UM School of Medicine Researchers Found No Benefit to Adding Tobramycin to Vancomycin and Potential Harms for Open Fractures

A large multicenter clinical trial found no benefit to using two antibiotic powders — vancomycin, which targets gram-positive bacteria seen commonly in surgical infections, and tobramycin, which targets gram-negative bacteria that can also cause infection after fracture — during surgery for high‑risk leg fractures involving the shin bone.

The study, led by orthopedic surgeons and researchers at the University of Maryland School of Medicine and the Major Extremity Research Consortium (METRC) at the Johns Hopkins Bloomberg School of Public Health, showed that applying both antibiotics directly into the surgical wound did not reduce deep surgical site infections compared with using vancomycin powder alone.

The trial involved more than 1,500 patients from 39 U.S. trauma centers, including the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, and was published today in the Journal of the American Medical Association.

In the study, surgical patients with periarticular tibial fractures were randomly assigned to have their surgical incision treated with tobramycin powder plus vancomycin powder or vancomycin powder alone. Within six months of surgery, deep surgical site infections occurred in 7.4% of patients who received tobramycin plus vancomycin compared to 6.6% who received vancomycin alone. The research team also observed no advantage of the combination to prevent gram‑negative bacterial infections, which are resistant to vancomycin.

“We specifically tested the common belief that adding an aminoglycoside like tobramycin would cut down gram‑negative infections,” said principal investigator Robert O’Toole, MD, Professor of Orthopedics at UMSOM and Chief of Orthopaedics at the R Adams Cowley Shock Trauma Center. “That simply didn’t bear out. Vancomycin alone remains a solid option for reducing gram‑positive infections, but our data do not support routinely adding tobramycin powder.”

Intrawound tobramycin powder has become more commonly used by orthopaedic surgeons over the past decade to reduce infections in patients undergoing surgery for a fracture. The trial demonstrated that tobramycin powder plus vancomycin powder did not reduce the risk of infection compared to vancomycin powder alone. In a subgroup of patients with severe fractures where the bone broke through the skin (open fractures), the risk of infection was higher in those receiving tobramycin powder plus vancomycin powder compared to vancomycin alone. The researchers said the subgroup results should be interpreted cautiously due to smaller group of patients with open fractures.

“The findings should change surgeons' practice to avoid the use of intrawound tobramycin powder in this population, as there is no evidence that it prevents infections and might be harmful in open fracture patients,” said study co-author Nathan O’Hara, PhD, MHA, Associate Professor of Orthopedics at UMSOM. “Surgeons should not expect benefit from this combination approach in routine practice.”

Added study co-author Gregory Schrank, MD, MPH, Assistant Professor of Medicine at UMSOM: “Vancomycin alone remains an effective option for reducing gram‑positive infections, but our data do not support routinely adding tobramycin powder.”

Adverse events, including kidney issues and allergic reactions, were similar in both groups, with very low rates observed.

“Serious infections after tibial plateau and pilon fracture surgery can lead to repeat operations, prolonged antibiotics, delayed healing, and long‑term disability, so infection control remains tantamount,” said UMSOM Dean Mark Gladwin, MD. “This well-designed study, drawing from diverse trauma centers nationwide with its high protocol adherence and follow-up, provides practical guidance for infection prevention protocols in orthopaedic trauma.”

Researchers and orthopedic surgeons from the following institutions participated in this study: R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Johns Hopkins Bloomberg School of Public Health, University of Southern California Keck School of Medicine, Vanderbilt University Medical Center, University of Kentucky, University of Oklahoma, 7Indiana University Health Methodist Hospital, Dartmouth-Hitchcock, Brigham and Women’s Hospital at Harvard Medical School, Walter Reed National Military Medical Center, Loyola University Medical Center.

“The study results were surprising but serve as a perfect illustration of why there is no substitute for doing these multicenter, randomized clinical trials,” said Renan Castillo, PhD, Professor of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health, who served as the study methods center principal investigator.

The study was supported by the U.S. Department of Defense (award W81XWH‑19‑1‑0848).