ArticleThe Journal of infectious diseases2026
Can Fluconazole Be Used to Treat Non-Resistant Candida (Candidozyma) auris Infections? Preclinical Pharmacokinetic/Pharmacodynamic Data From a Galleria mellonella Infection Model.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAzole therapy is currently not used against Candida auris infections. Although fluconazole resistance is prevalent, 10% to 45% of isolates among clades remain non-resistant (minimum inhibitory concentrations [MICs] <32 mg/L). We evaluated fluconazole pharmacokinetics/pharmacodynamics against these isolates using a Galleria mellonella model.
methodsNine C. auris isolates representing 5 clades and MICs of 1 to 128 mg/L were studied, and 4 Candida albicans isolates were included for model validation. Larvae were infected with lethal inocula and treated for 4 days with human-equivalent fluconazole doses. Efficacy endpoints were 24-hour change in fungal burden and 7-day survival. Free-drug 24-hour area under the concentration-time curve divided by the MIC (fAUC0-24/MIC) target was derived by a sigmoidal Emax model, and Monte Carlo simulations estimated the probability of target attainment.
resultsFor C. albicans, the Clinical and Laboratory Standards Institute (CLSI) fAUC0-24/MIC corresponding to EI50 for 24-hour fungal burden reduction was 35.5, consistent with murine models. EI90 survival targets were 76.5 (CLSI) and 68.9 (European Committee on Antimicrobial Susceptibility Testing) fAUC0-24/MIC, supporting the clinical breakpoints and validating the model. For C. auris, EI90 targets for survival were 93.2 (CLSI) and 63.2 (European Committee on Antimicrobial Susceptibility Testing) fAUC0-24/MIC, and probabilities of target attainment >95% were found for isolates with MICs up to 2, 4, and 8 mg/L with fluconazole doses of 400, 800, and 1200 mg/d, respectively.
conclusionsFluconazole demonstrated similar in vivo activity against C. auris and C. albicans. Putative wild type isolates with MICs ≤8 mg/L may be treatable with 1200 mg/d. Clinical studies are needed to verify the efficacy of fluconazole against C. auris.
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