Drug levels in septic patients treated with continuous renal replacement therapy receiving new beta-lactam dosage regimen

Objectives: A recent prospective study on beta-lactams levels in septic patients receiving continuous renal replacement therapy (CRRT) recommended the following dosage regimens: 2gq8h for ceftazidime or cefepime (CEF), 4gq6h for piperacillin-tazobactam (TZP), and 1gq8h for meropenem (MEM).1 We applied these regimens in our hospital since December 2009. The aim of our study was to evaluate the adequacy of this dosage strategy in a cohort of septic patients undergoing CRRT.Methods: Retrospective observational study from 01/01/2010 to 31/05/2011. Inclusion criteria were: a) sepsis, b) CRRT; c) treatment with CEF, TZP or MEM, and d) at least one measure of beta-lactam levels. Serum concentrations were measured by high-performance liquid chromatography (HPLC-UV). Blood samples were taken twice during the elimination phase after a 30-min intravenous administration of the drug. The two samples were used to calculate the time spent above the minimal inhibitory concentration (MIC), which was empirically considered as the clinical breakpoint for "difficult-to-treat" bacteria, such as Pseudomonas aeruginosa. Adequate therapy was defined as serum concentrations between 4 to 8 times the MIC during optimal periods of time for each drug: > 70% for CEF, > 50% for TZP, and > 40% for MEM. Underdosing and overdosing were defined as drug concentrations that were respectively < 4 times or > 8 times the MIC during optimal periods of time. Early and late phases of therapy were considered if drug levels measurement was performed within 48 hours or later on, respectively.Results: Fifty drugs levels were obtained from 36 patients; 15 during the early and 35 during the late septic phase. Drug levels obtained for each antibiotic are shown in Figure 1.Conclusions: Administering a higher beta-lactam dosage regimen for septic patients receiving CRRT avoided insufficient drug concentrations in most patients. Nevertheless, therapeutic drug monitoring should be performed routinely in order to adapt beta-lactam doses and to avoid drug accumulation .References: 1. Seyler L, Cotton F, Taccone FS, De Backer D, Macours P, Vincent JL, Jacobs F. Recommended beta-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Critical Care 2011, 15: R137.