Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial


Robert V. O'Toole, University of Maryland School of Medicine
Manjari Joshi, University of Maryland School of Medicine
Anthony R. Carlini, Johns Hopkins Bloomberg School of Public Health
Clinton K. Murray, San Antonio Military Medical Center, Texas
Lauren E. Allen, Johns Hopkins Bloomberg School of Public Health
Yanjie Huang, Johns Hopkins Bloomberg School of Public Health
Daniel O. Scharfstein, Johns Hopkins Bloomberg School of Public Health
Nathan N. O'Hara, University of Maryland School of Medicine
Joshua L. Gary, University of Texas Health Science Center at Houston
Michael J. Bosse, Carolinas Medical Center
Renan C. Castillo, Johns Hopkins Bloomberg School of Public Health
Julius A. Bishop, Stanford University
Michael J. Weaver, Harvard Medical School
Reza Firoozabadi, Harborview Medical Center
Joseph R. Hsu, Carolinas Medical Center
Madhav A. Karunakar, Carolinas Medical Center
Rachel B. Seymour, Carolinas Medical Center
Stephen H. Sims, Carolinas Medical Center
Christine Churchill, Carolinas Medical Center
Michael L. Brennan, Scott and White
Gabriela Gonzales, Scott and White
Rachel M. Reilly, Duke University
Robert D. Zura, Duke University
Cameron R. Howes, Duke University
Hassan R. Mir, Tampa General Hospital
Emily A. Wagstrom, Hennepin County Medical Center
Jerald Westberg, Hennepin County Medical Center
Greg E. Gaski, Indiana University-Purdue University Indianapolis
Laurence B. Kempton, Indiana University-Purdue University Indianapolis
Roman M. Natoli, Indiana University-Purdue University Indianapolis
Anthony T. Sorkin, Indiana University-Purdue University Indianapolis
Walter W. Virkus, Indiana University-Purdue University Indianapolis
Lauren C. Hill, Indiana University-Purdue University Indianapolis

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Publication Title

JAMA Surgery


Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P =.06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P =.02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P =.78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.



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