Conservative Versus Surgical Treatment of Native Vertebral Osteomyelitis: a Randomized Multicentre Trial

INTRODUCTION AND EVIDENCE. Native vertebral osteomyelitis (NVO) is mainly caused by hematogenous spread from a distant infection focus (e.g. respiratory, urogenital, intestinal tract, oral cavity, skin or intravascular device), typically involving the intervertebral disc space and adjacent vertebral bodies ("spondylodiscitis"). Rarely NVO develops after percutaneous injection or intervention in the spine region without hardware implantation. Recalcitrant back pain unresponsive to conservative measures along with increased systemic inflammatory biomarkers (C-reactive protein) and/or fever or chills is the initial manifestation prompting additional investigations such as collecting blood cultures and spine imaging. Nevertheless, NVO is often diagnosed late or the diagnose is missed, which has a high impact on patient morbidity and mortality, life quality and healthcare costs (prolonged hospital stay, surgical intervention, antimicrobial therapy). Unrecognized primary infection focus causing NVO may lead to further hematogenous spread, potentially affecting other organs, joints and heart valves. The annual incidence of NVO is reported at 5.78 per 100.000 per year and is increasing in the past decades due to aging population, rise of immunocompromised patients and more invasive treatments. The incidence also increased, in part, due to improvements in diagnostic possibilities, including imaging and non-culture-based microbiological techniques. The mortality of NVO ranges between 5 and 20 %, depending on the primary infectious focus, causing pathogen and patient comorbidities.

The treatment goal of NVO is pain relief, prevention or reversion of neurologic deficits, eradication of infection, and establish spinal stability. The indication for conservative versus surgical treatment of uncomplicated NVO (no relevant abscesses, no neurologic impairment, no spine instability) are not uniform and largely depend on institutional/ regional /national preferences, traditions or random choice. A recent systematic review identified only three studies that comparing conservative to surgical treatment. All three studies are retrospective in design. The indication for surgical treatment in the first two studies was neurologic impairment, extensive bone destruction, epidural abscess formation, and failure of non-operative treatment or intractable back pain. These studies reported the complications and reoperation rates, but no formal statistical analysis was performed, in particular the long-term outcome of both treatment modalities is lacking. Other authors (Nastro et al.) treated with orthesis or spinal instrumentation and found no significant differences in both groups after 9 months. No study so far used uniform definition and stratification criteria for infection, neither used a standardized antimicrobial therapy, allowing to evaluate the outcome on the pathogen, pathogenesis, or primary focus of infection. Therefore, evidence-based data is missing to develop rational treatment guidelines for optimal treatment of NVO.

We hypothesize that the conservative treatment of uncomplicated NVO is non-inferior to surgical therapy regarding infection outcome.

AIM. The aim of this multicenter, randomized, controlled study is to compare the long-term outcome including the proportion of infection-free subjects, functional outcome and socioeconomic outcome between conservative and surgical treatment approaches providing novel high-class evidence to resolve this unknown.

MATERIAL AND METHODS. A total of 350 subjects from 8 different centers (Berlin, Munich, Dresden, Leipzig, Jena, Bonn, Magdeburg, Aachen, Cologne, Hamburg) will be screened. With 8 participating study sites, 200 patients are expected to be randomized per year. With a recruitment period of two years (i.e. 400 patients) and a dropout rate of 15%, 140 patients could be analyzed regarding the primary endpoint at 12 months.