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Standard Dosage Regimens of Broad-Spectrum Beta-lactams are Inadequate to Treat "Difficult-to-Treat" Pathogens in Obese Non-critically Ill Patients

par Hites, Maya ;Wolff, Fleur ;Taccone, Fabio ;Maillart, Evelyne ;Deprez, Guillaume ;Araci, J;Surin, Rudy;Cotton, Frédéric ;Jacobs, Frédérique
Référence Interscience Conference on Antimicrobial Agents and Chemotherapy(LII: 9-12 September 2012: San Francisco), 52nd ICAAC
Publication Publié, 2012-09

Abstract de conférence

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Résumé :

Background: Altered pharmacokinetics (PK) in obese, non-critically ill patients may result in inadequate serum ß-lactam concentrations when standard dosage regimens (SDRs) are administered. The aim of our study was to monitor and evaluate broad-spectrum ß-lactam (BSBL) concentrations in these patients when SDRs were administered. If drug levels were insufficient, dosage regimens were increased (IDRs), and drug levels were re-monitored. Methods: Prospective interventional study from October 2011 to May 2012 at Erasme hospital. We included all consecutive obese (body mass index = 30 kg/m2) adult patients (pts) treated with a BSBL [cefepime or ceftazidime (CEF), piperacillin-tazobactam (TZP), or meropenem (MEM)]. Serum samples were taken during the elimination phase after a 30 minute IV infusion to estimate PK and calculate the time spent above the MIC. Serum levels were measured by HPLC. Adequate therapy: serum levels between 4-8 times the MIC for « difficult-to-treat (DTT)» pathogens, such as Pseudomonas aeruginosa during optimal periods of time: > 70% for CEF, > 50% for TZP, >40% for MEM. Results: 38 drug levels were obtained in 29 pts treated with SDRs. Median BMI was 35 kg/m2, and creatinine clearance 91.5 ml/min. 29/38 (3/5 CEF, 10/11 MEM, 16/22 TZP) drug levels were insufficient to treat “DTT” pathogens. 4/10 drug levels in 5 pts treated with IDRs (1g q6h of MEM in 3-hour infusion and a median of 22 g/day of TZP in continuous infusion) were adequate (1/2 MEM, 3/8 TZP). Conclusions: This is the largest prospective case series of measured BSBL serum levels in infected, obese, non-critically ill pts. SDRs resulted in insufficient serum concentrations to treat « DTT» pathogens in most of these pts. Recommended dosage regimens of BSBL for obese, non-critically ill pts need to be reconsidered.