First-time cefuroxime target tissue concentrations in long-lasting spine surgery: Continuous evaluation after repeated weight-dosed administrations

Abstract

Aims: Antimicrobial prophylaxis is central in preventing postoperative spine infections, yet knowledge on clinical target spine tissue concentrations remain limited. Current dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures, non-clinical evidence and methodology of variying quality. The objective was to continuously evaluate peri- and postoperative cefuroxime target tissue concentrations in long-lasting spine surgery.

Methods: Twenty patients scheduled for spine deformity surgery with hypotensive anaesthesia completed the study. Weight-dosed cefuroxime was administered intravenously (20 mg/kg) to all patients preoperativey and after 4 h. Microdialysis probes were placed in vertebral bone (intraoperative sampling), paravertebral muscle, subcutaneous tissue and profoundly/superficially in the wound. Microdialysates and plasma samples were obtained for up to 12 h. The primary endpoint was the time with cefuroxime concentrations above the minimal inhibitory concentration for Staphylococcus aureus of 4 μg/mL as a percentage (%fT>MIC4).

Results: The median cefuroxime %fT>MIC4 (range) of patients' individual surgery time was 100% (100-100) in all investigated tissues and plasma. Median cefuroxime %fT>MIC4 (range) in the first dosing interval was 93% (93-93) in vertebral bone, paravertebral muscle and subcutaneous tissue, and 100% (99-100) in plasma. Median cefuroxime %fT>MIC4 (range) in the second dosing interval was 85% (52-100) in paravertebral muscle, 94% (52-100) in subcutaneous tissue, 99% (71-100) in the profound wound, 100% (72-100) in the superficial wound, and 70% (42-100) in plasma.

Conclusions: Repeated weight-dosed intravenous cefuroxime administrations (20 mg/kg) provided homogenous and sufficient intraoperative target tissue exposure of cefuroxime (100% fT>MIC4) in long-lasting spine surgery with hypotensive anaesthesia and postoperative exposure (>4 μg/mL) for 5.5-7.5 h.

Keywords: antibiotic prophylaxis; microdialysis; pharmacodynamics; pharmacokinetics; spine surgery; weight‐dosage.