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

By Marjorie Beumier, Maya Hites, Fleur Wolff, Frédéric Cotton, Frédérique Jacobs, Jean Louis Vincent and Fabio Taccone


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 (<25 ml/kg.h = 54.0 [31.5-88.2] ml/min; 25-30 ml/kg.h= 48.6 [31.8-106.0] ml/min; 31-45 ml/kg.h = 117.0 [60.7-145.9] ml/min; >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 at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA)

Topics: Dermatologie
Year: 2012
DOI identifier: 10.1097/01.ccm.0000425125.36285.33
OAI identifier:
Provided by: DI-fusion
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