ArticleAntimicrobial agents and chemotherapy2012
Optimizing Echinocandin dosing and susceptibility breakpoint determination via in vivo pharmacodynamic evaluation against Candida glabrata with and without fks mutations.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 42 citations in OpenAlex.
- Clinical pharmacodynamic index identification for micafungin in esophageal candidiasis: dosing strategy optimization.Antimicrobial agents and chemotherapy · 2013Trial
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- Development of an in vitro pharmacokinetic/pharmacodynamic model in the presence of serum for studying micafungin activity against Candida albicans: a need for revision of CLSI susceptibility breakpoints.The Journal of antimicrobial chemotherapy · 2023Article
- Analysis of Candida Antifungal Resistance Using Animal Infection Models.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Pseudomonas Synergizes with Fluconazole againstInfection and immunity · 2022Article
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
- Amphotericin B Induction with Voriconazole Consolidation as Salvage Therapy forAntimicrobial agents and chemotherapy · 2019Article
- Glycyrrhizin Use for Multi-Drug Resistant Pseudomonas aeruginosa: In Vitro and In Vivo Studies.Investigative ophthalmology & visual science · 2019Article
- Fungal Resistance to Echinocandins and the MDR Phenomenon inJournal of fungi (Basel, Switzerland) · 2018Review
- Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation.Infection and drug resistance · 2018Review
- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Article
- Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection.Antimicrobial agents and chemotherapy · 2017Article
- Clinical perspectives on echinocandin resistance among Candida species.Current opinion in infectious diseases · 2015Review
- Dose escalation studies with caspofungin against Candida glabrata.Journal of medical microbiology · 2015Article
- Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model.Antimicrobial agents and chemotherapy · 2015Article
- Antifungal pharmacokinetics and pharmacodynamics.Cold Spring Harbor perspectives in medicine · 2014Review
- Use of anidulafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 4,290 clinical isolates of Candida by using CLSI methods and interpretive criteria.Journal of clinical microbiology · 2014Article
- In vitro antifungal susceptibility of Candida glabrata to caspofungin and the presence of FKS mutations correlate with treatment response in an immunocompromised murine model of invasive infection.Antimicrobial agents and chemotherapy · 2014Article
- Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria.Journal of clinical microbiology · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Echinocandins are a preferred therapy for invasive candidiasis due to their potency and broad spectrum. Resistance, especially in Candida glabrata, is an emerging threat to their use. Pharmacodynamic (PD) studies examining reduced susceptibility secondary to fks mutations in C. glabrata are lacking. The current study explored PD targets for anidulafungin, caspofungin, and micafungin in an in vivo invasive candidiasis model against 11 C. glabrata isolates with known or putative fks mutations. The PD targets were compared to those of 8 wild-type (WT) isolates. The MIC ranges in the WT group were 0.03 to 0.25 mg/liter for anidulafungin, 0.03 to 0.25 mg/liter for caspofungin, and 0.01 to 0.06 mg/liter for micafungin. The MIC ranges for mutants were 0.06 to 4, 0.25 to 16, and 0.13 to 8 mg/liter for the same compounds, respectively. The mean free drug 24-h area under the concentration-time curve (AUCf)/MIC ratio associated with a stasis endpoint for the WT group was 13.2 for anidulafungin, 2.04 for caspofungin, and 6.78 for micafungin. Comparative values for mutants were 3.43, 2.67, and 0.90, respectively. Pharmacokinetic data from patients suggest that the C. glabrata PD targets needed for success in this model could be achieved based on MIC values of 0.25 mg/liter for anidulafungin, 2 mg/liter for caspofungin, and 0.5 mg/liter for micafungin. These values are higher than recently identified epidemiology cutoff values (ECVs). The results suggest that drug-specific MIC breakpoints could be increased for caspofungin and micafungin against C. glabrata and could include organisms with mutations in fks-1 and fks-2. While identification of genetic mutants is epidemiologically important, the phenotype (MIC) provides a better predictor of therapeutic efficacy.
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