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Original Investigation
April 24, 2019

Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events

Author Affiliations
  • 1Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts
  • 2VA Center for Healthcare Organization and Implementation Research (CHOIR), Boston, Massachusetts
  • 3Harvard Medical School, Boston, Massachusetts
  • 4Department of Surgery, VA Boston Healthcare System, Boston, Massachusetts
  • 5Boston University School of Medicine, Boston, Massachusetts
  • 6Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
  • 7Duke Clinical Research Institute (DCRI), Durham, North Carolina
JAMA Surg. 2019;154(7):590-598. doi:10.1001/jamasurg.2019.0569
Key Points

Question  How do the type and duration of surgical antimicrobial prophylaxis affect postoperative outcomes?

Findings  In this national cohort study including 79 058 patients undergoing surgical procedures in the VA health care system, increasing duration of surgical prophylaxis was not associated with additional reductions in surgical site infection but was associated with increases in acute kidney injury and Clostridium difficile infections. The type of regimen was also an important driver of postoperative adverse events; limiting the use of vancomycin may improve clinical outcomes.

Meaning  The risk of adverse events increases with each additional day of antimicrobial exposure.

Abstract

Importance  The benefits of antimicrobial prophylaxis are limited to the first 24 hours postoperatively. Little is known about the harms associated with continuing antimicrobial prophylaxis after skin closure.

Objective  To characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), and Clostridium difficile infection.

Design, Setting, and Participants  In this multicenter, national retrospective cohort study, all patients within the national Veterans Affairs health care system who underwent cardiac, orthopedic total joint replacement, colorectal, and vascular procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI from October 1, 2008, to September 30, 2013, were included. Data were analyzed using multivariable logistic regression, with adjustments for covariates determined a priori to be associated with the outcomes of interest. Data were analyzed from December 2016 to December 2018.

Exposures  Duration of postoperative antimicrobial prophylaxis (<24 hours, 24-<48 hours, 48-<72 hours, and ≥72 hours).

Main Outcomes and Measures  Surgical site infection, AKI, and C difficile infection.

Results  Of the 79 058 included patients, 76 109 (96.3%) were men, and the mean (SD) age was 64.8 (9.4) years. Among 79 058 surgical procedures in the cohort, all had SSI and C difficile outcome data available; 71 344 (90.2%) had AKI outcome data. After stratification by type of surgery and adjustment for age, sex, race, diabetes, smoking, American Society of Anesthesiologists score greater than 2, methicillin-resistant Staphylococcus aureus colonization, mupirocin, type of prophylaxis, and facility factors, SSI was not associated with duration of prophylaxis. Adjusted odds of AKI increased with each additional day of prophylaxis (cardiac procedure: 24-<48 hours: adjusted odds ratio [aOR], 1.03; 95% 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). The risk of postoperative C difficile infection demonstrated a similar duration-dependent association (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 unadjusted numbers needed to harm for AKI after 24 to less than 48 hours, 48 to less than 72 hours, and 72 hours or more of postoperative prophylaxis were 9, 6, and 4, respectively; and 2000, 90, and 50 for C difficile infection, respectively. Vancomycin receipt was also a significant risk factor for AKI (cardiac procedure: aOR, 1.17; 95% CI, 1.10-1.25; noncardiac procedure: aOR, 1.21; 95% CI, 1.13-1.30).

Conclusions and Relevance  Increasing duration of antimicrobial prophylaxis was associated with higher odds of AKI and C difficile infection in a duration-dependent fashion; extended duration did not lead to additional SSI reduction. These findings highlight the notion that every day matters and suggest that stewardship efforts to limit duration of prophylaxis have the potential to reduce adverse events without increasing SSI.

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