Late administration of cephalosporins with a short half–life does not reduce the overall surgical site infection (SSI) rate, compared with the recommended 60 minutes before incision, researchers from Switzerland report.

"It was interesting to see that the exact timing of antibiotic prophylaxis within 1 hour before surgery had no significant impact on the risk of postoperative infection,” Dr. Walter P. Weber from University Hospital Basel told Reuters Health by email. “This is surprising for both the investigators who favor late and the ones who favor early administration.”

2016 World Health Organization guidelines for prevention of SSI call for a timing of less than 120 minutes before incision, but recommend that administration be closer to the incision time (<60 minutes) for antibiotics with a short half–life. Joint guidelines from four American societies concluded that the data are not sufficiently robust to recommend narrowing the 60–minute window.

Dr. Weber and colleagues investigated whether early administration of cefuroxime, a short–half–life cephalosporin, would be better than late administration before surgical incision for the prevention of SSI in colorectal surgery.

Median administration time was 42 minutes before incision in the early group (2,589 patients) and 16 minutes before incision in the late group (2,586 patients), the researchers report in The Lancet Infectious Diseases, online April 3.

The overall SSI rate in patients with a complete 30–day follow–up was 4.9% in the early group and 5.3% in the late group (P=0.601).

Results were similar in the intention–to–treat analysis and the as–treated analysis, and the rates of SSI did not differ between the two groups for all three types of SSI (superficial incisional infection, deep incisional infection and organ space infection).

“The window of 1 hour before surgery can be considered evidence–based standard for antibiotics with a short half–life, such as commonly used cephalosporins and penicillins,” Dr. Weber concluded. “The results discourage further attempts to study the narrowing of the 1–hour window before surgery for these antibiotics. Instead, efforts should be strengthened to actually deliver them within that time window in routine clinical practice.”

He added, “Future research may focus on the precise optimal timing for other antibiotics and the adjustment of dosing to body weight and duration of surgery.”

“The study investigated cefuroxime with or without metronidazole and consequently the findings are not applicable to other drugs with different pharmacokinetic properties,” writes Dr. Hilary Humphreys from Beaumont Hospital, in Dublin, Ireland, in an accompanying editorial.

“Giving surgical antibiotic prophylaxis (SAP) within 1 h of surgery should be feasible in most centers and is likely to provide adequate serum concentrations to optimize the prevention of SSI,” she notes. “However, it is possible that for specific types of surgery, a more precise timing regimen might be better, but to determine this would require large, complex multicenter studies.”

“A more precise determination of time is probably not justified for this and similar SAP regimens, but for other drugs commonly used in SAP treatment, data is required to inform and guide best clinical practice,” Dr. Humphreys concluded.

—Will Boggs, MD