Variations in pharmacokinetic-pharmacodynamic target values across MICs and their potential impact on determination of susceptibility test interpretive criteria
| Autor: | Seong H Jang, Kellie S. Reynolds, Abhay Joshi, Ursula Waack |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Microbiology (medical) Potential impact Veterinary medicine Pharmacokinetic pharmacodynamic Coefficient of variation Microbial Sensitivity Tests Biology Anti-Bacterial Agents Infectious Diseases Study report Area Under Curve Pharmacodynamics Mic values Animals Pharmacology (medical) Antibacterial drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:2884-2889 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkab282 |
| Popis: | Background An antibacterial drug’s susceptibility test interpretive criteria (STIC) are determined by integrating clinical, microbiological and pharmacokinetic-pharmacodynamic (PK-PD) data. PTA analysis plays a pivotal or supportive role in STIC determination and is heavily dependent on the PK-PD target values determined from animal PK-PD studies. Therefore, variations in PK-PD target values may impact STIC determination. Factors contributing to variation in the PK-PD target values include the number of and MICs for bacterial isolates used in animal PK-PD studies. Objectives To analyse the relationship between PK-PD target values and MICs, describe the variations in PK-PD target values of isolates and evaluate whether the proposed/target STICs were within the ranges of the MICs for isolates used in animal PK-PD studies. Methods A database was compiled for this research by screening animal PK-PD study reports submitted to the FDA from 10 new drug applications (NDAs). Results A relationship evaluation between PK-PD target values and MICs for tested isolates for seven drugs (that used AUC/MIC ratio as the PK-PD index) showed that, generally, the AUC/MIC values decreased with an increase in MIC. These target values were highly variable, with the percentage coefficient of variation ranging between 1% and 132% for isolates having the same MIC. For 16/27 (59%) drug/bacteria combinations from all 10 drugs, the proposed/target STICs were higher than the highest MIC for bacteria isolates evaluated, while 6/27 (22.5%) were lower. Conclusions This research suggests that careful considerations related to selection of bacterial isolates for animal PK-PD studies could strengthen the STIC determination process. |
| Databáze: | OpenAIRE |
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