title: Evaluation of total body weight and body mass index cut-offs for increased cefazolin dose for surgical prophylaxis.
abstract: French and American guidelines recommend increased dosage regimens of cefazolin (CFZ) for surgical prophylaxis in patients with a body mass index (BMI) ≥ 35 kg/m2or with a total body weight (TBW) ≥ 120 kg. The objective of this study was to evaluate the accuracy of these cut-offs in identifying patients who require CFZ dose adjustment. A pharmacokinetic study was conducted in patients of varying TBW and BMI who received 2 g of CFZ intravenously for prophylaxis prior to digestive surgery. Adequacy of therapy, defined as a serum concentration of unbound CFZ (fCFZ) ≥ 4 mg/L, was evaluated 180 min (T180) and 240 min (T240) after the start of CFZ infusion. Possible factors associated with insufficient fCFZ levels were also assessed. A P-value of <0.05 was considered statistically significant. A total of 63 patients were included in the study, categorised according to BMI (<35 kg/m2, 20 patients; and ≥35 kg/m2, 43 patients) and TBW (<120 kg, 41 patients; and ≥120 kg, 22 patients). All patients had adequate drug levels at T180but only 40/63 patients (63%) had adequate levels at T240. At T240, therapy was adequate in 15/20 patients (75%) and 25/43 patients (58%) with BMI <35 kg/m2and ≥35 kg/m2, respectively (P = 0.20), and in 28/41 patients (68%) and 12/22 patients (55%) with TBW <120 kg and ≥120 kg, respectively (P = 0.28). No factor associated with insufficient fCFZ was identified. In conclusion, current BMI and TBW cut-offs are poor indicators of which patients could benefit from increased CFZ dosage regimens.
authors.affiliation: Department of Infectious Diseases, CUB-Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium. Electronic address: Maya.Hites@erasme.ulb.ac.be.
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.affiliation: Department of Clinical Chemistry, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deprez
authors.affiliation: Department of Clinical Chemistry, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fleur
authors.initials: F
authors.lastname: Wolff
authors.affiliation: Department of Anesthesiology, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Ickx
authors.affiliation: Department of Anesthesiology, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Anita
authors.initials: A
authors.lastname: Verleije
authors.affiliation: Department of Digestive Surgery, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Closset
authors.affiliation: Department of Digestive Surgery, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Loi
authors.affiliation: Department of Infectious Diseases, CUB-Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Prévost
authors.affiliation: Department of Intensive Care, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Taccone
authors.affiliation: Research Center of Epidemiology, Biostatistics and Clinical Research, School of Public Health, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Judith
authors.initials: J
authors.lastname: Racapé
authors.affiliation: Department of Clinical Chemistry, CUB-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cotton
authors.affiliation: Department of Infectious Diseases, CUB-Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D015992:Body Mass Index; D001835:Body Weight; D002437:Cefazolin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin
keywords: Non-obese patients; Obesity; Pharmacodynamics; Pharmacokinetics; β-Lactam antibiotics