Matthieu Boisson1,2,3, Bruna Gaelzer Silva Torres1,2, Sabrina Yani3, William Couet1,2,4, Olivier Mimoz1,2,5, Claire Dahyot-Fizelier1,2,3, Sandrine Marchand1,2,4, Nicolas Grégoire1,2,4. 1. Inserm U1070, Pôle Biologie Santé, 1 rue Georges Bonnet, Poitiers, France. 2. Université de Poitiers, UFR Médecine-Pharmacie, 6 rue de la milétrie, Poitiers, France. 3. Département d'Anesthésie-Réanimation, CHU de Poitiers, 2 rue de la milétrie, Poitiers, France. 4. Service de Toxicologie-Pharmacocinétique, CHU de Poitiers, 2 rue de la milétrie, Poitiers, France. 5. Service des Urgences & SAMU 86 - Centre 15, CHU de Poitiers, 2 rue de la milétrie, Poitiers, France.
Abstract
OBJECTIVES: Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. METHODS: Data from eight patients undergoing major abdominal surgery were analysed using population pharmacokinetic modelling, and Monte Carlo simulations were conducted to determine the PTA for aerobic and anaerobic pathogens. ClinicalTrials.gov: NCT02703857. RESULTS: Only 2.3% and 47.4% of the simulated patients maintained cefoxitin subcutaneous concentrations above the MIC breakpoint for anaerobic (MIC = 16 mg/L) and aerobic (MIC = 8 mg/L) pathogens, respectively. New simulations with administration of a loading dose followed by a constant infusion of cefoxitin were conducted and demonstrate that, notwithstanding using the same total dose per unit of time, continuous infusion of cefoxitin can cover aerobes in 96.6% of the simulated patients, but remains insufficient for anaerobic bacteria. CONCLUSIONS: The recommended dosing regimen of cefoxitin is insufficient for covering the usual bacteria during abdominal surgery. Administration of a loading dose followed by a constant infusion should be considered for aerobic bacteria and cefoxitin should be avoided as SAP for anaerobic bacteria.
OBJECTIVES:Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. METHODS: Data from eight patients undergoing major abdominal surgery were analysed using population pharmacokinetic modelling, and Monte Carlo simulations were conducted to determine the PTA for aerobic and anaerobic pathogens. ClinicalTrials.gov: NCT02703857. RESULTS: Only 2.3% and 47.4% of the simulated patients maintained cefoxitin subcutaneous concentrations above the MIC breakpoint for anaerobic (MIC = 16 mg/L) and aerobic (MIC = 8 mg/L) pathogens, respectively. New simulations with administration of a loading dose followed by a constant infusion of cefoxitin were conducted and demonstrate that, notwithstanding using the same total dose per unit of time, continuous infusion of cefoxitin can cover aerobes in 96.6% of the simulated patients, but remains insufficient for anaerobic bacteria. CONCLUSIONS: The recommended dosing regimen of cefoxitin is insufficient for covering the usual bacteria during abdominal surgery. Administration of a loading dose followed by a constant infusion should be considered for aerobic bacteria and cefoxitin should be avoided as SAP for anaerobic bacteria.
Authors: Costanza Vicentini; Maria Michela Gianino; Alessio Corradi; Noemi Marengo; Valerio Bordino; Silvia Corcione; Francesco Giuseppe De Rosa; Giovanni Fattore; Carla Maria Zotti Journal: Antibiotics (Basel) Date: 2021-03-04