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

BMC Infectious Diseases

Thomas J Walsh⁵  Pinaki Biswas¹  Arlene L Reisman⁴  Haran T Schlamm⁶  Daniel H Kett⁷  Peter G Pappas⁸  Coleman Rotstein⁹  Andrew F Shorr²  Annette C Reboli³ 

[1] Pfizer Specialty Care (Statistics), Pfizer Inc, Collegeville, Pennsylvania, PA, USA;Pulmonary Critical Care Section, Washington Hospital Center, Washington, DC, USA;Division of Infectious Diseases, Cooper Medical School of Rowan University, 2 Aquarium Drive, Suite 305, Camden, NJ, 08103 USA;Pfizer Specialty Care (Statistics), Pfizer Inc, New York, NY, USA;Division of Infectious Diseases, Weill Cornell Medical College of Cornell University and New York Presbyterian Hospital, New York, NY, USA;Pfizer Specialty Care (Anti-Infectives), Pfizer Inc, New York, NY, USA;Department of Clinical Medicine, University of Miami Miller School of Medicine, Miami, FL, USA;Mycoses Study Group Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA;Division of Infectious Diseases, University of Toronto University Health Network, Toronto, ON, Canada

关键词: survival;    safety;    efficacy;    Candida;    echinocandins;   

Others  :  1175588
DOI  :  10.1186/1471-2334-11-261

 received in 2011-04-01, accepted in 2011-09-30,  发布年份 2011

【 摘 要 】

Background

Candida 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.

Methods

Global 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.

Results

In 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.

Conclusions

In 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 registration

ClinicalTrials.gov: NCT00058682

【 授权许可】

   
2011 Reboli et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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