Narrow Window for Preoperative Antibiotics Does Not Reduce Infections

Administering antibiotics within 30 minutes prior to surgery did not improve rates of surgical site infection (SSI) compared with administering antibiotics within 60 minutes prior to surgery, according to a study published in The Lancet Infectious Diseases.¹

Surgical antimicrobial prophylaxis — often given as a single injection of a first or second generation cephalosporin — is most commonly administered within 60 minutes before surgery. However, practice guidelines by multiple organizations do not agree on the timing of surgical antimicrobial prophylaxis.¹ The 2016 World Health Organization (WHO) guidelines recommend antimicrobial prophylaxis within a 120-minute window, while other groups call for prophylaxis within 30 minutes prior to surgery.^2,3

Evidence is lacking, however, to support narrowing the window beyond 60 minutes, and the optimal timing for surgical antimicrobial prophylaxis is unknown. As a result, the 2016 WHO guidelines recognized that randomized controlled trials are needed to address this research gap.²

Researchers, led by Walter P. Weber, MD and Edin Mujagic, MD, from University Hospital Basel in Switzerland, evaluated the efficacy of SSI prevention with early administration (within 30 to 75 minutes) vs late administration (within 30 minutes) of cefuroxime prior to surgery.¹

In this phase 3 trial (ClinicalTrials.gov identifier NCT01790529), 5580 patients were randomly assigned to early or late surgical antimicrobial prophylaxis, which consisted of a single intravenous dose of cefuroxime 1.5 g administered over 2 to 5 minutes. A total of 5175 patients were included in the final analysis (early group, n=2589; late group, n=2586).¹

Patients in the early group and late group received antibiotic prophylaxis at a median of 42 minutes and 16 minutes before surgery, respectively.¹

Rates of SSI at 30 days, the primary outcome, were similar in both the early and late groups (4.9% vs 5.3%). The overall rate of SSI for the entire study population was 5.1%.¹

Early administration of surgical antimicrobial prophylaxis was not more effective than late administration at reducing the risk of SSI at 30 days (odds ratio, 0.93; 95% CI, 0.71-1.21; P =.601).¹

Hospital length-of-stay duration and 30-day mortality from any cause were also similar between the groups.¹

“The window of one hour before surgery can be considered [the] evidence-based standard for antibiotics with a short half-life, such as commonly used cephalosporins and penicillins,” Dr Weber concluded.

“Now efforts should be strengthened to actually deliver them within that time window in routine clinical practice. Clearly, these results cannot be applied to other drugs with vastly different pharmacokinetics, or patient populations with a high rate of antimicrobial resistance,” he added.

Dr Weber reports financial relationships with Takeda Pharmaceuticals International and Genomic Health.

Reference

1.   Weber WP, Mujagic E, Zwahlen M, et al. Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial [published online April 3, 2017] Lancet Infect Dis. doi:10.1016/S1473-3099(17)30176-7.

2.   World Health Organization (WHO). Global guidelines for the prevention of surgical site infection. http://apps.who.int/iris/bitstream/10665/250680/1/9789241549882-eng.pdf?ua=1. Published 2016. Accessed May 16, 2017.

3.   Alexander JW, Solomkin JS, Edwards MJ. Updated recommendations for control of surgical site infections. Ann Surg. 2011;253(6):1082-1093. doi: 10.1097/SLA.0b013e31821175f8.