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Randomized Controlled Trial
. 2021 May 1;156(5):e207259.
doi: 10.1001/jamasurg.2020.7259. Epub 2021 May 12.

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

Major Extremity Trauma Research Consortium (METRC); Robert V O'Toole  1 , Manjari Joshi  2 , Anthony R Carlini  3 , Clinton K Murray  4 , Lauren E Allen  3 , Yanjie Huang  3 , Daniel O Scharfstein  3 , Nathan N O'Hara  1 , Joshua L Gary  5 , Michael J Bosse  6 , Renan C Castillo  3 , Julius A Bishop  7 , Michael J Weaver  8 , Reza Firoozabadi  9 , Joseph R Hsu  6 , Madhav A Karunakar  6 , Rachel B Seymour  6 , Stephen H Sims  6 , Christine Churchill  6 , Michael L Brennan  10 , Gabriela Gonzales  10 , Rachel M Reilly  11 , Robert D Zura  11 , Cameron R Howes  11 , Hassan R Mir  12 , Emily A Wagstrom  13 , Jerald Westberg  13 , Greg E Gaski  14 , Laurence B Kempton  14 , Roman M Natoli  14 , Anthony T Sorkin  14 , Walter W Virkus  14 , Lauren C Hill  14 , Robert A Hymes  15 , Michael Holzman  15 , A Stephen Malekzadeh  15 , Jeff E Schulman  15 , Lolita Ramsey  15 , Jaslynn A N Cuff  15 , Sharon Haaser  15 , Greg M Osgood  16 , Babar Shafiq  16 , Vaishali Laljani  16 , Olivia C Lee  17 , Peter C Krause  17 , Cara J Rowe  17 , Colette L Hilliard  17 , Massimo Max Morandi  18 , Angela Mullins  18 , Timothy S Achor  5 , Andrew M Choo  5 , John W Munz  5 , Sterling J Boutte  5 , Heather A Vallier  19 , Mary A Breslin  19 , H Michael Frisch  20 , Adam M Kaufman  20 , Thomas M Large  20 , C Michael LeCroy  20 , Christina Riggsbee  21 , Christopher S Smith  22 , Colin V Crickard  22 , Laura S Phieffer  23 , Elizabeth Sheridan  23 , Clifford B Jones  24 , Debra L Sietsema  24 , J Spence Reid  25 , Kathy Ringenbach  25 , Roman Hayda  26 , Andrew R Evans  26 , M J Crisco  26 , Jessica C Rivera  27 , Patrick M Osborn  27 , Joseph Kimmel  27 , Stanislaw P Stawicki  28 , Chinenye O Nwachuku  29 , Thomas R Wojda  30 , Saqib Rehman  31 , Joanne M Donnelly  31 , Cyrus Caroom  32 , Mark D Jenkins  32 , Christina L Boulton  1 , Timothy G Costales  1 , Christopher T LeBrun  1 , Theodore T Manson  1 , Daniel C Mascarenhas  1 , Jason W Nascone  1 , Andrew N Pollak  1 , Marcus F Sciadini  1 , Gerard P Slobogean  1 , Peter Z Berger  1 , Daniel W Connelly  1 , Yasmin Degani  1 , Andrea L Howe  1 , Dimitrius P Marinos  1 , Ryan N Montalvo  1 , G Bradley Reahl  1 , Carrie D Schoonover  1 , Lisa K Schroder  33 , Sandy Vang  33 , Patrick F Bergin  34 , Matt L Graves  34 , George V Russell  34 , Clay A Spitler  34 , Josie M Hydrick  34 , David Teague  35 , William Ertl  35 , Lindsay E Hickerson  35 , Gele B Moloney  36 , John C Weinlein  37 , Boris A Zelle  38 , Animesh Agarwal  38 , Ravi A Karia  38 , Ashoke K Sathy  39 , Brigham Au  39 , Medardo Maroto  39 , Drew Sanders  39 , Thomas F Higgins  40 , Justin M Haller  40 , David L Rothberg  40 , David B Weiss  41 , Seth R Yarboro  41 , Eric D McVey  41 , Veronica Lester-Ballard  41 , David Goodspeed  42 , Gerald J Lang  42 , Paul S Whiting  42 , Alexander B Siy  42 , William T Obremskey  43 , A Alex Jahangir  43 , Basem Attum  43 , Eduardo J Burgos  43 , Cesar S Molina  43 , Andres Rodriguez-Buitrago  43 , Vamshi Gajari  43 , Karen M Trochez  43 , Jason J Halvorson  44 , Anna N Miller  44 , James Brett Goodman  44 , Martha B Holden  44 , Christopher M McAndrew  45 , Michael J Gardner  45 , William M Ricci  45 , Amanda Spraggs-Hughes  45 , Susan C Collins  3 , Tara J Taylor  3 , Mary Zadnik  3
Affiliations
Randomized Controlled Trial

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

Major Extremity Trauma Research Consortium (METRC) et al. JAMA Surg. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr O’Toole reported receiving grants from the U.S. Department of Defense (DOD) Congressionally Directed Medical Research Program during the conduct of the study and personal fees from Smith & Nephew, stock options from Imagen, personal fees and royalties from Lincotek, and personal fees from Zimmer outside the submitted work. Dr Joshi reported receiving grants from the DOD during the conduct of the study and grants from the DOD and the Patient-Centered Outcomes Research Institute (PRORP) outside the submitted work. Dr Carlini reported receiving grants from the DOD during the conduct of the study. Dr Scharfstein reported receiving grants from the DOD during the conduct of the study. Dr O’Hara reported receiving grants from the DOD during the conduct of the study. Dr Gary reported receiving grants from the DOD during the conduct of the study and being a paid presenter for Smith & Nephew and receiving honoria for teaching and personal fees from Stryker outside the submitted work. Dr Bosse reported receiving grants from the DOD during the conduct of the study. Dr Castillo reported receiving grants from the PRORP and DOD during the conduct of the study. Dr Bishop reported receiving personal fees from Stryker, KCI, Innomed, and Globus outside the submitted work. Dr Weaver reported receiving personal fees from OsteoCentric and royalties for fracture implants outside the submitted work. Dr Firoozabadi reported being a paid consultant for Smith & Nephew Consulting outside the submitted work. Dr Hsu reported receiving personal fees from Smith & Nephew, consulting and personal fees from Globus Medical consulting, personal fees from DePuy Synthes, and honoraria and personal fees from Stryker outside the submitted work. Dr Karunakar reported receiving grants from the DOD during the conduct of the study. Dr Seymour reported receiving grants from the DOD during the conduct of the study. Dr Sims reported receiving grants from the DOD during the conduct of the study. Dr Churchill reported receiving grants from Atrium Health Carolinas Medical Center during the conduct of the study. Dr Zura reported receiving personal fees from Bioventus and being a paid consultant for OsteoCentric Consulting outside the submitted work. Dr Wagstrom reported receiving grants from the DOD during the conduct of the study and personal fees from Stryker outside the submitted work. Dr Westberg reported receiving grants from Johns Hopkins via the DOD during the conduct of the study. Dr Kempton reported receiving grants from METRC consortium funding during the conduct of the study. Dr Sorkin reported receiving personal fees from Stryker outside the submitted work. Dr Virkus reported receiving grants from the Indiana University School of Medicine during the conduct of the study and grants from the DOD outside the submitted work. Dr Holzman reported receiving personal fees from Johnson & Johnson outside the submitted work. Dr Schulman reported receiving personal fees from Stryker outside the submitted work. Dr Ramsey reported receiving other from METRC funds during the conduct of the study. Dr Shafiq reported receiving nonfinancial support from DePuy Synthes and other from Bone Foam Board outside the submitted work. Dr Achor reported receiving personal fees from DePuy Synthes, personal fees from Stryker, and personal fees from Globus outside the submitted work. Dr Choo reported receiving personal fees from Synthes outside the submitted work. Dr Vallier reported receiving grants from the DOD during the conduct of the study; and grants from the PRORP, DOD, and the Orthopaedic Trauma Association (OTA) outside the submitted work. Dr Phieffer reported receiving personal fees from DePuy Synthes Consulting outside the submitted work. Dr Sietsema reported receiving grants from Johns Hopkins the DOD Subaward during the conduct of the study. Dr Reid reported receiving other from the DOD and financial support through the METRC consortium, which provided per–enrolled patient institutional support for this study during the conduct of the study; and personal and consulting fees for product development from DePuy Synthes and consulting fees from Smith & Nephew outside the submitted work. Dr Rehman reported receiving consulting fees from Globus Medical. Dr Costales reported receiving grants from the DOD during the conduct of the study. Dr Manson reported receiving grants from METRC during the conduct of the study. Dr Nascone reported receiving personal and consulting fees from Smith & Nephew, Zimmer, and Aona Travel; honoraria and personal fees from Coorstek Royalties; personal fees and royalties from DePuy Synthes; and Imagen stock options for consulting. Dr Pollak reported receiving grants from the DOD during the conduct of the study and personal fees from Globus and Zimmer outside the submitted work. Dr Slobogean reported receiving grants from the DOD during the conduct of the study and personal fees from Bayer AG outside the submitted work. Dr Schroder reported receiving grants from METRC funding during the conduct of the study; personal fees from Johnson & Johnson and DePuy Synthes, and consulting and personal fees from Exactech, and consulting fees outside the submitted work. Dr Vang reported receiving grants from the DOD during the conduct of the study. Dr Bergin reported receiving personal fees from Synthes outside the submitted work. Dr Spitler reported receiving personal fees from DePuy Synthes, personal fees from the Journal of Bone and Joint Surgery, and grants from Stryker outside the submitted work. Dr Teague reported receiving grants from METRC during the conduct of the study and being a board member of the OTA. Dr Moloney reported receiving grants from METRC during the conduct of the study. Dr Zelle reported receiving personal fees and grants from 3M, grants and personal fees from DePuy Synthes, and personal fees from AO North America outside the submitted work. Dr Sanders reported receiving educational fees from Smith & Nephew. Dr Higgins reported receiving personal fees from DePuy Synthes and personal fees from Globus and Imagen outside the submitted work and holding stock from Orthogrid, NT nPhase, and OsteoCentric. Dr Haller reported receiving personal fees from Stryker and NewClip Technics and grants from the OTA and the Arthritis Foundation outside the submitted work. Dr Weiss reported receiving grants from Johns Hopkins University/METRC during the conduct of the study and personal fees from DePuy Synthes, GlobusMedical, and Elsevier Publishing outside the submitted work. Dr Yarboro reported receiving intellectual property royalties from Advanced Orthopaedic Solutions and having a royalty agreement for product development outside the submitted work. Dr Goodspeed reported receiving honoria for teaching for AO North America. Dr Lang reported receiving grants from METRC during the conduct of the study. Dr Halvorson reported receiving grants from the DOD during the conduct of the study, being a paid speaker for AO North America, and being a paid consultant for Smith & Nephew. Dr McAndrew reported receiving grants from the DOD METRC during the conduct of the study; and grants from Zimmer Biomet outside the submitted work. Dr Ricci reported being a part owner of CableFix LLC; an investor with McGinley Orthopaedic Innovations; the owner of Primo MC LLC; and an investor with HS2; receiving royalties from MicroPort, Smith & Nephew, and Wolters-Kluwer; and being a designer with OsteoCentric outside the submitted work. Dr Collins reported receiving institutional grants from the DOD during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Flowchart
ITT indicates intention to treat.
See this image and copyright information in PMC

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