Increasing Duration of Surgical Prophylaxis Does Not Decrease Odds of SSI

Instead, increasing duration of postoperative antimicrobial prophylaxis is associated with higher odds of acute kidney injury and C diff infection in a dose-dependent manner.

Surgical site infections are among the most common causes of health care-associated infections, and the human and financial costs of treating them continue to increase.

In fact, the US Centers for Disease Control and Prevention (CDC) estimate that there are 157,500 surgical site infections reported in the United States each year, and they account for $3.2 billion in attributable cost per year in acute care hospitals.

To prevent these infections, health care providers have turned to the use of antimicrobial prophylaxis. New research presented at ID Week 2018 emphasized that the benefits of surgical antimicrobial prophylaxis are limited to the first 24 hours post-operation, and prolonging prophylaxis is associated with increased likelihood of acute kidney injuries and Clostridium difficile infections.

In an oral abstract presentation, Judith M. Strymish, MD, assistant professor of medicine, VA Boston Healthcare System and Harvard Medical School, stressed that when it comes to surgical prophylaxis “every day matters.”

Multi-society prophylaxis guidelines recommend that antimicrobials be initiated within 1 hour prior to surgery and discontinued within 24 hours for most procedures. These recommendations were also based on data indicating that increasing duration of prophylaxis will not lead to additional surgical site infection risk reduction; however, not much is known about the harms are in doing so.

As such, Dr. Strymish and her team set out to characterize the relationship between duration of prophylaxis and postoperative outcomes, including surgical site infection, acute kidney injury, and C diff infections. To do this, they evaluated surgical patients who were entered into the VA pre- and post-operative quality databases which include information pertaining to the type and duration of prophylaxis as well as patient outcomes.

From October 1, 2008, to September 30, 2013, the investigators analyzed data on all patients who underwent cardiac, orthopedic total joint, vascular, and colorectal procedures and who had received planned manual review for type and duration of prophylaxis.

The team’s exposure variables of interest were the type and duration of prophylaxis, which were divided into several mutually-exclusive groups of antibiotics, with a single β-lactam as the referent group. Other groups included vancomycin and aminoglycoside, aminoglycoside alone or in combination, vancomycin alone or in combination, and an “other” category which consisted mostly of clindamycin or fluoroquinolone.

The duration of prophylaxis was divided into groups of “less than 24 hours,” “24 to 48 hours,” “48 to 72 hours,” and “greater than 72 hours;” “less than 24 hours” served as the referent group. The investigators then used logistic regression analysis to assess the impact of type and duration of prophylaxis on outcomes. The surgical site infection outcome was a 30-day endpoint, according to Dr. Strymish, while acute kidney injury was a 7-day endpoint and C diff infection was a 90-day endpoint. Risk factors for each syndrome were selected a priori.

Out of 79,092 total patients, all patients had surgical site infection and C diff outcomes available; 67,729 had acute kidney injury outcomes available. After stratifying via type of surgery and then adjusting for age, sex, race, diabetes, smoking, pre-operative methicillin-resistant Staphylococcus aureus colonization status, mupirocin receipt, and type of prophylaxis, the investigators did not find a significant link between surgical site infection and duration of prophylaxis (ie, longer treatment durations did not lead to additional surgical site infection reduction.

In terms of the risk of acute kidney injury in their adjusted models, Dr. Strymish stressed that there were 2 key take-home points. “The first is about the impact of antimicrobial choice on acute kidney injury and the second is about duration,” she said.

Risk of acute kidney injury increased significantly in patients who received vancomycin as their agent, she said. There was an odds increase of about 22% in both cardiac and non-cardiac surgeries, with the risk being very similar in both groups. In the non-cardiac surgery—which consisted of the majority of the study cohort (~50,000 patients)—there was an increased risk which appeared to be synergistic if patients received vancomycin and an aminoglycoside.

“In terms of antimicrobial duration, there was an increased risk of acute kidney injury with every additional day of prophylaxis in the cardiac surgery group,” shared Dr. Strymish. “And so, the odds increased from about 14% for 24 to 48 hours, to approximately 30% in 48 to 72 hours, then doubled in patients who received greater than 72 hours of prophylaxis.”

Similar results were seen when it came to C diff infections. “There was a 7% increase in odds for 24 to less than 48 hours. The odds then went up to 140% for 48 to 72 hours, and then 265% for greater than 72 hours,” she said. “There was also impact of antimicrobial choice on the rates of post-operative C diff infections and this was predominately driven by clindamycin and fluoroquinolones.”

Dr. Strymish and her team concluded that increasing the duration of postoperative prophylaxis was associated with higher likelihood of acute kidney injury and C diff infection in a dose-dependent manner, and additional days of treatment are not linked with reduced odds of SSI. Risk of acute kidney injury increases with type and duration of prophylaxis, with regimens that contain vancomycin at particularly high risk.

“It is our hope that these findings can be used to ‘choose wisely’ and reduce unnecessary exposures,” Dr. Strymish concluded, “and to counsel both providers and surgeons about the best use of antimicrobials. In summary, every day really does matter.”