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Single Dose Cefuroxime for Surgical Prophylaxis: Effects of Weight on Serum Concentrations and PK variables

par Hites, Maya ;Deprez, Guillaume ;Taccone, Fabio ;Wolff, Fleur ;Ickx, Brigitte ;Verleije, Anita ;Loi, Patrizia ;Closset, Jean ;Prevost, Jean-Marie ;Surin, Rudy;Cotton, Frédéric ;Jacobs, Frédérique
Référence IDWeek(2-6 October 2013: San Francisco, CA), IDWeek
Publication Publié, 2012-10

Abstract de conférence

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Résumé :

Background:Altered pharmacokinetics (PK) of b-lactams in obese patients may result in inadequate serum concentrations when standard dosage regimens are administered. The aim of our study was to evaluate the effects of weight on cefuroxime (CEF) concentrations and PKs during surgical prophylaxis. Methods:Prospective observational study from 10/2012 to 4/2013 at Erasme hospital, including all consecutive adult patients undergoing gastric bypass or partial hepatectomy and receiving CEF for surgical prophylaxis. Patients were a priori stratified into 2 weight groups : < 100 (Group A), or ³ 100 kgs (Group B). Serum samples were obtained at baseline, 30 minutes, 1 hour(H), 2H, and 3H after a 30-minutes administration of 1.5 g of CEF, and at end of surgery. Drug levels were measured by HPLC-UV. Free CEF fraction (fCEF) was calculated assuming protein binding of 50%. Creatinine clearance was evaluated with 24H urine collects (CLcr(24H)). Adequacy of serum concentrations was defined as fCEF > 8 mg/L (EUCAST clinical breakpoint for Enterobactericaea spp.), and was evaluated 3H after administration of CEF (fCEF180) and at end of surgery (fCEFend). Results were expressed as median (ranges) and counts (percentage) for each group, and compared using chi-square tests and the Wilcoxon Rank-Sum Test. A p < 0.05 was considered statistically significant. Results: 19 patients were included. Eight (88.9%) and 7 (78%) patients in Group A had adequate fCEF180 and fCEFend, compared to 4 (40%) and 5 (50%) patients in group B (p=0.03 and NS, respectively). Conclusion:This is the first PK study of CEF in obese patients. As weight increased, CL and VD of CEF and CLcr(24H) increased, while fCEF180 decreased. Higher dosage regimens of CEF in patients weighing more than100 kg may be warranted to obtain effective prophylaxis : a second dose of CEF may be necessary if surgery lasts more than 180 minutes.