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SYSTEMATIC REVIEW article

Front. Med.

Sec. Infectious Diseases: Pathogenesis and Therapy

Chlorhexidine versus Povidone-Iodine for Surgical Site Infection Prevention: An Updated Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Provisionally accepted
Shengyi  YangShengyi YangZhenwei  LiZhenwei LiFeiyu  WuFeiyu WuLiyuan  SunLiyuan SunYulu  HeYulu HeShengyi  YangShengyi Yang*
  • The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China

The final, formatted version of the article will be published soon.

Background: Chlorhexidine (CHX) and povidone-iodine (PVI) are the most commonly used antiseptic agents for preoperative skin preparation to prevent surgical site infections (SSIs). This meta-analysis aimed to determine the superior agent between them for SSI prevention. Methods: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of electronic databases was performed from inception to May 1, 2025, to identify relevant randomized controlled trials (RCTs). Heterogeneity was assessed using the Chi-squared (Q) test and I2 statistic. A random-effects model was applied when significant heterogeneity was present. The robustness of the findings was evaluated using trial sequential analysis (TSA) with a random-effects model. All statistical analyses were performed using Review Manager. Results: A total of 32 high-quality RCTs, involving 29,748 participants, were included. The pooled analysis using a random-effects model demonstrated that CHX was significantly more effective than PVI in preventing SSIs (RR = 0.83, 95% CI 0.72-0.95, P = 0.009). Subgroup analysis by wound classification revealed that CHX was superior to PVI in clean-contaminated surgeries (11 RCTs; RR = 0.75, 95% CI 0.62-0.92, P = 0.004), but no significant difference was observed in clean surgeries (20 RCTs; RR = 0.90, 95% CI 0.67-1.20, P = 0.46). Further stratification by SSI type indicated that CHX significantly reduced the risk of superficial incisional SSIs (18 RCTs; RR = 0.82, 95% CI 0.69-0.98, P = 0.03), but not deep incisional SSIs (16 RCTs; RR = 0.95, 95% CI 0.76-1.18, P = 0.63) or organ-space SSIs (11 RCTs; RR = 1.13, 95% CI 0.89-1.42, P = 0.32). Additionally, CHX was associated with a significantly lower risk of bacterial decolonization (RR = 0.38, 95% CI 0.26-0.57, P < 0.001) and febrile episodes (RR = 0.57, 95% CI 0.35-0.92, P = 0.02) compared to PVI. The TSA confirmed the robustness of these findings, indicating that the cumulative evidence was sufficient and conclusive. Conclusions: CHX-based antiseptics are more effective than PVI-based ones in preventing overall SSIs, particularly in clean-contaminated procedures.

Keywords: Chlorhexidine, Povidone-Iodine, Surgical site infection, Meta-analysis, randomised controlled trials

Received: 06 Jun 2025; Accepted: 31 Oct 2025.

Copyright: © 2025 Yang, Li, Wu, Sun, He and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Shengyi Yang, 220203857@seu.edu.cn

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