Background

The use of preoperative surgical antibiotic prophylaxis is effective in preventing surgical site infection. However, obesity, a major risk factor for surgical site infection, affects the pharmacokinetics and effectiveness of surgical antibiotic prophylaxis. Evidence for weight-based surgical antibiotic prophylaxis in patients with obesity is inconsistent.

Methods

MEDLINE (PubMed), Embase, CENTRAL, and CINAHL were searched up to 21 October 2025 for eligible studies on weight-based surgical antibiotic prophylaxis and surgical site infection. This systematic review and random-effects meta-analysis compared weight-based dosing of surgical antibiotic prophylaxis with standard surgical antibiotic prophylaxis, in terms of surgical site infection rates in patients with obesity. The certainty of evidence was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials, the Risk Of Bias in Non-randomized Studies—of Interventions tool for observational studies, and Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

Of 2782 potentially relevant articles, 33 studies were eligible (3 randomized clinical trials, 30 observational). A total of 99 211 patients were included, of whom 2362 (2.4%) developed a surgical site infection. Risk of bias varied from ‘low’ to ‘some concerns’ in randomized trials, and ‘some concerns’ to ‘serious’ in observational studies. Meta-analysis of 3 randomized trials with only 1 surgical site infection among 103 patients (1.0%) showed no significant reduction in surgical site infection rates in patients receiving weight-based dosing of cefazolin versus standard dosing (risk difference 2.02 (95% confidence interval −3.15 to 7.19)%). Meta-analysis of 6 observational studies with 45 554 patients and 610 surgical site infections (1.3%) showed significantly reduced surgical site infection rates in patients receiving weight-based dosing of cefazolin versus standard dosing (risk difference −1.93 (−2.84 to −1.02)%), with most studies focusing on orthopaedic surgery. GRADE assessments showed very low certainty of evidence.

Conclusion

Based on observational data, the use of weight-based dosing of surgical antibiotic prophylaxis may reduce the risk of surgical site infection in patients with obesity compared with standard dosing, but the existing evidence is very uncertain.