Evaluating eravacycline dosing regimens in the treatment of SSTIs caused by carbapenem-resistant Enterobacteriaceae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation

This study aimed to assess the efficacy of different eravacycline regimens for adult skin and soft-tissue infections (SSTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE). Monte Carlo simulations were performed using pharmacokinetic and pharmacodynamic data to calculate probabilities of target attainment (PTA) and cumulative fractions of response (CFR) according to 24-h free drug area under the concentration curve/minimum inhibitory concentration (MIC) targets. PTA results revealed that the standard 1 mg/kg intravenous q12h regimen exerted bacteriostatic/bactericidal efficacy against Enterobacteriaceae with MIC ≤ 0.5 μg/mL. All simulated regimens achieved CFR values exceeding 90% against Escherichia coli and carbapenem-resistant Escherichia coli. For Enterobacter cloacae complex and Klebsiella pneumoniae, doses of at least 1.5 and 2.5 mg/kg twice daily were required to meet therapeutic targets, respectively. However, few regimens yielded satisfactory efficacy against carbapenem-resistant Enterobacter cloacae complex and Klebsiella pneumoniae. These pharmacokinetic/pharmacodynamic simulations rationalized and optimized eravacycline dosing strategies for CRE-related SSTIs in adult patients.