Increased Duration of Postop Antimicrobial Prophylaxis Tied to Adverse Events

Increasing the duration of antimicrobials postoperatively not only increases the risk of adverse events, but it does not reduce infection rates, according to a new study published in JAMA.

In a multicenter, national retrospective cohort study of 79,058 patients within the national Veterans Affairs health care system, investigators found that prolonging antimicrobial prophylaxis beyond the 24 hours recommended by national guidelines after cardiac, orthopedic total joint replacement, colorectal, and vascular procedures lead to an increased risk of Clostridium difficile (C diff) infection and higher odds of acute kidney injury (AKI).

“This is an important finding, because it suggests that antimicrobials can be stopped safely immediately after surgery and, in fact, patients may benefit from shorter durations of antimicrobial exposure,” Westyn Branch-Elliman, MD, MMSc, a clinician scientist at VA Boston Center for Healthcare, and an investigator on the study, told Contagion®.

Using data on type of surgical procedure, type and duration of antimicrobial prophylaxis (<24 hours, 24-<48 hours, 48-<72 hours, and >72 hours), and rates of C diff, AKI, and surgical-site infection, investigators adjusted for age, sex, race, diabetes, smoking status, American Society of Anesthesiologists score greater than 2, methicillin-resistant Staphylococcus aureus colonization, mupirocin, type of prophylaxis, and facility factors. Patients were predominately male (76,109 or 96.3%) and the mean age was 64.8 years.

Surgical-site infection was not demonstrated to be associated with duration of prophylaxis, but adjusted odds of AKI increased with each additional day of antimicrobial exposure (cardiac procedure: 24-<48 hours: adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.95-1.12; 48-<72 hours: aOR, 1.22; 95% CI, 1.08-1.39; >72 hours: aOR, 1.82; 95% CI, 1.54-2.16; noncardiac procedure: 24-<48 hours: aOR, 1.31; 95% CI, 1.21-1.42; 48-<72 hours: aOR, 1.72; 95% CI, 1.47-2.01; >72 hours: aOR, 1.79; 95% CI, 1.27-2.53).

C diff infection risks also increased in a similar duration-dependent fashion as AKI odds (24-<48 hours: aOR 1.08; 95% CI, 0.89-1.31; 48-<72 hours: aOR, 2.43; 95% CI, 1.80-3.27; >72 hours: aOR, 3.65; 95% CI, 2.40-5.53).

“The surprising aspect of this study was the clear dose-response relationship between every day of antimicrobial exposure and measurable patient harm,” Branch-Elliman said. “Clearly, preoperative antimicrobial prophylaxis is effective for reducing surgical-site infections, but we found that postoperative doses increase harm in a duration-dependent fashion. We hope that these findings can be used to improve clinical outcomes by maximizing benefits and minimizing harms associated with antimicrobial use.”

The receipt of vancomycin, in particular, was associated with an increased risk for AKI (cardiac procedure: aOR, 1.17; 95% CI, 1.10-1.25; noncardiac procedure: aOR, 1.21; 95% CI, 1.13-1.30).

Investigators are optimistic that the results of the study will encourage clinicians to view postoperative antimicrobial prophylaxis as an opportunity for antimicrobial stewardship.

“Limiting the duration of surgical prophylaxis is a rare opportunity to both improve clinical care and reduce medical costs, through reduced antimicrobial toxicity and reduced pharmaceutical costs,” Branch-Elliman told Contagion®. “We also hope that our findings can be used by antimicrobial stewardship programs to educate providers about the tangible harms of these medications and to facilitate more nuanced antimicrobial prescribing to balance both risks and benefits.”