ArticleAntimicrobial agents and chemotherapy2012
The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata.
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99 citing papers in PubMed, 170 citations in OpenAlex.
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- Prevalence and molecular basis of resistance to echinocandins among clinical Candida glabrata isolates in Guangdong province, China.BMC microbiology · 2025Article
- Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.Acta pharmaceutica Sinica. B · 2025Review
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- Comparative evaluation of antifungal susceptibility testing methods of invasive Candida species and detection of FKS genes mutations in caspofungin intermediate and resistant isolates.BMC infectious diseases · 2025Article
- Drug analysis of a fatal case of bloodstream infection combined with urinary tract infection due to echinocandin-resistantIDCases · 2025Article
- Climatic and endothermic thermal stress adaptation may be a major driver of emerging and emergent multidrug resistant fungi.Frontiers in microbiology · 2025Review
- Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.PLoS pathogens · 2024Article
- Fighting Emerging Caspofungin-ResistantAntibiotics (Basel, Switzerland) · 2024Article
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- Macrophage internalization creates a multidrug-tolerant fungal persister reservoir and facilitates the emergence of drug resistance.Nature communications · 2023Article
- The challenges of the genome-based identification of antifungal resistance in the clinical routine.Frontiers in microbiology · 2023Article
- Tackling the emerging threat of antifungal resistance to human health.Nature reviews. Microbiology · 2022Review
- Clinical utility of antifungal susceptibility testing.JAC-antimicrobial resistance · 2022Review
- Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations.Antimicrobial agents and chemotherapy · 2022Article
- Raman Spectroscopy of OralInternational journal of molecular sciences · 2022Article
39 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 2 countries.
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Abstract
Echinocandins are frontline agents against invasive candidiasis (IC), but predictors for echinocandin therapeutic failure have not been well defined. Mutations in Candida FKS genes, which encode the enzyme targeted by echinocandins, result in elevated MICs and have been linked to therapeutic failures. In this study, echinocandin MICs by broth microdilution and FKS1 and FKS2 mutations among C. glabrata isolates recovered from patients with IC at our center were correlated retrospectively with echinocandin therapeutic responses. Thirty-five patients with candidemia and 4 with intra-abdominal abscesses were included, 92% (36/39) of whom received caspofungin. Twenty-six percent (10) and 74% (29) failed and responded to echinocandin therapy, respectively. Caspofungin, anidulafungin, and micafungin MICs ranged from 0.5 to 8, 0.03 to 1, and 0.015 to 0.5 μg/ml, respectively. FKS mutations were detected in 18% (7/39) of C. glabrata isolates (FKS1, n = 2; FKS2, n = 5). Median caspofungin and anidulafungin MICs were higher for patients who failed therapy (P = 0.04 and 0.006, respectively). By receiver operating characteristic (ROC) analyses, MIC cutoffs that best predicted failure were >0.5 (caspofungin), >0.06 (anidulafungin), and >0.03 μg/ml (micafungin), for which sensitivity/specificity were 60%/86%, 50%/97%, and 40%/90%, respectively. Sensitivity/specificity of an FKS mutation in predicting failure were 60%/97%. By univariate analysis, recent gastrointestinal surgery, prior echinocandin exposure, anidulafungin MIC of >0.06 μg/ml, caspofungin MIC of >0.5 μg/ml, and an FKS mutation were significantly associated with failure. The presence of an FKS mutation was the only independent risk factor by multivariate analysis (P = 0.002). In conclusion, detection of C. glabrata FKS mutations was superior to MICs in predicting echinocandin therapeutic responses among patients with IC.
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