Competence Mining of Vancomycin (VAN) in the Management of Infections Due to Bacterial Strains With High VAN Minimum Inhibitory Concentrations (MICs): A Novel Dosing Strategy Based on Pharmacokinetic/Pharmacodynamic Modeling

作者：Xiangqing Song, Meizi Zeng, Yi Wu, Yong Pan · 发表于：Frontiers in Microbiology · 年份：2021 · DOI：10.3389/fmicb.2021.649757 · 被引用次数：8 · 研究领域：Antimicrobial Resistance in Staphylococcus、Antibiotics Pharmacokinetics and Efficacy、Antibiotic Resistance in Bacteria

The increasing emergence of bacterial strains with high VAN MICs (BS H – V AN– M ), such as Enterococcus faecalis , Enterococcus faecium , Staphylococcus aureus , Staphylococcus epidermidis , and Streptococcus bovis , results in growing concern that VAN is not effective against these isolates. Due to the limited data on VAN against BS H–VAN–M and the application limits of drugs currently considered to be effective for BS H–VAN–M , exploration of “new usages for old drugs” is reasonable to improve and maximize the efficacy of existing antibiotics. This study aimed to construct a novel dosing strategy to mine the competence of VAN in the management of BS H–VAN–M infections. Herein, we optimized the traditional intermittent i.v. infusion (TIII) method to create an optimal two-step infusion (OTSI). With pharmacokinetic (PK)/pharmacodynamic (PD) modeling at the targeted ratio of the daily area under the concentration-time curve (AUC 0 – 24 ) to the minimum inhibitory concentration (MIC) (AUC 0 – 24 /MIC) of 400, we used Monte Carlo simulations to evaluate the efficacy of 25 VAN regimens (including 15 OTSI regimens and 10 TIII regimens with daily doses of up to 6 g) to treat pneumonia, meningitis, sternal osteomyelitis, mastitis, pleuritis, bacteremia, and bacterial pericarditis resulting from isolates with MICs of ≤64 mg/L and to the current E. faecalis , E. faecium , S. aureus , S. epidermidis , and S. bovis populations with a pooled MIC distribution. Our data indicated that 4 g/...