A correction for this article has been published in Annals of Clinical Microbiology and Antimicrobials 2009, 8:25

Research

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis

Edward J Mills^1,2 , Dan Perri³ , Curtis Cooper⁴ , Jean B Nachega^5,6 , Ping Wu² , Imad Tleyjeh^7,8 and Peter Phillips⁹

¹  Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada

²  Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada

³  Department of Medicine, McMaster University, Hamilton, Canada

⁴  Division of Infectious Diseases, Ottawa Hospital, University of Ottawa, Ottawa, Canada

⁵  Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

⁶  Department of Medicine and Centre for Infectious Diseases, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa

⁷  Division of Infectious Diseases, Department of Medicine, Research Center, King Fahd Medical City, Riyadh, Saudi Arabia

⁸  Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA

⁹  Division of Infectious Diseases, University of British Columbia, Vancouver, Canada

author email corresponding author email

Annals of Clinical Microbiology and Antimicrobials 2009, 8:23doi:10.1186/1476-0711-8-23

Published:	26 June 2009

Abstract

Objectives

Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.

Methods

We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses 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 of global 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 echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99–1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06–1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74–1.05, P = 0.17, I² = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84–1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48–1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin 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.