Pharmacokinetics of cefazolin in bariatric surgery patients: a preoperative perspective

Optimal cefazolin dosing for surgical prophylaxis in patients with severe obesity remains controversial, particularly regarding tissue exposure at the surgical site. Plasma concentrations may not reliably reflect pharmacologically active antibiotic levels in target tissues. This study aims to characterize total and calculated unbound concentrations of cefazolin in subcutaneous adipose tissue, dermis and plasma in patients with severe obesity undergoing bariatric surgery, and to assess pharmacodynamic target attainment across clinically relevant MIC thresholds.

In this prospective observational study, patients undergoing sleeve gastrectomy received cefazolin prophylaxis according to current guidelines (2 or 3 g intravenously). Plasma, dermis and adipose tissue samples were collected at incision (T0), 30 min (T30) and end of surgery (Tend). Total cefazolin concentrations were quantified using validated HPLC methods. Concentration-time profiles were analysed using linear mixed-effects models adjusted for age, BMI and creatinine clearance. Target attainment was evaluated at MIC thresholds of 2, 4 and 8 mg/L.

Dermis and plasma total cefazolin concentrations consistently exceeded all MIC thresholds in both dosing groups, whereas adipose tissue concentrations were more variable, with reduced attainment at higher MICs. Calculated unbound cefazolin concentrations demonstrated marked matrix-dependent differences: plasma unbound levels consistently exceeded all targets, dermal unbound concentrations increased significantly from T0 to Tend and adipose tissue unbound concentrations remained low across all time points. Increasing the dose from 2 to 3 g modestly improved total adipose tissue target attainment but did not substantially enhance unbound adipose tissue exposure. No surgical site infections occurred.

In patients with severe obesity, guideline-recommended cefazolin dosing provides adequate plasma and dermis exposure but fails to ensure reliable unbound adipose tissue concentrations. These findings highlight the limitations of plasma-based assessments and support tissue-informed, individualized prophylactic strategies in bariatric surgery.