Optimizing the Dosing Regimens of Tigecycline against Vancomycin-Resistant Enterococci in the Treatment of Intra-abdominal and Skin and Soft Tissue Infections

Abstract

Tigecycline was previously considered to have activity against vancomycin-resistant Enterococcus (VRE) isolates, but the optimal dose was not clarified. Thus, this study assessed the in vitro activity of tigecycline against clinical VRE isolates to determine its optimal regimens for complicated intra-abdominal (cIAIs) and complicated skin/soft tissue infections (cSSTIs). We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response for the ratio of the free area under the curve to the minimum inhibitory concentration (MIC) (fAUIC₂₄), which were 17.9 and 6.9 for treating cSSTIs and cIAIs, respectively. All clinical isolates were Enterococcus faecium. Only a maintenance dose of 200 mg/day tigecycline gave the target attainment of fAUIC₂₄ >17.9, and PTA exceeded 90% for MIC ≤0.38 μg/mL. Meanwhile, this dose gave the target attainment of fAUIC₂₄ >6.9, and PTA exceeded 90% for MIC ≤1 μg/mL. All simulated tigecycline dosing regimens met the fAUIC₂₄ targets more than 90% of the cumulative fraction of response. Despite its apparent efficacy, a daily tigecycline dose of 200 mg is recommended for VRE isolates with MICs of ≤0.38 μg/mL and ≤1 μg/mL for treating cSSTIs and cIAIs, respectively.

Keywords: Dosing regimen; Minimum inhibitory concentration; Monte Carlo simulation; Tigecycline; Vancomycin-resistant Enterococcus.