Early administration of prophylaxis does not significantly reduce surgical site infections

Early administration of surgical antimicrobial prophylaxis did not significantly reduce the risk for surgical site infection among adult patients compared with late administration before surgery, according to researchers in Switzerland.

Researchers added that the findings did not support any possible changes to current recommendations regarding surgical antimicrobial prophylaxis.

“Surgical site infections are the most common hospital-acquired infections in surgical patients, and have a substantial economic effect,” Walter P. Weber, MD, professor in the department of general surgery at University Hospital Basel, Switzerland, and colleagues wrote.

The researchers noted that WHO guidelines call for the administration of prophylaxis against surgical site infections less than 2 hours before incision but closer to 1 hour for antibiotics with a shorter half-life.

“Based on the available evidence, the joint guidelines from four large American societies concluded that the data are not sufficiently robust to recommend narrowing the 60-minute window,” Weber and colleagues wrote. “This research gap has been identified by the 2016 WHO guidelines, which call for a randomized controlled trial to clarify the optimum timing of surgical antimicrobial prophylaxis as a matter of high priority.”

Weber and colleagues performed a phase 3 randomized controlled superiority trial between Feb. 21, 2013, and Aug. 3, 2015, randomly assigning 5,580 patients to surgical antimicrobial prophylaxis either early, in the anesthesia room, (n = 2,798) or late, in the operating room (n = 2,782). All patients were treated at two centers  — either Basel or Aarau. Prophylaxis consisted of a single-shot, intravenous 1.5-g dose of cefuroxime, which in cases of colorectal surgery was combined with 500 mg of metronidazole. The primary endpoint was occurrence of surgical site infection within 30 days of surgery.

Median administration time for the early group was 42 minutes before incision, compared with 16 minutes in the late group. The overall 30-day follow-up rate was 88.8% (n = 4,596), and the overall surgical site infection rate was 5.1% (n = 234), researchers reported. Early administration of prophylaxis did not significantly reduce the risk for developing infection compared with late administration (OR = 0.93; 95% CI, 0.72-1.21), Weber and colleagues wrote.

"This was surprising for both the investigators who favored late and the ones who favored early administration. Based on our results, 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," Weber said. "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."

“The period before the first incision of an operative procedure is a crucial one,” Hilary Humphreys, MD, FRCPI, of the department of clinical microbiology at the Royal College of Surgeons in Ireland, wrote in an accompanying editorial. “However, it is incumbent on the surgical team, anesthetic team, pharmacist and antimicrobial stewardship program to ensure the that patient receives the first dose of antibiotics during this important 1-hour window. A more precise determination of time is probably not justified for this and similar surgical antimicrobial prophylaxis regimens, but for other drugs commonly used in prophylaxis treatment, data [are] required to inform and guide best clinical practice.”– by Andy Polhamus

Disclosure: Weber reports consulting fees from Takeda Pharmaceuticals for an unrelated trial, and grants from the Swiss National Science Foundation. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.