Pharmacokinetics of Meropenem in Burn Patients with Infections Caused by Gram Negative Bacteria: Are We Getting Close to the Right Treatment?

Abstract Background Infections caused by multi drug resistant (MDR) gram negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapies in burn patients in which the pathophysiological changes strongly influence the pharmacokinetic (PK) parameters. Objective Aim of the study was to describe the PK parameters of meropenem in a population of burn patients. Methods Blood samples were collected immediately before (T0), and after 2 and 5 hours after intravenous drug administration. Plasma meropenem concentrations were determined using an ultra performance liquid chromatography-photodiode array method. Result Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for P. Aeruginosa and A. Baumannii isolated from blood or wounds. The mean Cmax, Cmin, AUC0-24, half-life (T1/2), clearance (CL) and volume distribution (Vd) were: 28.9 mg/L, 3.7 mg/L, 109.2 mg/Lh, 2.4 h, 17.1 L/h, 47.6 L respectively. Six patients (35%) achieved a Cmin ≥ 3.3 mg/L and seven patients (41%) achieved a Cmax ≥ 28,4 mg/L, while 9 patients (53%) achieved an AUC0-24 of 226 mg/Lh. Given a MIC of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises up to 2 mg/L (ECOFF), only 5 patients reached the desired AUC/MIC. Regarding ft > MIC of 2 mg/L with infusion time of 2 h, 13 patients (76%) achieved the PK target (>75%). Conclusion These data suggest that a combined 2 h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.