In Vitro Activity, Pharmacodynamic Profile and Dose Optimization of Biapenem against NDM and OXA-48-like Carbapenemase Producing Klebsiella pneumoniae: a Multicenter Study in Thailand

Abstract

BackgroundBiapenem (BIPM) exhibited a less efficient substrate for various Metallo-β-lactamase (MBL) than other carbapenems. ObjectiveWe aimed to evaluate in vitro susceptibility data of BIPM, and optimal dose based on Monte Carlo simulation to extend treatment options. MethodsWe collected 192 carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates from unique patients among multicenters in Thailand, from June 2019–March 2023. BIPM disk diffusion and broth-microdilution testing were performed to obtain minimum inhibitory concentration (MIC). Each BIPM regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). ResultsThe most common genotypes among 192 CRKP isolates were blaOXA-48 (62.3%) blaOXA-48+blaNDM (22.6%) and blaNDM (15.1%). BIPM showed 22.4 and 28.6% susceptible rate when interpreted at clinical breakpoints of 1 and 2 mg/L. The MIC50 and MIC90 of BIPM against CRKP were 16 and 32 mg/L. The BIPM dosing regimens of 300 mg q 6 h infused 6 h and 600 mg q 8 h infused 8 h met the PTA target of %fTime >MIC at 50, 75 and 100% against isolates MICs of ≤2 mg/L. Based on CFR ≥90%, no BIPM regimens were effective against all the studied CRKP isolates. ConclusionBIPM exhibited a partially susceptible rate among the CRKP isolates in Thailand. The current suggested dose of BIPM with prolonged infusion appears appropriate regimen against CRKP MICs of ≤2 mg/L. However, the empirical use of BIPM for severe CRE infection is not recommended unless the susceptibility has been confirmed.