Weight‐based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups – a microdialysis porcine study

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2022-02, Vol.130 (2), p.111-118
• Main Authors: Tøstesen, Sara Kousgaard, Hanberg, Pelle, Bue, Mats, Thillemann, Theis Muncholm, Falstie‐Jensen, Thomas, Tøttrup, Mikkel, Knudsen, Martin Bruun, Schmedes, Anne Vibeke, Stilling, Maiken
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - analysis; Antibiotic Prophylaxis; Antibiotics; Body Weight; Catheters; Cefuroxime; Cefuroxime - administration & dosage; Disease prevention; Dosage; Drug Administration Schedule; Drug Dosage Calculations; Female; Health risks; Humans; Infections; Microdialysis; Minimum inhibitory concentration; Muscles; Orthopedic Procedures; orthopedic surgery; Orthopedics; Prophylaxis; Sampling; Skeletal muscle; Staphylococcal Infections - microbiology; Staphylococcal Infections - physiopathology; Staphylococcal Infections - prevention & control; Staphylococcus aureus - drug effects; Staphylococcus aureus - physiology; Subcutaneous Tissue - drug effects; surgical site infection; Surgical site infections; Surgical Wound Infection - microbiology; Surgical Wound Infection - physiopathology; Surgical Wound Infection - prevention & control; Swine; Tissues; weight‐based cefuroxime dosing
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/apm.13198

Antibiotic prophylaxis is a key element in prevention of surgical site infections. For the majority of orthopedic procedures, antibiotic administration follows fixed dosing regimens irrespective of weight. However, this may result in insufficient antibiotic target tissue concentrations and higher risk of surgical site infections in obese individuals. The aim of this study was to investigate the effect of weight‐based cefuroxime dosing on plasma and target tissue concentrations. Eighteen female pigs were allocated into three groups differentiated by weight: 53–57 kg, 73–77 kg, and 93–97 kg. Microdialysis catheters were placed for continuous sampling in bone, muscle, and subcutaneous tissue during an 8h sampling interval. Blood samples were collected as reference. Cefuroxime was administered intravenously as a bolus according to weight (20 mg/kg). The primary endpoint was the time above the cefuroxime minimal inhibitory concentration for Staphylococcus aureus (T > MIC (4 μg/mL)). Comparable target tissue T > MICs (4 μg/mL) were found between weight groups. Mean T > MIC ranged between 116–137 min for plasma, 118–154 min for bone, 109–146 min for the skeletal muscle, and 117–165 min for subcutaneous tissue across the groups. Weight‐based cefuroxime (20 mg/kg) dosing approach provides comparable perioperative plasma and target tissue T > MIC (4 μg/mL) in animals between 50–100 kg body weight, and thus a comparable prophylaxis of surgical site infections.