Case-Control Study of Drug Monitoring of β-Lactams in Obese Critically Ill Patients
Open Access
- 1 February 2013
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 57 (2), 708-715
- https://doi.org/10.1128/aac.01083-12
Abstract
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 nonobese patients (body mass index of 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 β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-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 β-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 β-lactams should be continued in obese critically ill patients.Keywords
This publication has 27 references indexed in Scilit:
- Rapid quantification of six β-lactams to optimize dosage regimens in severely septic patientsTalanta, 2013
- Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactamsCritical Care, 2011
- Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapyCritical Care, 2011
- Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shockCritical Care, 2010
- Prospective monitoring of cefepime in intensive care unit adult patientsCritical Care, 2010
- Pharmacokinetic issues for antibiotics in the critically ill patientCritical Care Medicine, 2009
- Comparative Pharmacokinetics and Pharmacodynamic Target Attainment of Ertapenem in Normal-Weight, Obese, and Extremely Obese AdultsAntimicrobial Agents and Chemotherapy, 2006
- APACHE II-A Severity of Disease Classification SystemCritical Care Medicine, 1986
- APACHE IICritical Care Medicine, 1985
- Prediction of Creatinine Clearance from Serum CreatinineNephron, 1976