Journal Article

FKS Mutant Candida glabrata: Risk Factors and Outcomes in Patients With Candidemia

Lasco, Todd M., Beyda, Nicholas D., Garey, Kevin W., Kilic, Abdullah, John, Julie, Alam, Mohammad J.

2014

Overview

Background. Echinocandins are recommended for Candia glabrata candidemia. Mutations in the FKS1 and FKS2 genes are associated with echinocandin resistance. Few studies have assessed risk factors for FKS mutant isolates and outcomes in patients receiving micafungin treatment. Methods. Patients with C. glabrata bloodstream infection admitted to a large, tertiary care hospital between 2009 and 2012 were included in this study. For each isolate, FKS1 and FKS2 genes were sequenced to identify mutations. Risk factors for FKS mutations and treatment outcomes in patients receiving an echinocandin were assessed using multivariate logistic regression. Results. Seventy-two patients were included in the study of which 13 (18%) had an FKS mutant isolate. The only significant predictor for FKS mutations was prior echinocandin exposure (odds ratio [OR], 19.9; 95% confidence interval [CI], 4.7–84.7; P ≤ .01). Treatment failure occurred in 17 (30%) of 57 patients who received an echinocandin and was more common in patients with FKS mutants (6 of 10; 60%) compared with non-FKS mutants (11 of 47; 23%). Underlying gastrointestinal disorder (OR, 4.7; 95% CI, 1.1–20.9; P = .04) and prior echinocandin exposure (OR, 8.3; 95% CI, 1.7–40.4; P ≤ .01) were independent predictors of echinocandin treatment failure. Treatment response and echinocandin minimum inhibitory concentrations varied among specific FKS mutations. Conclusions. FKS mutations were identified in 18% of 72 patients with C. glabrata candidemia. Common risk factors for FKS mutant isolates included previous echinocandin exposure, which also influenced response rates.

• Publisher: OXFORD UNIVERSITY PRESS,Oxford University Press
• Subject: Adult / Aged / Aged, 80 and over / Antifungal Agents - pharmacology / Antifungal Agents - therapeutic use / ARTICLES AND COMMENTARIES / Bacteria / Biological and medical sciences / Candida glabrata / Candida glabrata - drug effects / Candida glabrata - genetics / Candidemia / Candidiasis - diagnosis / Candidiasis - drug therapy / Candidiasis - microbiology / Central venous catheterization / Drug Resistance, Fungal - genetics / Echinocandins - pharmacology / Echinocandins - therapeutic use / Female / Fungal Proteins - genetics / Genetic mutation / Health outcomes / Human mycoses / Humans / Infectious diseases / Lipopeptides - pharmacology / Lipopeptides - therapeutic use / Male / Medical sciences / Medical treatment / Medical treatment failures / Microbial Sensitivity Tests / Middle Aged / Mutants / Mutation / Mycoses / Mycotic sepsis / Operating rooms / P values / Patient Outcome Assessment / Predisposing factors / Prognosis / Regression analysis / Risk assessment / Risk Factors / Treatment Failure / Treatment Outcome / Young Adult