Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcomeReport as inadecuate




Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome - Download this document for free, or read online. Document in PDF available to download.

BMC Infectious Diseases

, 11:261

Bacterial and fungal diseases

Abstract

BackgroundCandida albicans is the most common cause of candidemia and other forms of invasive candidiasis. Systemic infections due to C. albicans exhibit good susceptibility to fluconazole and echinocandins. However, the echinocandin anidulafungin was recently demonstrated to be more effective than fluconazole for systemic Candida infections in a randomized, double-blind trial among 245 patients. In that trial, most infections were caused by C. albicans, and all respective isolates were susceptible to randomized study drug. We sought to better understand the factors associated with the enhanced efficacy of anidulafungin and hypothesized that intrinsic properties of the antifungal agents contributed to the treatment differences.

MethodsGlobal responses at end of intravenous study treatment in patients with C. albicans infection were compared post-hoc. Multivariate logistic regression analyses were performed to predict response and to adjust for differences in independent baseline characteristics. Analyses focused on time to negative blood cultures, persistent infection at end of intravenous study treatment, and 6-week survival.

ResultsIn total, 135 patients with C. albicans infections were identified. Among these, baseline APACHE II scores were similar between treatment arms. In these patients, global response was significantly better for anidulafungin than fluconazole 81.1% vs 62.3%; 95% confidence interval CI for difference, 3.7-33.9. After adjusting for baseline characteristics, the odds ratio for global response was 2.36 95% CI, 1.06-5.25. Study treatment and APACHE II score were significant predictors of outcome. The most predictive logistic regression model found that the odds ratio for study treatment was 2.60 95% CI, 1.14-5.91 in favor of anidulafungin, and the odds ratio for APACHE II score was 0.935 95% CI, 0.885-0.987, with poorer responses associated with higher baseline APACHE II scores. Anidulafungin was associated with significantly faster clearance of blood cultures log-rank p < 0.05 and significantly fewer persistent infections 2.7% vs 13.1%; p < 0.05. Survival through 6 weeks did not differ between treatment groups.

ConclusionsIn patients with C. albicans infection, anidulafungin was more effective than fluconazole, with more rapid clearance of positive blood cultures. This suggests that the fungicidal activity of echinocandins may have important clinical implications.

Trial registrationClinicalTrials.gov: NCT00058682

Keywordsechinocandins Candida efficacy safety survival AbbreviationsAPACHEAcute Physiology and Chronic Health Evaluation

CIconfidence interval

IDSAInfectious Diseases Society of America

IVintravenous

MICsminimum inhibitory concentrations

mITTmodified intention-to-treat

SDstandard deviation.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2334-11-261 contains supplementary material, which is available to authorized users.

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Author: Annette C Reboli - Andrew F Shorr - Coleman Rotstein - Peter G Pappas - Daniel H Kett - Haran T Schlamm - Arlene L Re

Source: https://link.springer.com/







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