Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata
Open accessAbstract
The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 μg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 μg/ml and for which micafungin MICs were ≥0.25 μg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 μg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates), all of which contained an acquired mutation in fks1 or fks2. By comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant isolates of C. glabrata tested in 2001 to 2004. These data document the broad emergence of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata.
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The CDC/SENTRY antimicrobial surveillance program reported a rise from 0 to 11% in the fraction of fluconazole-resistant strains that were also less susceptible to echinocandins between the studies performed in 2001-2004 and 2006-2010.
“Similarly, the CDC/SENTRY antimicrobial surveillance program reported a rise from 0 to 11% in the fraction of fluconazole-resistant strains that were also less susceptible to echinocandins between the studies performed in 2001–2004 and 2006–2010 [47].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [47]
A CDC/SENTRY study found that none of the fluconazole-resistant C. glabrata isolates from 2001 to 2004 demonstrated echinocandin resistance, while 11% of fluconazole-resistant isolates from 2006 to 2010 were also resistant to an echinocandin.
“A CDC/SENTRY Antimicrobial Surveillance Program study found that while none of the fluconazole-resistant C. glabrata isolates from 2001 to 2004 demonstrated echinocandin resistance, 11% of fluconazole-resistant isolates from 2006 to 2010 were also resistant to an echinocandin (Pfaller et al., 2012).”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Pfaller et al., 2012
Resistance to multiple antifungal classes (MDR) has been reported most frequently in C. glabrata.
“Resistance to multiple antifungal classes, or multidrug resistance (MDR), has been reported most frequently in this fungus (Pfaller et al., 2012).”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Pfaller et al., 2012
Reports of echinocandin resistance in patients with infections due to C. albicans, C. glabrata, C. tropicalis, and C. krusei are rising.
“However, reports of echinocandin resistance in patients with infections due to C. albicans, C. glabrata, C. tropicalis, and C. krusei are rising [111–116].”
From <i>Candida</i>Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [116]
Signs of multidrug resistance amongst azoles and echinocandins have already been described.
“The use of echinocandins and development of cross-resistance is creating apprehension, for the signs of multidrug resistance amongst azoles and echinocandins have already been described [168,169,170].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [169]
11.1%-58.3% of C. glabrata isolates resistant to echinocandins had cross resistance against fluconazole or other azoles.
“As a result, 11.1%–58.3% of C. glabrata isolates resistant to echinocandins had cross resistance against fluconazole or other azoles [168,169,172]”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [169]
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References 61 · Cited by 377
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- [3]3. Castanheira M, et al. 2010. Low prevalence of fks1 hotspot 1 mutations in a worldwide collection of Candida spp. Antimicrob. Agents Chemother. 54:2655–2659 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9]9. Clinical and Laboratory Standards Institute 2008. M27–S3 Reference method for broth dilution antifungal susceptibility testing of yeasts, 3rd informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA [Google Scholar]
- [12]12. Daneman N, et al. 2006. The emergence of caspofungin resistance during treatment of recurrent Candida glabrata candidaemia, abstr. P1204. 16th Eur. Congr. Clin. Microbiol. Infect. Dis.,, Nice, France, 1 to 4 April 2006 [Google Scholar]
- [13]13. Dodgson KJ, et al. 2005. Caspofungin resistant C. glabrata. Clin. Microbiol. Infect. 11(Suppl 2):364 [Google Scholar]
- [43]43. Pfaller MA, Diekema DJ. 2007. Azole antifungal drug cross-resistance: mechanisms, epidemiology, and clinical significance. J. Invasive Fungal Infect. 1:74–92 [Google Scholar]
- Authors
- Pfaller, M. A., Castanheira, M., Lockhart, S. R., Ahlquist, A. M., Messer, S. A., & Jones, R. N.
- Affiliations
- JMI Laboratories (US)
- Centers for Disease Control and Prevention (US)
- Tufts University (US)
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2012-04
- Volume
- 50
- Issue
- 4
- Pages
- 1199-1203
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC3318516
- OpenAlex
- W1972692992
- Cited by
- 377
- References
- 61
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 20 · 2023: 21 · 2022: 11 · 2021: 16 · 2020: 24 · 2019: 29 · 2018: 26 · 2017: 37 · 2016: 32 · 2015: 52 · 2014: 44 · 2013: 25 · 2012: 19
- FWCI
- 31.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- Candida glabrata, echinocandin resistance, fluconazole resistance, bloodstream infection, antifungal resistance, voriconazole, anidulafungin, caspofungin, micafungin, FKS1 mutations
- MeSH terms
- Adult, Aged, Antifungal Agents, Female, Fungal Proteins, Glucosyltransferases, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Fluconazole, Sentinel Surveillance, Mutation, Missense, Drug Resistance, Multiple, Fungal, Candida glabrata, Echinocandins, Young Adult, Candidemia
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