ArticleAntimicrobial agents and chemotherapy2011
Use of pharmacokinetic-pharmacodynamic analyses to optimize therapy with the systemic antifungal micafungin for invasive candidiasis or candidemia.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Choosing the Right Antifungal Agent in ICU Patients.Advances in therapy · 2019Pooled it
- Antifungal pharmacodynamics: Latin America's perspective.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesPooled it
- Outcomes byAntimicrobial agents and chemotherapy · 2024Trial
- Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.Antimicrobial agents and chemotherapy · 2017Trial
- Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection.Antimicrobial agents and chemotherapy · 2016Trial
- Fractal geometry and the pharmacometrics of micafungin in overweight, obese, and extremely obese people.Antimicrobial agents and chemotherapy · 2011Trial
- Effect of polymerase chain reaction-based antifungal stewardship on candidemia management in small- and medium-sized hospitals.Journal of pharmaceutical health care and sciences · 2026Article
- Evaluation of anAntimicrobial agents and chemotherapy · 2026Article
- From AUC/MIC to AUCss and Cmin: Optimizing Micafungin Therapy in the Critically Ill through Model-Informed Precision Dosing.The AAPS journal · 2025Article
- Optimizing Micafungin Dosing in Patients with Critically Ill Candidemia and Trends ofDrug design, development and therapy · 2025Article
- Impact of Micafungin on Candida auris β-glucan Masking and Neutrophil Interactions.The Journal of infectious diseases · 2024Article
- Evaluation of Population Pharmacokinetic Models of Micafungin: Implications for Dosing Regimen Optimization in Critically Ill Patients.Pharmaceutics · 2024Review
- A new PK/PD target for assessing efficacy of micafungin against Candida parapsilosis.The Journal of antimicrobial chemotherapy · 2024Article
- Population pharmacokinetic modeling and target attainment analyses of rezafungin for the treatment of candidemia and invasive candidiasis.Antimicrobial agents and chemotherapy · 2023Article
- Critical appraisal beyond clinical guidelines for intraabdominal candidiasis.Critical care (London, England) · 2023Review
- 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
- Population Pharmacokinetic Model and Optimal Sampling Strategies for Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.Antimicrobial agents and chemotherapy · 2022Article
- Postantifungal Effect of Antifungal Drugs againstJournal of fungi (Basel, Switzerland) · 2022Review
- Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.Antimicrobial agents and chemotherapy · 2022Article
- Caspofungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-Abdominal Infections: A Prospective Cohort Study.Clinical pharmacokinetics · 2022Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Echinocandins have become a first-line therapy for invasive candidiasis (IC). Using phase 3 trial data for patients with IC, pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy for micafungin were examined. Micafungin exposures were estimated using a population pharmacokinetic model, and univariable and multivariable logistic regressions were used to identify factors associated with outcome, including the micafungin area under the concentration-time curve (AUC)/MIC ratio. Monte Carlo simulation was used to evaluate the probability of achieving AUC/MIC ratios associated with efficacy. Mycological and clinical success rates for evaluable cases were 89.4 and 90.9, respectively. MIC50s and MIC90s for Candida species inhibition were 0.008 and 0.5 mg/liter, respectively. The median AUC/MIC ratio was 15,511 (range, 41.28 to 98,716). Univariable analyses revealed a significant relationship between the AUC/MIC ratio and mycological response, with the worst response being among patients with lower (≤3,000) AUC/MIC ratios (P=0.005). For patients with Candida parapsilosis, AUC/MIC ratios of ≥285 were predictive of a higher mycological response (P=0.11). Multivariable logistic regression demonstrated the AUC/MIC ratio, APACHE II score, and history of corticosteroid use to be significant independent predictors of a favorable response. PK-PD target attainment analyses suggested that 76.7% and 100% of patients would achieve an AUC/MIC ratio of ≥3,000 for an MIC of 0.03 mg/liter and an AUC/MIC ratio of ≥285 for an MIC of <0.5 mg/liter, respectively. The identification of a lower AUC/MIC ratio target for C. parapsilosis than other Candida species suggests consideration of species-specific echinocandin susceptibility breakpoints and values that are lower than those currently approved by regulatory agencies.
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