Study ‘Challenges’ Standard of Prolonged Antibiotics for Orthopedic Infections

Giving no more than a week’s worth of systemic antibiotics was as effective as a standard multi-week course for preventing treatment failure in patients who underwent surgery for orthopedic infection paired with implant of a local antibiotic carrier, an open-label noninferiority trial showed.

Among 475 patients included in the primary analysis, definite treatment failure at 12 months occurred in 11.1% of those randomized to 7 or fewer days of postoperative systemic antibiotics versus 14.1% of those who received 4 or more weeks of treatment, with that difference meeting the trial’s noninferiority margin of 10 percentage points.

At a 6-week follow-up visit, 17.2% of those in the short-duration antibiotic group and 45.2% of those in the long-duration antibiotic group reported symptoms that were potentially linked to antibiotic treatment, reported Martin McNally, MD, of Oxford University Hospitals in England, and colleagues in the New England Journal of Medicine.

“This trial challenges the standard of care for orthopedic infection,” the authors wrote. “Treatment with local antibiotics delivered by a carrier implanted during surgery allows patients and clinicians to consider a shorter duration of systemic antibiotic regimen after surgery.”

Although the results appear to support that combination approach, McNally and team cautioned that “a substantial amount of high-quality data is needed before local therapy is adopted as the primary approach in clinical practice.”

The management of bone and joint infections usually includes a combination of surgical debridement and extended administration of systemic antibiotic therapy. Local antibiotics delivered by an implanted licensed carrier are increasingly being used along with systemic antibiotics in the treatment of orthopedic infections.

“Theoretical advantages of local antibiotics include delivery of very high antibiotic concentrations locally, limited systemic absorption of antibiotics and potentially fewer side effects, and improved antimicrobial stewardship,” the authors noted. “However, local therapy may be associated with an increased risk of hypercalcemia, renal impairment, or local problems with wound leakage or fracture of an antibiotic-loaded spacer.”

The Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO) trial included adults who were undergoing curative surgery for an orthopedic infection. All patients had a licensed local-antibiotic carrier implanted during surgery and received broad-spectrum antibiotic systemic therapy perioperatively.

The trial didn’t include patients who had antibiotic powder sprinkled into operative sites, those with irrigation devices, or patients who received intraosseous infusions. Their exclusion means the SOLARIO results “should not be used to support the use of these techniques for delivery of local antibiotics,” McNally and team cautioned.

The 25-site trial ran from February 2019 through August 2023. The choice of local and systemic antibiotics was made by infectious disease specialists at the individual trial sites. The study’s primary endpoint, definite treatment failure within 12 months of surgery, was defined as a surgical-site sinus tract or purulence, infection, newly elevated biomarkers during aspiration or reoperation, or death from infection at the original surgical site.

Median ages at surgery in the short- and long-duration groups were 57 and 59 years, respectively, and 28.7% and 29.4% of patients were women. The median Charlson Comorbidity Index score in both groups was 2. The most frequent surgery indication in both groups was debridement for osteomyelitis or fracture-related infection, in 35.6% and 34.9%, respectively, and Staphylococcus aureus was the most frequent infecting organism (33.9% and 35.3%).

The median duration of systemic antibiotic therapy was 6 days among the short-duration patients and 42 days in the long-duration group.

Patients in the short-duration group stayed a mean 11.9 days in the hospital compared with 14.8 days for those in the long-duration group. Serious adverse events occurred in 17.1% and 19.9%, respectively. Overall survival rates at 12 months were 97.9% among the short-duration patients and 96.3% among the long-duration patients.

SOLARIO’s clinical results could also have financial effects. “Direct costs will likely be lower with the short duration than with the long duration,” McNally and colleagues noted, “given that the short-duration group used fewer systemic antibiotics and had a shorter length of hospital stay and lower number of events with an indication for treatment.”

Study limitations included the trial’s open-label design, as well as the potential for selection bias, since clinicians may not have recruited patients with a high risk of treatment failure. The trial also wasn’t designed to evaluate specific local antibiotics.