Drug monitoring of ?-lactams in obese critically ill patients: a case-control study.
Antimicrob Agents Chemother. 2012 Nov 12;
Authors: Hites M, Taccone FS, Wolff F, Cotton F, Beumier M, De Backer D, Roisin S, Lorent S, Surin R, Seyler L, Vincent JL, Jacobs F
Abstract
Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum ?-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients, (body mass index ?30 kg/m(2)), treated with a broad-spectrum ?-lactam in whom therapeutic drug monitoring was performed and compared them to those obtained in critically non-obese patients (body mass index < 25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. 68 serum levels were obtained from 49 obese patients. There was considerable variability in ?-lactam serum concentrations (coefficient of variation of 50% to 92% for the 3 drugs). Standard drug regimens of ?-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for over-dosage and a protective factor for insufficient ?-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and SOFA score to 68 serum levels measured in 59 non-obese patients. The only difference observed between the 2 cohorts was in the sub-group of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of ?-lactams should be continued in obese critically ill patients.
PMID: 23147743 [PubMed - as supplied by publisher]