD are Candida species, Aspergillus, Cryptococcus and Pneumocystis [9]

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