International Reference Pricing Across Medicare and Medicaid: Evaluating CMS Models

# International Reference Pricing Across Medicare and Medicaid: Evaluating CMS Models *Published: 2026 May 12* Intrawound Tobramycin Plus Vancomycin to Prevent Surgical Site Infection in Tibial Fractures: The TOBRA Randomized Clinical Trial. Major Extremity Trauma Research Consortium (METRC); O'Toole RV(1), O'Hara NN(1), Carlini AR(2), Schrank GM(1), Chung S(2), Gary JL(3), Obremskey W(4), Matuszewski PE(5), Teague D(6), Natoli RM(7), Gitajn IL(8), Weaver MJ(9), Renninger CH(10), Levack AE(11), Degani Y(1), Collins SC(2), Weston-Farber E(2), Howe AL(1), Thompson RE(2), Castillo RC(2), Karunakar MA(12), Blum L(12), Harmer L(12), Hsu JR(12), Kempton LB(12), Phelps KD(12), Seymour RB(12), Sims SH(12), Acharya MS(12), Callahan H(12), Chavez-Araujo LM(12), Churchill C(12), Gambuzza MP(12), Haim KR(12), Ishman E(12), Kendall JS(12)(13), Mullis ND(12), Young C(12), Pilson HT(14), Carroll EA(14), Goodman JB(14), Holden MB(14), Jones AL(15), Moon C(16), Lin CA(16), Marecek GS(16), Moffitt GB(17), Conlan T(17), George AV(17), Fisher LA(8), Mullin DS(8), Recendez CL(8), Aneja A(18), Brameier DT(18), Heng M(18)(19), Ly TV(18), Stenquist DS(18), Suneja N(18), Wignakumar T(18), Borgida JS(18), Policicchio TJ(18), Hanson GR(20), Alese OM(20), Ricci WM(21), Behrens SB(21), Dvorzhinskiy A(21), Bilodeau RE(21), Klinger CE(21), Mullis BH(7), Jang Y(7), Lopas LA(7), McKinley TO(7), O'Neill DC(7), Szatkowski JP(7), Virkus WW(7), Hill LC(7), Gaski G(22), Hymes RA(22), Ahn J(22), Goch AM(22), Holzman M(22), Malekzadeh AS(22), Schulman JE(22), Rivera JC(23), Krause PC(23), Bridgman C(23), Cohen J(11), Eikani C(11), Chavez M(11), Kudulis M(11), Warner SJ(24), Achor TS(24), Choo A(24), Eastman JG(24), Kellam PJ(24), Boutte SJ(24), Guevara KD(24), Reid KR(25), Vallier HA(26), Tucci AV(26), Davis JM(27), Bell AC(1), Bonyun ME(1), Healey K(1), Li V(1)(28), McKibben NS(1)(29), Nascone J(1), Okhuereigbe D(1), Sciadini MF(1), Slobogean G(1)(30), Zingas N(1), Kovvur M(1)(31), Lawrence JE(1)(32), Phipps H(1), Rudnicki J(1)(33), Turner KE(1)(34), Hayda R(35), Evans AR(35), Quinnan S(36), Benitez A(36), Rehman S(37), Soderquist MC(37)(38), Townsend CB(37), Caroom C(39), Collins AC(40), Okwumabua E(40), Shaikh HS(40), Spitler CA(41), Agarwal A(41), Johnson MD(41), Haller JM(42), Marchand LS(42), Alfonso NA(43), Gorman MA(43), Charlton WM(5), Scott BR(5), Kraus KM(5), Meredith SJ(44), Talwar S(44), Bergin PF(45), Jha AJ(45)(46), McGee S(45), Nehete PV(45), Pryor TA(45), Spears I(45), Chen AT(47), Kelley B(47), Nez NR(47), Ertl WJ(6), Hull BR(6), Blumenthal S(3), Patterson JT(3), Flynn C(3), Ross RC(3), Agarwal A(48), Weiss DB(49), Hadeed MM(49), Yarboro SR(49), Daoud T(49), McVey ED(49), Whiting PS(50), Domes C(50), Goodspeed DC(50), Kuhn GR(50), Boyce R(4), Libos A(4)(51), Mitchell PM(4), Moreno-Diaz AF(4), Ponce RB(4)(52), Stinner DJ(4), Tatman LM(4), Velasco-Castro J(4), Trochez K(4), Satpathy J(53), Zuelzer DA(53), Potter BK(10)(54). Author information: (1)R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore. (2)Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. (3)University of Southern California Keck School of Medicine, Los Angeles. (4)Vanderbilt University Medical Center, Nashville, Tennessee. (5)University of Kentucky, Lexington. (6)University of Oklahoma Medical Center, Oklahoma City. (7)Indiana University Health Methodist Hospital, Indianapolis. (8)Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. (9)Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. (10)Walter Reed National Military Medical Center, Bethesda, Maryland. (11)Loyola University Medical Center, Maywood, Illinois. (12)Atrium Health-Carolinas Medical Center, Charlotte, North Carolina. (13)Now with Loma Linda School of Medicine, Loma Linda, California. (14)Atrium Health-Wake Forest Baptist, Winston-Salem, North Carolina. (15)Baylor Scott & White Health, Dallas, Texas. (16)Cedars-Sinai Medical Center, Los Angeles, California. (17)Corewell Health, Grand Rapids, Michigan. (18)Harvard University, Boston, Massachusetts. (19)Now with Boston Medical Center-Brighton. (20)Hennepin Healthcare, Minneapolis, Minnesota. (21)Hospital of Special Surgery & NewYork-Presbyterian Hospital, New York. (22)Inova Fairfax Medical Campus, Fairfax, Virginia. (23)Louisiana State University, New Orleans. (24)McGovern Medical School at the University of Texas Health Science Center at Houston. (25)Medical University of South Carolina, Charleston. (26)MetroHealth Medical Center, Cleveland, Ohio. (27)Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania. (28)Now with University of Texas Southwestern, Dallas. (29)Now with Oregon Health & Science University, Portland. (30)Now with University of California, Irvine. (31)Now with University of Pittsburgh, Pennsylvania. (32)Now with MedStar Health, Washington, DC. (33)Now with Johns Hopkins Hospital, Baltimore, Maryland. (34)Now with Georgetown University, Washington, DC. (35)Rhode Island Hospital at Brown University, Providence. (36)St Mary's Medical Center, West Palm Beach, Florida. (37)Temple University Hospital, Philadelphia, Pennsylvania. (38)Now with Robert Wood Johnson Barnabas Health, Jersey City, New Jersey. (39)Texas Tech University Health Sciences Center, Lubbock. (40)Ohio State University Medical Center, Columbus. (41)University of Alabama at Birmingham. (42)University of Utah, Salt Lake City. (43)University of Colorado Medicine, Aurora. (44)University of Maryland Capital Region Health, Largo. (45)University of Mississippi Medical Center, Jackson. (46)Now with Maimonides Medical Center, Brooklyn, New York. (47)University of North Carolina School of Medicine, Chapel Hill. (48)University of Texas Health Sciences Center, San Antonio. (49)University of Virginia Medical Center, Charlottesville. (50)University of Wisconsin, Madison. (51)Now with Fundacion Santa Fe de Bogota, Colombia. (52)Now with Wright State University Boonshoft School of Medicine, Dayton, Ohio. (53)Virginia Commonwealth University, Richmond. (54)Now with the University of Pennsylvania, Philadelphia. Comment in doi: 10.1001/jama.2026.4070. doi: 10.1001/jama.2022.24075. doi: 10.1001/jamanetworkopen.2025.59349. ## IMPORTANCE Previous research has suggested that intrawound vancomycin powder reduces deep surgical site infections among patients with periarticular tibial fractures at high risk of infection. It is unknown whether the addition of tobramycin powder further decreases infection rates. ## OBJECTIVE To compare whether the combination of tobramycin plus vancomycin vs vancomycin alone delivered as intrawound powder at the time of definitive fixation reduces deep surgical site infections. DESIGN, SETTING, AND PARTICIPANTS Open-label, assessor-masked, randomized clinical trial conducted at 39 US trauma centers. Eligible patients were adults with an operatively treated periarticular tibial fracture (either tibial plateau or pilon) who met 1 of 3 criteria for elevated infection risk. Enrollment occurred between June 18, 2021, and December 12, 2024 (final follow-up, July 15, 2025). ## INTERVENTIONS Intrawound tobramycin (1.2 g) plus vancomycin (1.0 g) powder vs intrawound vancomycin (1.0 g) powder delivered at the time of definitive fixation. MAIN OUTCOMES AND MEASURES The primary outcome was a deep surgical site infection requiring surgical management within 182 days of definitive fracture fixation. Secondary outcomes included deep surgical site infections with pathogens that were gram-negative only, deep surgical site infections with at least 1 pathogen that was gram-positive, deep surgical site infections with polymicrobial cultures, deep surgical site infections with negative culture results, and cellulitis or skin infections treated only with antibiotics. ## RESULTS Among the 1660 participants randomized, 1528 (mean age, 47.0 [SD, 14.3] years; 603 female [39.5%]; 925 male [60.5%]) were included in the primary analysis. Deep surgical site infections occurred in 51 of 753 participants (182-day probability, 7.4%) in the tobramycin plus vancomycin group and 47 of 775 participants (182-day probability, 6.6%) in the vancomycin alone group (hazard ratio, 1.11; 95% bayesian credible interval, 0.75-1.66; posterior probability of superiority, 29.7%). The threshold required for superiority was not reached for any secondary outcome. CONCLUSIONS AND RELEVANCE Among patients with operatively treated periarticular tibial fractures at high risk of infection, adding intrawound tobramycin powder to vancomycin powder at the time of definitive fixation did not reduce deep surgical site infections compared with vancomycin powder alone. ## TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02227446. DOI: 10.1001/jama.2026.4023 PMCID: PMC13084553 DOI: 10.1001/jama.2026.3536