Infective endocarditis meets native vertebral osteomyelitis: a mortality perspective

Background: Native vertebral osteomyelitis and infective endocarditis (NVO $+$ IE) are increasingly recognized as overlapping entities, sharing common risk factors (e.g., advanced age, immunosuppression) and similar pathogen profiles, most commonly Staphylococcus aureus and streptococci. Concurrent infection presents unique diagnostic and therapeutic challenges, leading to uncertainty regarding clinical outcomes and mortality. Therefore, we aimed to systematically evaluate the combined mortality associated with concomitant NVO $+$ IE and to summarize the available clinical characteristics from published studies. Methods: A systematic review was conducted following the PRISMA framework. The databases searched included MEDLINE, Embase, Cochrane Library, and Scopus from 1970 to October 2023. Studies were included if they involved at least 10 adult patients diagnosed with NVO and IE and provided mortality data. Two reviewers independently screened the references, extracted the data, and evaluated the methodological quality using a dedicated tool. A random-effects meta-analysis was performed to aggregate in-hospital, 1-month, 1-year, and 3-year mortality rates. Results: A total of 16 studies (12 retrospective, 3 prospective, 1 mixed) were included, involving 641 patients (mean age 67.1 years) with NVO $+$ IE. In-hospital mortality was 14.0 % (95 % CI: 10.0 %-20.0 %). At 1 month, mortality was 9.0 % (95 % CI: 5.0 %-17.0 %), rising to 18.0 % (95 % CI: 13.0 %-24.0 %) by 1 year and 16.0 % (95 % CI: 3.0 %-50.0 %) by 3 years. Significant between-study heterogeneity was observed ( $I^2$  range: 3 %-70 %). Common co-morbidities included diabetes mellitus (23.7 %), chronic renal failure (15.0 %), and immunosuppression (15.0 %). Streptococci (31.5 %), S. aureus (25.2 %), and enterococci (17.7 %) were the primary pathogens. Cardiac valve surgery and spinal surgery were reported in 47.5 % and 29.9 % of patients, respectively. A subgroup analysis on 1-month mortality showed that S. aureus predominance was associated with a significantly higher mortality compared to streptococci. Certainty in the estimates was low due to imprecision and methodological limitations. Conclusions: Concomitant NVO $+$ IE is associated with substantial mortality, especially for S. aureus, underscoring the need for earlier diagnosis, coordinated multidisciplinary management, and standardized treatment protocols. Future prospective, high-quality studies are needed to clarify optimal strategies for diagnostic workup and surgical intervention for this complex clinical scenario.