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Publication Briefs

Risk of Adverse Events Increases with Each Additional Day of Prophylactic Antimicrobial Exposure following Surgery

National guidelines recommend surgical antimicrobial prophylaxis be initiated within 1 hour prior to incision and discontinued within 24 hours post-operatively for most procedures – and within 48 hours for cardiac surgery. Limited data are available regarding the risks of prolonged prophylaxis regimens. This national retrospective VA study sought to characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), and Clostridium difficile infection among all Veterans (n=79,058) undergoing major cardiac, orthopedic total joint replacement, colorectal, and vascular procedures between October 2008 and September 2013. Outcomes included 30-day SSI, 7-day incidence of AKI, and 90-day Clostridium difficile infection. Covariates included the duration and type of antimicrobial prophylaxis, i.e., β-lactam, vancomycin, IV aminoglycoside, and any other systemic antimicrobial (alone or in combination). Investigators also controlled for individual surgical site infection risk factors and facility quality metrics.


  • Surgical prophylaxis reduces infections when used appropriately. Durations lasting for greater than 24 hours increase the incidence of adverse events, such as acute kidney injury and C. difficile, but do not reduce surgical site infections. Risk of harm increases with each additional day of antimicrobial exposure.
  • The choice of surgical prophylaxis affects the incidence of SSI and other adverse events. For example, the use of vancomycin was independently associated with increased odds of AKI following both cardiac procedures (17%) and non-cardiac procedures (21%).


  • Every day matters. Findings can be used by antimicrobial stewardship programs to promote discontinuation of antimicrobials when they are no longer clinically necessary and to inform policy surrounding surgical prophylaxis. Potential future improvements include limiting the duration of surgical prophylaxis to perioperative doses only and limiting the use of vancomycin to patients at high risk for MRSA.


  • Investigators focused on specific measurable adverse outcomes, thus other adverse effects were not captured.
  • Because this study was retrospective, we cannot exclude the possibility that some unmeasured factor contributed to the outcome. Data, however, were collected as part of an organized quality review process that includes a more complete set of clinical data than most retrospective studies. Prospective studies comparing different lengths of prophylaxis are not likely to be feasible or ethical.

This study was partly funded by HSR&D (IIR 12-103). All authors except Dr. Wyatt are part of HSR&D's Center for Healthcare Organization and Implementation Research (CHOIR), Boston, MA.

PubMed Logo Branch-Elliman W, O’Brien W, Strymish J, Itani K, Wyatt C, and Gupta K. Association of Duration and Type of Surgical Prophylaxis with Antimicrobial-Associated Adverse Events. JAMA Surgery. April 24, 2019. Epub ahead of print.

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HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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