3 years ago

Choosing optimal antifungal agents to prevent fungal infections in non-neutropenic critically ill patients: trial sequential analysis, network meta-analysis, and pharmacoeconomic analysis.

Wang, Xing, Li, Xie, Dong, Meng, Chen
The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed as well as the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that have compared untargeted antifungal treatments applied to non-neutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease all-cause mortality (odds ratio [OR]=0.89, 95% confidence interval [CI]=0.70--1.14), but it did reduce the incidence of proven IFI (OR=0.45, 95%CI=0.29--0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR=0.35, 95%CI=0.19--0.65). The incremental cost-effectiveness ratios per life-years saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention were US$ 889, US$ 9994 and US$ 10351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in non-neutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Fluconazole remains an only effective for IFI prevention and well-tolerated antifungals that is significantly cheaper than echinocandins.

Publisher URL: http://doi.org/10.1128/AAC.00620-17

DOI: 10.1128/AAC.00620-17

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