Towards Optimization of Ceftazidime Dosing in Intensive Care Unit Obese Patients: the end of the “one-size-fits-all” approach?

Abstract

Abstract BACKGROUND Ceftazidime (CAZ) is commonly used as pivotal antibiotic against pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate impact of obesity and renal function on CAZ plasma concentrations and dosing regimen in ICU patients. METHODS All consecutive adult patients from 6 ICUs, treated with continuous CAZ infusion and under Therapeutic Drug Monitoring evaluation were included. Obesity was defined as body mass index ≥ 30 kg/m². Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration formula. CAZ recommended levels for plasma concentrations were between 35 and 80 mg/L. RESULTS A total of 111 patients (45 obese), weighted 90 (±24,4) kg, were included. Mean GFR was 82 mL/min/1,73m2 (±40,3). Recommended CAZ plasma concentrations were achieved only for 49,6% patients, with median dosing regimen of 6g/d. Obese patients had lower CAZ plasma concentrations compared to non-obese patients (37.8 vs 56.3 mg/L; p=0.0042*) despite similar dosing regimens (5.83g/d vs 5.52 g/d, p= 0.2529). Almost all Augmented Renal Clearance patients were underdosed despite CAZ dosing of 6,6g/d (±0,8). Considering weight-based CAZ dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS ICU obese patients required significantly greater CAZ amount to achieve target range. Tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.