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Case-control study of drug monitoring of ?-lactams in obese critically ill patients.

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 of ? 30 kg/m(2)) treated with a broad-spectrum ?-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight 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 three 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 overdosage 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 sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup 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.

SUBMITTER: Hites M

PROVIDER: S-EPMC3553684 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Case-control study of drug monitoring of β-lactams in obese critically ill patients.

Hites Maya M Taccone Fabio Silvio FS Wolff Fleur F Cotton Frédéric F Beumier Marjorie M De Backer Daniel D Roisin Sandrine S Lorent Sophie S Surin Rudy R Seyler Lucie L Vincent Jean-Louis JL Jacobs Frédérique F

Antimicrobial agents and chemotherapy 20121112 2

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-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 of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically n ...[more]

PMID: 23147743

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Project description:Patients admitted to the intensive care unit often develop hyperglycaemia, but the underlying mechanisms have not been fully described. The incretin effect is reduced in patients with type 2 diabetes. Type 2 diabetes and critical illness have phenotypical similarities, such as hyperglycaemia, insulin resistance and systemic inflammation. Previous studies have shown beneficial effects of exogenous glucagon-like peptide (GLP)-1 on glycaemia in critically ill patients, a phenomenon also seen in patients with type 2 diabetes. In this study, we hypothesised that the incretin effect, which is mediated by the incretin hormones GLP-1 and glucose-dependent insulinotropic peptide (GIP), is impaired in critically ill patients.The incretin effect (i.e., the relative difference between the insulin response to oral and intravenous glucose administration) was investigated in a cross-sectional case-control study. Eight critically ill patients without diabetes admitted to a mixed intensive care unit and eight healthy control subjects without diabetes, matched at group level by age, sex and body mass index, were included in the study. All subjects underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the next day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide and plasma levels of GLP-1, GIP, glucagon and proinflammatory cytokines were measured intermittently. The incretin effect was calculated as the increase in insulin secretion during oral versus intravenous glucose administration in six patients. The groups were compared using either Student's t test or a mixed model of repeated measurements.Blood glucose levels were matched between the OGTT and the IVGI in both groups. Compared with control subjects, proinflammatory cytokines, tumour necrosis factor ? and interleukin 6, were higher in patients than in control subjects. The endogenous response of GIP and glucagon, but not GLP-1, to the OGTT was greater in patients. The insulin response to the OGTT did not differ between groups, whereas the insulin response to the IVGI was higher in patients. Consequently, the calculated incretin effect was lower in patients (23 vs. 57%, p=0.003).In critically ill patients, the incretin effect was reduced. This resembles previous findings in patients with type 2 diabetes.ClinicalTrials.gov identifier: NCT01347801 . Registered on 2 May 2011.

Dataset Information

Case-control study of drug monitoring of ?-lactams in obese critically ill patients.

Publications

Case-control study of drug monitoring of β-lactams in obese critically ill patients.

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