By Thomas Rosenthal

Continuing antimicrobial regimens after surgery does not decrease surgical site infections but may increase acute kidney injuries and Clostridioides difficile infections, according to a new study.

The optimum time to administer antimicrobial surgical prophylaxis is an hour before the procedure and during the surgery, whereas the best time to stop the regimen is within 24 hours after skin closure, said Westyn Branch-Elliman, MD, MMSc, an assistant professor of medicine at Harvard Medical School, in Boston, and the lead author of the study.

The leading current surgical prophylaxis guidelines recommend antimicrobials be ceased within 24 hours after incisions for most operations, although multisociety guidelines recommend that regimens can continue up to 48 hours for cardiac procedures, Dr. Branch-Elliman said.

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This multicenter, national retrospective study of 79,058 veterans who underwent cardiac, vascular, colorectal and orthopedic surgeries in the Veterans Health Administration health care system from October 2008 to September 2013 sought to identify the optimal duration for surgical antimicrobial prophylaxis, Dr. Branch-Elliman said (JAMA Surg 2019;154[7]:590-598).

The study’s “data suggest that the routine practice of continuing antimicrobial prophylaxis after skin closure should be discontinued, given that results are consistent with a lack of benefit and demonstration of preventable harm with longer regimens,” she wrote.

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Not only are longer durations of prophylaxis associated with increases in acute kidney injury (AKI) and C. difficile infection, but “combination regimens may have an additive effect on AKI risk,” the researchers concluded. Vancomycin alone or in combination is associated with increased odds of AKI compared with other types of medications used for surgical prophylaxis.

“Choice of surgical prophylaxis impacts the incidence of ssI and other adverse events,” Dr. Branch-Elliman wrote. “These data should be used to inform policy surrounding surgical prophylaxis and may have broader implications for antimicrobial stewardship programs aiming to reduce harms associated with unnecessary antimicrobial exposures.”

When it comes to antimicrobial surgical prophylaxis, Dr. Branch-Elliman told General Surgery News, “Every day—and every dose—matters.”

“This is an important study that details the unintentional harm that can occur when overprescribing antibiotics to surgical patients,” said Mary T. Hawn, MD, MPH, in the Department of Surgery at Stanford University, in California, who was not associated with the study but was asked to comment.

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“We often think of perioperative antibiotics as ‘can’t hurt, might help therapy’ in reducing surgical infections,” Dr. Hawn said. “This study nicely demonstrates that more antibiotics are not only not better care, but can result in worse outcomes for surgical patients.”

In an invited commentary (JAMA Surg 2019;154[7]:598-599) on Dr. Branch-Elliman’s article in JAMA Surgery, Dr. Hawn and her Stanford colleague Lisa Marie Knowlton, MD, MPH, wrote, “While the goal of perioperative antimicrobial prophylaxis is to prevent ssIs, antibiotic misuse is widespread and can have deleterious effects.

“The unintended consequences of prolonged therapy include drug toxicity, the emergence of Clostridium difficile infections and antimicrobial resistance,” they reminded surgeons.

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For the 21,396 veterans in Dr. Branch-Elliman’s study who underwent cardiac surgery, the odds of AKI did not increase significantly (3.2%) after they received antimicrobial prophylaxis 24 to 48 hours after the procedure, the researchers said. However, the risk for AKI jumped significantly (22.3%) after 48 to 72 hours, and even more (82%) after 72 hours of antimicrobial therapy, they found.

For the 8,177 vascular, 10,810 colorectal and 38,675 orthopedic total joint surgeries in the study, continuation of antimicrobial surgical prophylaxis for up to 24 hours past skin closure led to significant daily risk increases of AKI after 24 to 48 hours (31%), 48 to 72 hours (71.5%) and 72 hours (79.2%).

“This study’s findings present an important opportunity to reduce the incidence of AKI, as well as irreversible kidney failure, following major surgery,” said Kerry Willis, PhD, the chief scientific officer of the National Kidney Foundation, in New York City, who was asked to comment on Dr. Branch-Elliman’s study.

“Once AKI occurs, even patients who have complete recovery of kidney function are at increased risk of progressive kidney disease, and AKI in patients with chronic kidney disease often accelerates progression to kidney failure,” Dr. Willis said. “It is especially encouraging that reducing the dose of antibiotics postoperatively to minimize AKI risk does not increase ssI. We hope these observations will stimulate the reexamination of surgical prophylaxis protocols and further research to reduce unnecessary risks.”

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In Dr. Branch-Elliman’s study, the risk for C. difficile increased 7.8% for patients who underwent all surgeries and were continued on an antimicrobial prophylaxis regimen for longer than 24 hours, but this was not significant. However, the increase of C. difficile was 142% after 48 to 72 hours and by 265% after more than 72 hours of antimicrobial prophylaxis, the study found.

Dr. Branch-Elliman said the type of prophylaxis affected both AKI and C. difficile. “Use of vancomycin for surgical prophylaxis, alone or in combination, was independently associated with increased odds of AKI following both cardiac (17.1%) and non-cardiac surgeries (21.0%),” the researchers found.

“Rates of C. difficile appeared to be higher after other types of antibiotics were used for surgical prophylaxis, particularly clindamycin and fluoroquinolones,” Dr. Branch-Elliman said. “Both types of antibiotics have been associated with particularly high risk of C. difficile in other studies.”

Dr. Branch-Elliman acknowledged that surgeons’ administering antimicrobial regimens past skin closure is an honest effort to prevent ssIs but said she hoped her study’s findings would help inform clinicians of the daily risk of continuing antimicrobial exposure. She also said the more precise quantification of the risks from continued exposure would assist antimicrobial stewardship programs.

“The study’s findings suggest that strategies that limit duration of exposure to pre-incision and intraoperative doses only have the potential to maximize the benefits of reducing surgical site infections while minimizing the harms of acute kidney injury and C. difficile infections,” she said.