Pharmacokinetics of biapenem in critically ill patients

Abstract

Objective. To assess biapenem PK parameters in critically ill adult patients and define the optimal dosing regimens based on TDM data. Materials and Methods. An open, prospective, uncontrolled, single-center study based on City Clinical Hospital No. 24, Moscow (October 2022 – April 2023), included patients over 18 years of age with a diagnosed severe bacterial infection received 600 mg of biapenem as 3-hour intravenous infusion every 12 hours in the intensive care unit. Blood sampling during the TDM included taking blood samples immediately before the next infusion of biapenem to determine the residual concentration (Ctrough) and immediately after the end of the infusion to determine the peak concentration (Cmax). Concentrations were assessed using HPLC-UV method. Results. Total population – 20 patients (75% ≥ 60 years; 65% women). The main indications for biapenem were lower respiratory tract infections (80%) and intra-abdominal infections (35%). Bacterial culture tests revealed growth in 45% (Klebsiella pneumoniae – 87,5%). During the TDM 40 samples were obtained (Cmax from 15 to 42 mg/l (mean – 28.7 mg/l), Ctrough from 0.5 to 15 mg/l (mean – 3.56 mg/l)). The Kel value ranged from 0.09 to 0.48 1/h (mean – 0.29 1/h); Vd – from 7.41 to 42.49 l (mean – 16.33 l); T1/2 – from 1.4 to 7.5 hours (mean 2.94 hours). Probability of target attainment (%fT ≥ MIC) was assessed depending on MIC. For MIC of 2 mg/l, 40%fT ≥ MIC was achieved in 100%, 60%fT ≥ MIC – in 100%; 80%fT ≥ MIC – in 75%. For MIC – 8 mg/l, 40%fT ≥ MIC was achieved in 90%, 60%fT ≥ MIC – in 45%, 80%fT ≥ MIC – in 15%. Conclusions. The dosing regimen 600 mg of biapenem as 3-hour intravenous infusion every 12 hours demonstrated achievement of effective antibiotic concentrations in blood plasma of critically ill patients exceeding the MIC (2 mg/l). To manage patients infected with resistant strains (MIC of 4–16 mg/l) it is necessary to perform additional studies assessing PK parameters of biapenem at higher doses.