ArticleThe Journal of infectious diseases2024
Defining Optimal Doses of Liposomal Amphotericin B Against Candida auris: Data From an In Vitro Pharmacokinetic/Pharmacodynamic Model.
Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103.Nature microbiology · 2026Article
- Bad to the bone:ASM case reports · 2025Article
- Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.Current drug targets · 2025Review
- Comparative pharmacodynamics and dose optimization of liposomal amphotericin B againstAntimicrobial agents and chemotherapy · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCandida auris isolates exhibit elevated amphotericin B (AMB) minimum inhibitory concentrations (MICs). As liposomal AMB (L-AMB) can be safely administered at high doses, we explored L-AMB pharmacodynamics against C. auris isolates in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) dilution model.
methodsFour C. auris isolates with Clinical and Laboratory Standards Institute (CLSI) AMB MICs = 0.5-2 mg/L were tested in an in vitro PK/PD model simulating L-AMB pharmacokinetics. The in vitro model was validated using a Candida albicans isolate tested in animals. The peak concentration (Cmax)/MIC versus log10 colony-forming units (CFU)/mL reduction from the initial inoculum was analyzed with the sigmoidal model with variable slope (Emax model). Monte Carlo analysis was performed for the standard (3 mg/kg) and higher (5 mg/kg) L-AMB doses.
resultsThe in vitro PK/PD relationship Cmax/MIC versus log10 CFU/mL reduction followed a sigmoidal pattern (R2 = 0.91 for C. albicans, R2 = 0.86 for C. auris). The Cmax/MIC associated with stasis was 2.1 for C. albicans and 9 for C. auris. The probability of target attainment was >95% with 3 mg/kg for wild-type C. albicans isolates with MIC ≤2 mg/L and C. auris isolates with MIC ≤1 mg/L whereas 5 mg/kg L-AMB is needed for C. auris isolates with MIC 2 mg/L.
conclusionsL-AMB was 4-fold less active against C. auris than C. albicans. Candida auris isolates with CLSI MIC 2 mg/L would require a higher L-AMB dose.
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