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

Infection & Chemotherapy 2020년 52권 3호 p.345 ~ 351
Santimaleeworagun Wichai, Hemapanpairoa Jatapat, Changpradub Dhitiwat, Thunyaharn Sudaluck,
소속 상세정보
 ( Santimaleeworagun Wichai ) - Silpakorn University Faculty of Pharmacy Department of Pharmacy
 ( Hemapanpairoa Jatapat ) - Burapha University Faculty of Pharmaceutical Sciences Department of Pharmacy Practice and Pharmaceutical Care
 ( Changpradub Dhitiwat ) - Phramongkutklao Hospital Department of Medicine
 ( Thunyaharn Sudaluck ) - Nakhonratchasima College Faculty of Medical Technology

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.

키워드

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

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