| Autor: |
Sho Tashiro, Kazuaki Taguchi, Yuki Enoki, Kazuaki Matsumoto |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. |
| ISSN: |
1469-0691 |
| Popis: |
The pharmacokinetics/pharmacodynamics (PK/PD) characteristics of fidaxomicin (FDX) and vancomycin (VCM) against Clostridioides difficile infection (CDI) are yet to be elucidated because of the lack of an established PK/PD analysis method for intestinal infections and unabsorbed oral drugs. Here, we developed a feces-based PK/PD analysis method and determined the fecal PK/PD index with target values for FDX and VCM against CDI.Antimicrobial susceptibility, time-kill curves, and post-antibiotic effects (PAEs) of FDX and VCM against C. difficile were determined in vitro. Optimal fecal PK/PD indices with target values were determined from the results of PK and PD studies involving five-week-old female C57BL/6J mice infected with C. difficile ATCC® 43255. Minimum inhibitory concentration (MIC) breakpoints for C. difficile were estimated based on clinical data concerning fecal antibiotic concentrations in CDI patients.FDX and VCM inhibited C. difficile growth with time-dependent antibacterial activity and exerted PAEs. In CDI mouse model experiments, changes in C. difficile load and clinical cures (72 h-survival rates and clinical sickness score grading) were most highly correlated with the ratio of area under the fecal drug concentration-time curve to MIC (AUCThe developed in vivo feces-based PK/PD analysis method elucidated the optimal fecal PK/PD index with target values for FDX and VCM against CDI. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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