Martin McNally, Maria Dudareva, Michelle Kümin, Werner Vach, Claire L Scarborough, Matthew J Cichero, Ricardo Sousa, Jamie Ferguson, David A Stubbs, Bridget L Atkins, Alex J Ramsden, Bernadette C Young, Andre D Carvalho, Adrian R Kendal, Abtin Alvand, Antony J R Palmer, Con L Loizou, Ben Kendrick, Adrian H Taylor, Amirul Islam, Michael J Riste, Anand Pillai, Sunil K Sharma, Jonathan Folb, Neal Jacobs, Simon C Ellis, Aaron B Y Ng, Daniel Perez-Prieto, Irene K Sigmund, Reinhard Windhager, Alexis D Iliadis, Andrew J F Bing, Henry Wynn Jones, John Williams, Ben J Ollivere, Volker Alt, Simon Warren, Neil E Jenkins, Andreas Leithner, Harriet C Hughes, Steve A Jones, O Martin Williams, Matthew Scarborough
Among patients who had undergone orthopedic surgery and received local antibiotics, a short course of systemic antibiotics was noninferior to a long course with respect to definite treatment failure by 12 months. (Funded by the European Bone and Joint Infection Society and others; SOLARIO ClinicalTrials.gov number, NCT03806166.).
BACKGROUND: Orthopedic infection is usually managed with surgery and prolonged systemic antibiotic therapy. Whether local antibiotics delivered by a product implanted at the infection site during surgery can reduce the duration of systemic antibiotic therapy is unclear.
METHODS: In a multicenter, open-label, noninferiority trial, we randomly assigned, in a 1:1 ratio, adults who had undergone surgery for orthopedic infection and implantation of a local-antibiotic carrier to receive postoperative systemic antibiotic therapy for a long (≥4 weeks) or short (≤7 days) duration. The primary outcome was definite treatment failure by 12 months, assessed according to protocol-defined criteria by a clinical end-point committee whose members were unaware of the trial-group assignments. The noninferiority margin was 10 percentage points.
RESULTS: A total of 500 patients underwent randomization, of whom 475 were assessed in the primary analysis. Definite treatment failure occurred in 34 of 241 patients (14.1%) in the long-duration group and in 26 of 234 patients (11.1%) in the short-duration group (risk difference [negative values favor the short duration], -3.0 percentage points; 95% confidence interval [CI], -9.0 to 3.0), which met the prespecified noninferiority margin. In sensitivity analyses in the included population (497 patients) and the per-protocol population (457 patients), results were consistent with those of the primary analysis (risk difference, -2.4 percentage points [95% CI, -8.2 to 3.5] and -2.7 percentage points [95% CI, -8.8 to 3.4], respectively). By week 6 after surgery, symptoms potentially related to treatment had occurred in 45.2% of the patients in the long-duration group and in 17.2% of those in the short-duration group (risk difference, -28.0 percentage points; 95% CI, -36.4 to -19.6).
CONCLUSIONS: Among patients who had undergone orthopedic surgery and received local antibiotics, a short course of systemic antibiotics was noninferior to a long course with respect to definite treatment failure by 12 months. (Funded by the European Bone and Joint Infection Society and others; SOLARIO ClinicalTrials.gov number, NCT03806166.).