Skip to main content
Journal cover image

Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations.

Publication ,  Journal Article
Alexander, BD; Johnson, MD; Pfeiffer, CD; Jiménez-Ortigosa, C; Catania, J; Booker, R; Castanheira, M; Messer, SA; Perlin, DS; Pfaller, MA
Published in: Clin Infect Dis
June 2013

BACKGROUND: Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations. METHODS: We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-2010) and correlated treatment outcome with minimum inhibitory concentration (MIC) results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungin) and FKS1 and FKS2 gene sequences were determined. RESULTS: Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19-58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence. CONCLUSIONS: Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

June 2013

Volume

56

Issue

12

Start / End Page

1724 / 1732

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Retrospective Studies
  • Mutation
  • Middle Aged
  • Microbiology
  • Microbial Sensitivity Tests
  • Membrane Proteins
  • Male
  • Infant, Newborn
  • Infant
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Alexander, B. D., Johnson, M. D., Pfeiffer, C. D., Jiménez-Ortigosa, C., Catania, J., Booker, R., … Pfaller, M. A. (2013). Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis, 56(12), 1724–1732. https://doi.org/10.1093/cid/cit136
Alexander, Barbara D., Melissa D. Johnson, Christopher D. Pfeiffer, Cristina Jiménez-Ortigosa, Jelena Catania, Rachel Booker, Mariana Castanheira, Shawn A. Messer, David S. Perlin, and Michael A. Pfaller. “Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations.Clin Infect Dis 56, no. 12 (June 2013): 1724–32. https://doi.org/10.1093/cid/cit136.
Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-Ortigosa C, Catania J, Booker R, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013 Jun;56(12):1724–32.
Alexander, Barbara D., et al. “Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations.Clin Infect Dis, vol. 56, no. 12, June 2013, pp. 1724–32. Pubmed, doi:10.1093/cid/cit136.
Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-Ortigosa C, Catania J, Booker R, Castanheira M, Messer SA, Perlin DS, Pfaller MA. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013 Jun;56(12):1724–1732.
Journal cover image

Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

June 2013

Volume

56

Issue

12

Start / End Page

1724 / 1732

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Retrospective Studies
  • Mutation
  • Middle Aged
  • Microbiology
  • Microbial Sensitivity Tests
  • Membrane Proteins
  • Male
  • Infant, Newborn
  • Infant