Protocol of a short post-surgical antibiotic therapy in spine infections - prospective, randomized, unblinded, non-inferiority trials(SASI trials)

Abstract

Background There are several open scientific questions regarding the optimal antibiotic treatment of spine infections (SI) with or without an implant. The duration of post-surgical antibiotic therapy is debated.Methods We will perform and perform two unblinded randomized -controlled RCTs. We hypothesize that shorter durations of systemic antibiotic therapy after surgery for SI are non-inferior (10% margin, 80% power, ɑlpha 5%) to existing (long) treatment durations. The RCTs allocate the participants in two arms of 2 x 59 episodes each: 3 vs. 6 weeks of targeted post-surgical systemic antibiotic therapy for implant-free spine infections (two positive microbiological samples); or 6 vs. 12 weeks for implant-related spine infections. This equals a total of 236 adult SI episodes (randomization schemes 1:1) with a minimal follow-up of 12 months. All participants have a concomitant multidisciplinary surgical, re-educational, internist and infectious diseases care. We perform three interim analyses that are evaluated, in a blinded analysis, by an independent Study Data Monitoring Committee. Besides the primary outcome remission, we also assess adverse events of antibiotic therapy, changes of the patient’s nutritional status, the influence of immune suppression, total costs, functional scores, and the timely evolution of the (surgical) wounds. We define infection as the presence of local signs of inflammation (pus, wound discharge, calor, rubor) together with microbiological evidence of the same pathogen(s) in at least two intraoperative samples; and remission as absence of clinical, laboratory and/or radiological evidence of (former or new) infection.Discussion Provided that there is adequate surgical debridement, both RCTs enable to potentially prescribe less antibiotics during the therapy of SI; with potentially less adverse events and reduced overall costs.