Broad-spectrum β-lactams in obese non-critically ill patients

OBJECTIVES: Obesity may alter the pharmacokinetics of beta-lactams. The goal of this study was to evaluate if and why serum concentrations are inadequate when standard beta-lactam regimens are administered to obese, non-critically ill patients. SUBJECTS AND METHODS: During first year, we consecutively included infected, obese patients (body mass index (BMI) >= 30 kg m(-2)) who received meropenem (MEM), piperacillin-tazobactam (TZP) or cefepime/ceftazidime (CEF). Patients with severe sepsis or septic shock, or those hospitalized in the intensive care unit were excluded. Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography. We evaluated whether free or total drug concentrations were >1 time (fT > minimal inhibition concentration (MIC)) or >4 times (T>4MIC) the clinical breakpoints for Pseudomonas aeruginosa during optimal periods of time: >= 40% for MEM, >= 50% for TZP and >= 70% for CEF. RESULTS: We included 56 patients (median BMI: 36 kg m(-2)): 14 received MEM, 31 TZP and 11 CEF. The percentage of patients who attained target fT >MIC and T>4MIC were 93% and 21% for MEM, 68% and 19% for TZP, and 73% and 18% for CEF, respectively. High creatinine clearance (107 (range: 6-398) ml min(-1)) was the only risk factor in univariate and multivariate analyses to predict insufficient serum concentrations. CONCLUSIONS: In obese, non-critically ill patients, standard drug regimens of TZP and CEF resulted in insufficient drug concentrations to treat infections due to less susceptible bacteria. Augmented renal clearance was responsible for these low serum concentrations. New dosage regimens need to be explored in this patient population (EUDRA-CT: 2011-004239-29).