Antifungal Treatment for Invasive Candida Infections: A Mixed Treatment Comparison Meta-Analysis

Objectives:Invasive fungal infections are a major cause of mortality among patients at risk. Treatmentguidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungaltherapies on global response rates, mortality and safety.Methods:We searched independently and in duplicate 10 electronic databases from inception to May2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases ofinvasive candidiasis among predominantly adult populations. We performed a meta-analysis and thenconducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivityanalyses included dosage forms of amphotericin B and fluconazole compared to other azoles.Results:Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis ofglobal response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95%Confidence Interval [CI], 0.78–0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandinsversus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99–1.23, P = 0.08). One study comparedanidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06–1.51) in favor of anidulafungin. Wepooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of0.88 (95% CI, 0.74–1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for allcausemortality resulted in a pooled RR of 1.01 (95% CI, 0.84–1.20, P = 0.93). Anidulafungin versusfluconazole resulted in a RR of 0.73 (95% CI, 0.48–1.10, P = 0.34). Our mixed treatment comparisonanalysis found similar within-class effects across all interventions. Adverse event profiles differed, withamphotericin B exhibiting larger adverse event effects.Conclusion:Treatment options appear to offer preferential effects on response rates and mortality.When mycologic data are available, therapy should be tailored.