The Impact of Location on De Novo Spondylodiscitis: Regions Matter but Are Secondary to Comorbidities

<b>Background/Objectives</b>: Primary spondylodiscitis (SD) cases surging in incidence globally remain a diagnostic and therapeutic challenge for physicians. The effect of lesion location on outcomes remains unclear. This study aims to assess the 90-day all-cause readmission rate in patients suffering from spondylodiscitis in different regions of the spine, with a secondary objective of comparing in-hospital mortality rates. <b>Methods</b>: Utilizing the 2020 Nationwide Readmissions Database (NRD), USA, adult patients (>18 years) were selected by diagnosis with ICD-10 codes for primary spondylodiscitis. Patients were categorized by localization into eight groups, excluding multifocal patients. Comparative analysis and logistic regressions were performed. <b>Results</b>: Among 5547 patients, lumbar SD was most prevalent, followed by thoracic and lumbo-sacral regions. Cervical SD had the lowest readmission rate (31.3%) and lower odds versus lumbar SD (adjusted OR = 0.73; <i>p</i> = 0.007). Other regions showed no significant differences. In-hospital mortality varied by location. The sacral region, renal failure, and advanced age were the strongest mortality predictors. <b>Conclusions</b>: While the incidence of spondylodiscitis varies by location on the spine, we found no significant differences in readmission rates across regions. However, there were substantial differences in in-hospital mortality rates. Comorbidities, particularly renal failure and advanced age, appear to outweigh spinal localization as risk factors for mortality and readmission.