Beta-Lactams Clearance Is Related to the Intensity of Continuous Renal Replacement Therapy in Septic Patients

Abstract

Introduction: Severe sepsis may alter the pharmacokinetics (PKs) of B-lactams, and the use of continuous renal replacement therapy (CRRT) may further compromise them.Hypothesis: The aim of this study was to evaluate the correlation between B-lactams clearance and CRRT intensity.Methods: We reviewed the data of all patients undergoing CRRT and treated with ceftazidime/cefepime (CEF, 2gq8h), meropenem (MEM, 1gq8h) or piperacillin-tazobactam (TZP, 4gq6h) since January 2010. Serum drug concentrations were measured by high-performance liquid chromatography (HPLC-UV), twice during the elimination phase after a 30-min intravenous drug administration. Antibiotic PKs were calculated using a one-compartment model and the percentage of time spent above four times the MIC (%T>4xMIC) for Pseudomonas aeruginosa was obtained. CRRT data (blood flow, dialysate and ultrafiltrate rates) were collected and CRRT intensity was calculated as (dialysate + ultrafiltrate)/weight (kgs). Results are expressed as median [ranges].Results: A total of 73 serum levels were obtained in 50 patients (CEF = 10; MEM = 44; TZP = 19). There was considerable variability in B-lactam serum concentrations and pharmacokinetic variables. We found a weak, although significant, correlation of CRRT intensity with both B-lactams clearance (r=0.31, p = 0.007) and the %T>4xMIC (r= -0.27, p = 0.02). B-lactams clearance was increased in patients with higher CRRT intensity (45 ml/kg.h = 74.7 [51.3-131.7] ml/min; p = 0.02). Also, the %T > 4xMIC significantly decreased in patients with higher CRRT intensity (p=0.04).Conclusions: B-lactams concentrations and clearances during CRRT are quite variable. The intensity of CRRT may influence drug levels and elimination and should be taken into account when drug regimens are prescribed.info:eu-repo/semantics/publishedCommunication at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA)