Chlorhexidine gluconate vs povidone-iodine for surgical site infection prevention: a systematic review and meta-analysis stratified by surgery type, wound classification, antiseptic formulation, and country income, with meta-regression.

BACKGROUND

The comparative effectiveness of chlorhexidine gluconate (CHG) vs povidone-iodine (PVI) for preventing surgical site infections (SSIs) remains unclear across surgical types and resource settings. This study compared CHG and PVI overall and within key clinical subgroups.

METHODS

Five databases were searched through February 2025 for randomized controlled trials comparing CHG with PVI and reporting SSI outcomes. Random-effects models generated pooled odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS

Twenty-nine randomized clinical trials involving 35,317 patients were included. CHG significantly reduced superficial incisional SSIs (OR = 0.80; 95% CI: 0.67-0.95; P = 0.01; I2 = 18.4%), but not overall, deep, or organ/space infections; meta-regression indicated that patient age was a significant effect modifier. In caesarean sections, CHG lowered overall SSIs (OR = 0.64; 95% CI: 0.48-0.85), superficial incisional SSIs (OR = 0.65; 95% CI: 0.48-0.87), and deep incisional SSIs (OR = 0.41; 95% CI: 0.22-0.75). In abdominal surgery, CHG reduced only superficial incisional SSIs (OR = 0.68; 95% CI: 0.52-0.91). No significant differences were observed in gynaecologic, cardiothoracic, or orthopaedic procedures. By wound classification, CHG had no effect in clean surgery but reduced superficial incisional SSIs in clean-contaminated cases (OR = 0.65; 95% CI: 0.48-0.89). By income level, no differences were seen in high-income countries (HICs), whereas in low- and middle-income countries, CHG decreased overall SSIs (OR = 0.58; 95% CI: 0.46-0.74), superficial incisional SSIs (OR = 0.54; 95% CI: 0.38-0.76), and deep incisional SSIs (OR = 0.48; 95% CI: 0.25-0.92).

CONCLUSION

Alcohol-based CHG and alcohol-based PVI are comparably effective in most surgical settings. However, CHG demonstrates superior prevention of SSIs in caesarean, abdominal, and clean-contaminated surgeries, with the most substantial benefit in low- and middle-income settings. Broader use may be justified pending cost-effectiveness evaluation.