Target-controlled infusion vs. standard dosing of cefoxitin for surgical prophylaxis in colorectal surgery: a randomized clinical trial.

OBJECTIVES

To compare the incidence of surgical site infection (SSI) between patients receiving cefoxitin via target-controlled infusion (TCI) and those receiving standard dosing during colorectal surgery and to evaluate differences in intraoperative antibiotic exposure and postoperative safety outcomes.

METHODS

In this single-centre, parallel-arm randomized clinical trial, 2494 adults undergoing elective colorectal surgery between April 2022 and July 2025 were assigned to receive cefoxitin via TCI or the standard dosing method. The TCI group received cefoxitin through a pharmacokinetic model-driven infusion pump targeting a plasma concentration of 80 μg/mL until the end of surgery, whereas the standard group received 2 g every 2 hours up to 8 g. The primary endpoint was the incidence of SSI within 30 days after surgery. Secondary endpoints included intraoperative cumulative cefoxitin dose. Acute kidney injury was assessed as an additional safety endpoint.

RESULTS

No statistically significant difference in SSI incidence was detected between groups (TCI vs. standard: 69 of 1224 [5.6%] vs. 69 of 1233 [5.6%]; p 0.965; relative risk: 1.01; 95% CI: 0.73-1.39). The intraoperative cumulative cefoxitin dose was lower in the TCI group (median: 1.38 g; interquartile range: 1.15-1.71 g) than in the standard group (median: 2.00 g; interquartile range: 2.00-4.00 g; Mann-Whitney p < 0.001). The median difference was -0.62 g (95% CI: -0.65 to -0.59), representing ∼30% reduction for patients with median operative time (93 minutes) and body weight (62.5 kg). Pharmacokinetic simulations showed the dosing gap between regimens widened with longer operative duration and lower body weight. Acute kidney injury incidence did not differ significantly between groups (215 of 1224 [17.6%] vs. 193 of 1233 [15.7%]; p 0.223; relative risk: 1.12; 95% CI: 0.94-1.34).

CONCLUSIONS

In this randomized clinical trial, use of TCI of cefoxitin was not associated with a reduction in SSI compared with standard dosing, while resulting in lower intraoperative antibiotic exposure.