Antimicrobial resistance (AMR) is a substantial threat to modern medicine that contributes to more than five million deaths globally each year¹. In response to this threat, the perioperative use of antibiotics, which helps reduce the risk of surgical site infection (SSI), has become more targeted and evidence-based. Surgical antibiotic prophylaxis (SAP) accounts for roughly one in six in-hospital antibiotic prescriptions worldwide, and its misuse represents a significant and largely preventable driver of resistance². How antibiotics are selected, timed, and discontinued in the perioperative setting has direct implications not only for individual patients but for the broader landscape of antimicrobial resistance.
The rationale for surgical antibiotic prophylaxis is well established: administering an effective antibiotic before bacterial contamination occurs during surgery reduces the risk of surgical site infection. However, adherence to best principles is subject to improvement. The World Health Organization’s AWaRe antibiotic book recommends that prophylaxis be administered no more than 120 minutes before incision—as a single dose in most cases—and that it be discontinued immediately after wound closure¹. These recommendations are informed by well-established pharmacodynamic and clinical evidence bases.
The importance of timing was rigorously examined in a systematic review of 14 observational studies encompassing 54,552 patients. Meta-analysis found that administering SAP more than 120 minutes before incision was associated with a fivefold increase in SSI risk compared with administration within that window (OR 5.26; 95% CI 3.29–8.39), while administration after first incision nearly doubled the risk (OR 1.89; 95% CI 1.05–3.40)³. Crucially, no significant difference in SSI rates was found when comparing administration in the 120–60 minute window versus the final 60 minutes before incision, providing strong support for facilities with stricter protocols to allow SAP administration within the larger 120-minute window³.
Research confirms that the key to successful SAP administration is having adequate tissue antibiotic concentrations at the moment of incision and maintaining these concentrations throughout the procedure. One study of patients undergoing elective colorectal study examined intraoperative gentamicin concentrations. Their analysis identified the antibiotic concentration at the time of wound closure as an independent risk factor for SSI, with a critical threshold of 1.6 mg/L below which infection rates rose sharply⁴.
The question of postoperative continuation of antibiotics is one that has been central to efforts to combat antimicrobial resistance. Data pooled from 52 randomized controlled trials involving 19,273 patients showed no benefit to continuing antibiotic prophylaxis after surgery when best practice standards were followed (RR 1.04; 95% CI 0.85–1.27)². In trials where timing and intraoperative redosing were properly standardized, postoperative continuation conferred no reduction in SSI rates whatsoever. Prolonged prophylaxis was instead associated with increased adverse events, higher costs, and greater risk of Clostridioides difficile infection².
Evidence-based perioperative antibiotic use centers on administering the right drug at the right time and in the right dose while ceasing administration promptly after closure to balance patient safety with best practices against antimicrobial resistance. The WHO AWaRe framework—which classifies antibiotics by their resistance potential and recommends narrow-spectrum “Access” agents such as cefazolin as first-line prophylaxis for most surgical procedures—provides a practical and evidence-based structure for achieving this¹.
References
- World Health Organization. The WHO AWaRe (Access, Watch, Reserve) Antibiotic Book. Geneva: WHO; 2022. https://www.who.int/publications/i/item/9789240062382
- de Jonge, S. W. et al. Effect of postoperative continuation of antibiotic prophylaxis on the incidence of surgical site infection: a systematic review and meta-analysis. Lancet Infect. Dis.20, 1182–1192 (2020). https://doi.org/10.1016/S1473-3099(20)30084-0
- de Jonge, S. W. et al. Timing of preoperative antibiotic prophylaxis in 54,552 patients and the risk of surgical site infection: a systematic review and meta-analysis. Medicine96, e6903 (2017). https://doi.org/10.1097/MD.0000000000006903
- Zelenitsky, S. A., Ariano, R. E., Harding, G. K. M. & Silverman, R. E. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob. Agents Chemother.46, 3026–3030 (2002). https://doi.org/10.1128/AAC.46.9.3026-3030.2002
