ArticleAntimicrobial agents and chemotherapy2015
Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection model.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi.Antimicrobial agents and chemotherapy · 2017Trial
- Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi.Antimicrobial agents and chemotherapy · 2016Trial
- Pharmacodynamics of isavuconazole in experimental invasive pulmonary aspergillosis: implications for clinical breakpoints.The Journal of antimicrobial chemotherapy · 2016Trial
- Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort.JAC-antimicrobial resistance · 2026Article
- Prospective study of pharmacokinetics of isavuconazole in critically ill patients undergoing continuous hemodialysis with and without acute-on-chronic liver failure.Annals of intensive care · 2026Article
- Exploratory model-based optimizing isavuconazole dosing regimens forFrontiers in cellular and infection microbiology · 2026Article
- Isavuconazole in Pediatric Invasive Fungal Infections: Outcomes and Therapeutic Drug Monitoring in a Chinese Multicenter Case Series.Infection and drug resistance · 2026Article
- Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study.The Journal of antimicrobial chemotherapy · 2024Observational
- Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions.The Journal of antimicrobial chemotherapy · 2024Article
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.Clinical pharmacokinetics · 2024Review
- High Variability in Isavuconazole Unbound Fraction in Clinical Practice: A Call to Reconsider Pharmacokinetic/Pharmacodynamic Targets and Breakpoints.Clinical pharmacokinetics · 2023Article
- Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2023Article
- A Hybrid Algorithm Combining Population Pharmacokinetic and Machine Learning for Isavuconazole Exposure Prediction.Pharmaceutical research · 2023Article
- Article
- Resistance profiling ofEmerging microbes & infections · 2022Article
- Antifungal Resistance and the Role of New Therapeutic Agents.Current infectious disease reports · 2022Review
- Population Pharmacokinetics and Pharmacodynamic Target Attainment of Isavuconazole againstPharmaceutics · 2021Article
- Review
- Efficacy and Associated Drug Exposures of Isavuconazole and Fluconazole in an Experimental Model of Coccidioidomycosis.Antimicrobial agents and chemotherapy · 2021Article
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Azole resistance is an emerging problem in Aspergillus fumigatus which translates into treatment failure. Alternative treatments with new azoles may improve therapeutic outcome in invasive aspergillosis (IA) even for strains with decreased susceptibility to current azoles. The in vivo efficacy of 0.25, 1, 4, 16, 64, 128, 256, and 512 mg/kg of body weight/day prodrug isavuconazonium sulfate (BAL8557) (isavuconazole [ISA]-equivalent doses of 0.12, 0.48, 1.92, 7.68, 30.7, 61.4, 122.9, and 245.8 mg/kg/day, respectively) administered by oral gavage was assessed in an immunocompetent murine model of IA against four clinical A. fumigatus isolates: a wild-type isolate (ISA MICEUCAST, 0.5 mg/liter) and three azole-resistant isolates harboring substitutions in the cyp51A gene: G54W (ISA MIC(EUCAST), 0.5 mg/liter), M220I (ISA MIC(EUCAST), 4 mg/liter), and TR34/L98H (ISA MIC(EUCAST), 8 mg/liter). The maximum effect (100% survival) was reached at a prodrug isavuconazonium sulfate dose of 64 mg/kg for the wild-type isolate, 128 mg/kg for the G54W mutant, and 256 mg/kg two times per day (q12) for the M220I mutant. A maximum response was not achieved with the TR34/L98H isolates with the highest dose of prodrug isavuconazonium sulfate (256 mg/kg q12). For a survival rate of 50%, the effective AUC(0-24)/MIC(EUCAST) ratio for ISA total drug was 24.73 (95% confidence interval, 22.50 to 27.18). The efficacy of isavuconazole depended on both the drug exposure and the isavuconazole MIC of the isolates. The quantitative relationship between exposure and effect (AUC(0-24)/MIC) can be used to optimize the treatment of human infections by A. fumigatus, including strains with decreased susceptibility.
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