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

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

doi:10.1001/jamasurg.2020.7259

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English
Journal	JAMA Surgery
Volume	156
Issue number	5
DOIs	https://doi.org/10.1001/jamasurg.2020.7259
State	Published - May 2021
Externally published	Yes

Access to Document

10.1001/jamasurg.2020.7259

Cite this

O'Toole, R. V., Joshi, M., Carlini, A. R., Murray, C. K., Allen, L. E., Huang, Y., Scharfstein, D. O., O'Hara, N. N., Gary, J. L., Bosse, M. J., Castillo, R. C., Bishop, J. A., Weaver, M. J., Firoozabadi, R., Hsu, J. R., Karunakar, M. A., Seymour, R. B., Sims, S. H., Churchill, C., ... Zadnik, M. (2021). Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial. JAMA Surgery, 156(5). https://doi.org/10.1001/jamasurg.2020.7259

@article{7d097606abd04979b5ea98c5395c3c36,

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

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.",

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

note = "Funding Information: (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{\textquoteright}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 Funding Information: Funding/Support: The study was funded by grant W81XWH-10-2-0134 from the DOD{\textquoteright}s Congressionally Directed Medical Research Program (Drs O{\textquoteright}Toole, Castillo, and Carlini). Publisher Copyright: {\textcopyright} 2021 American Medical Association. All rights reserved.",

year = "2021",

month = may,

doi = "10.1001/jamasurg.2020.7259",

language = "English",

volume = "156",

journal = "JAMA Surgery",

issn = "2168-6254",

number = "5",

}

O'Toole, RV, Joshi, M, Carlini, AR, Murray, CK, Allen, LE, Huang, Y, Scharfstein, DO, O'Hara, NN, Gary, JL, Bosse, MJ, Castillo, RC, Bishop, JA, Weaver, MJ, Firoozabadi, R, Hsu, JR, Karunakar, MA, Seymour, RB, Sims, SH, Churchill, C, Brennan, ML, Gonzales, G, Reilly, RM, Zura, RD, Howes, CR, Mir, HR, Wagstrom, EA, Westberg, J, Gaski, GE, Kempton, LB, Natoli, RM, Sorkin, AT, Virkus, WW, Hill, LC, Hymes, RA, Holzman, M, Malekzadeh, AS, Schulman, JE, Ramsey, L, Cuff, JAN, Haaser, S, Osgood, GM, Shafiq, B, Laljani, V, Lee, OC, Krause, PC, Rowe, CJ, Hilliard, CL, Morandi, MM, Mullins, A, Achor, TS, Choo, AM, Munz, JW, Boutte, SJ, Vallier, HA, Breslin, MA, Frisch, HM, Kaufman, AM, Large, TM, Lecroy, CM, Riggsbee, C, Smith, CS, Crickard, CV, Phieffer, LS, Sheridan, E, Jones, CB, Sietsema, DL, Reid, JS, Ringenbach, K, Hayda, R, Evans, AR, Crisco, MJ, Rivera, JC, Osborn, PM, Kimmel, J, Stawicki, SP, Nwachuku, CO, Wojda, TR, Rehman, S, Donnelly, JM, Caroom, C, Jenkins, MD, Boulton, CL, Costales, TG, Lebrun, CT, Manson, TT, Mascarenhas, DC, Nascone, JW, Pollak, AN, Sciadini, MF, Slobogean, GP, Berger, PZ, Connelly, DW, Degani, Y, Howe, AL, Marinos, DP, Montalvo, RN, Reahl, GB, Schoonover, CD, Schroder, LK, Vang, S, Bergin, PF, Graves, ML, Russell, GV, Spitler, CA, Hydrick, JM, Teague, D, Ertl, W, Hickerson, LE, Moloney, GB, Weinlein, JC, Zelle, BA, Agarwal, A, Karia, RA, Sathy, AK, Au, B, Maroto, M, Sanders, D, Higgins, TF, Haller, JM, Rothberg, DL, Weiss, DB, Yarboro, SR, McVey, ED, Lester-Ballard, V, Goodspeed, D, Lang, GJ, Whiting, PS, Siy, AB, Obremskey, WT, Jahangir, AA, Attum, B, Burgos, EJ, Molina, CS, Rodriguez-Buitrago, A, Gajari, V, Trochez, KM, Halvorson, JJ, Miller, AN, Goodman, JB, Holden, MB, McAndrew, CM, Gardner, MJ, Ricci, WM, Spraggs-Hughes, A, Collins, SC, Taylor, TJ & Zadnik, M 2021, 'Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial', JAMA Surgery, vol. 156, no. 5. https://doi.org/10.1001/jamasurg.2020.7259

TY - JOUR

T1 - Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures

T2 - A Randomized Clinical Trial

AU - O'Toole, Robert V.

AU - Joshi, Manjari

AU - Carlini, Anthony R.

AU - Murray, Clinton K.

AU - Allen, Lauren E.

AU - Huang, Yanjie

AU - Scharfstein, Daniel O.

AU - O'Hara, Nathan N.

AU - Gary, Joshua L.

AU - Bosse, Michael J.

AU - Castillo, Renan C.

AU - Bishop, Julius A.

AU - Weaver, Michael J.

AU - Firoozabadi, Reza

AU - Hsu, Joseph R.

AU - Karunakar, Madhav A.

AU - Seymour, Rachel B.

AU - Sims, Stephen H.

AU - Churchill, Christine

AU - Brennan, Michael L.

AU - Gonzales, Gabriela

AU - Reilly, Rachel M.

AU - Zura, Robert D.

AU - Howes, Cameron R.

AU - Mir, Hassan R.

AU - Wagstrom, Emily A.

AU - Westberg, Jerald

AU - Gaski, Greg E.

AU - Kempton, Laurence B.

AU - Natoli, Roman M.

AU - Sorkin, Anthony T.

AU - Virkus, Walter W.

AU - Hill, Lauren C.

AU - Hymes, Robert A.

AU - Holzman, Michael

AU - Malekzadeh, A. Stephen

AU - Schulman, Jeff E.

AU - Ramsey, Lolita

AU - Cuff, Jaslynn A.N.

AU - Haaser, Sharon

AU - Osgood, Greg M.

AU - Shafiq, Babar

AU - Laljani, Vaishali

AU - Lee, Olivia C.

AU - Krause, Peter C.

AU - Rowe, Cara J.

AU - Hilliard, Colette L.

AU - Morandi, Massimo Max

AU - Mullins, Angela

AU - Achor, Timothy S.

AU - Choo, Andrew M.

AU - Munz, John W.

AU - Boutte, Sterling J.

AU - Vallier, Heather A.

AU - Breslin, Mary A.

AU - Frisch, H. Michael

AU - Kaufman, Adam M.

AU - Large, Thomas M.

AU - Lecroy, C. Michael

AU - Riggsbee, Christina

AU - Smith, Christopher S.

AU - Crickard, Colin V.

AU - Phieffer, Laura S.

AU - Sheridan, Elizabeth

AU - Jones, Clifford B.

AU - Sietsema, Debra L.

AU - Reid, J. Spence

AU - Ringenbach, Kathy

AU - Hayda, Roman

AU - Evans, Andrew R.

AU - Crisco, M. J.

AU - Rivera, Jessica C.

AU - Osborn, Patrick M.

AU - Kimmel, Joseph

AU - Stawicki, Stanislaw P.

AU - Nwachuku, Chinenye O.

AU - Wojda, Thomas R.

AU - Rehman, Saqib

AU - Donnelly, Joanne M.

AU - Caroom, Cyrus

AU - Jenkins, Mark D.

AU - Boulton, Christina L.

AU - Costales, Timothy G.

AU - Lebrun, Christopher T.

AU - Manson, Theodore T.

AU - Mascarenhas, Daniel C.

AU - Nascone, Jason W.

AU - Pollak, Andrew N.

AU - Sciadini, Marcus F.

AU - Slobogean, Gerard P.

AU - Berger, Peter Z.

AU - Connelly, Daniel W.

AU - Degani, Yasmin

AU - Howe, Andrea L.

AU - Marinos, Dimitrius P.

AU - Montalvo, Ryan N.

AU - Reahl, G. Bradley

AU - Schoonover, Carrie D.

AU - Schroder, Lisa K.

AU - Vang, Sandy

AU - Bergin, Patrick F.

AU - Graves, Matt L.

AU - Russell, George V.

AU - Spitler, Clay A.

AU - Hydrick, Josie M.

AU - Teague, David

AU - Ertl, William

AU - Hickerson, Lindsay E.

AU - Moloney, Gele B.

AU - Weinlein, John C.

AU - Zelle, Boris A.

AU - Agarwal, Animesh

AU - Karia, Ravi A.

AU - Sathy, Ashoke K.

AU - Au, Brigham

AU - Maroto, Medardo

AU - Sanders, Drew

AU - Higgins, Thomas F.

AU - Haller, Justin M.

AU - Rothberg, David L.

AU - Weiss, David B.

AU - Yarboro, Seth R.

AU - McVey, Eric D.

AU - Lester-Ballard, Veronica

AU - Goodspeed, David

AU - Lang, Gerald J.

AU - Whiting, Paul S.

AU - Siy, Alexander B.

AU - Obremskey, William T.

AU - Jahangir, A. Alex

AU - Attum, Basem

AU - Burgos, Eduardo J.

AU - Molina, Cesar S.

AU - Rodriguez-Buitrago, Andres

AU - Gajari, Vamshi

AU - Trochez, Karen M.

AU - Halvorson, Jason J.

AU - Miller, Anna N.

AU - Goodman, James Brett

AU - Holden, Martha B.

AU - McAndrew, Christopher M.

AU - Gardner, Michael J.

AU - Ricci, William M.

AU - Spraggs-Hughes, Amanda

AU - Collins, Susan C.

AU - Taylor, Tara J.

AU - Zadnik, Mary

N1 - Funding Information: (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 Funding Information: Funding/Support: The study was funded by grant W81XWH-10-2-0134 from the DOD’s Congressionally Directed Medical Research Program (Drs O’Toole, Castillo, and Carlini). Publisher Copyright: © 2021 American Medical Association. All rights reserved.

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85103467918&partnerID=8YFLogxK

U2 - 10.1001/jamasurg.2020.7259

DO - 10.1001/jamasurg.2020.7259

M3 - Article

C2 - 33760010

AN - SCOPUS:85103467918

SN - 2168-6254

VL - 156

JO - JAMA Surgery

JF - JAMA Surgery

IS - 5

ER -

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

Abstract

Access to Document

Fingerprint

Cite this