In the last decades, knowledge on the clinical course, diagnosis and treatment of infective endocarditis has substantially increased. Despite these developments, data on the association between infective endocarditis and spondylodiscitis in non-referred patients are still lacking. The presence of spondylodiscitis (18%) in this all-comer registry shows an increased inflammation burden at and during admission. The observed difference in normalisation of CRP levels is particularly apparent in the final phase of antibiotic treatment but not related to infectious complications. Knowledge of this delayed normalisation of the inflammation burden is important in considering the need for additional imaging in such patients.

In the present series, spondylodiscitis occurred in 18% of the patients and was primarily accompanied by back pain at presentation. Its presence was not related to the observed ratio of distal organ embolisation. Earlier we reported a distant embolisation rate in non-referred patients of 24% [14].

Unfortunately, the ESC-ENDO Registry [21, 22] did not register spondylodiscitis; however, their overall PET-CT experience showed a spinal uptake in 21.8% of patients who underwent a PET scan. It is of note that the use of PET-CT is very variable in the registry (mean 16.6% range 2.1–33.9%) and in the literature, which may be an important caveat in determining the prevalence of spondylodiscitis.

Urgent surgery for endocarditis during hospitalisation was infrequent and not associated with spondylodiscitis. When needed, surgery in spondylodiscitis patients was performed later than in non-spondylodiscitis patients (36 ± 9 days vs 15 ± 12 days; p = 0.007). Mortality and the relapse rate of infective endocarditis at 6 months was not different when spondylodiscitis was present.

CRP is an acute-phase reactant protein that is produced by the liver in response to inflammation. It is commonly used as a marker of inflammation and can help monitor disease activity, assess response to treatment and predict prognosis in various inflammatory conditions. Our admission CRP and leucocytes levels were comparable if not higher than those found in the ESC-ENDO Registry [21, 22] which does not report follow-up CRP measurements. Heiro et al. [23] report a significant trend between the level of CRP at admission and both short-term and 1‑year outcome. In the trend analysis of association, it was found that a CRP increment of 50 mg/l at admission was associated with a 1.33-fold hazard for in-hospital death (HR 1.33, 95% CI 1.06 to 1.68; p = 0.015) Among their surgically treated patients, the hazard for in-hospital death for the patients with CRP values ≥ 100 mg/l at admission was 6.85-fold as compared with those with CRP values < 100 mg/l at admission (HR 6.85, 95% CI 1.51 to 30.95; p = 0.013).

Serial CRP measurements are valuable in infective endocarditis as they allow us to monitor disease activity over time. Changes in CRP levels and leucocyte levels can reflect fluctuations in the inflammatory process, providing insights into the effectiveness of treatment or disease progression [24]. Guideline-driven antibiotic therapy indeed shows a gradual normalisation of these levels in uncomplicated cases. However, spondylodiscitis influences the CRP levels both at admission and during the treatment period with slower normalisation. The second consequence of spondylodiscitis is the duration of intravenous treatment: always 6 weeks irrespective of the micro-organism. The clinical follow-up thereafter is similar for patients with and without spondylodiscitis and finally, we did not observe more relapses in the two groups.

In contrast to previous retrospective studies with smaller sample sizes, the current study reports a significantly higher admission level of CRP and lower level of haemoglobin in patients with concomitant spondylodiscitis when compared with patients with infective endocarditis alone [14, 26]. Additionally, the inflammation burden (denoted as CRP area under the curve) during the course of the disease is larger in spondylodiscitis patients. This indicates that patients with concomitant spondylodiscitis are going through a more severe systemic infection, also given their higher leucocyte levels.

Tracking the inflammation burden in infective endocarditis can provide valuable information about disease activity, treatment effect and prognosis. Elevated and persistent CRP levels with or without fever may reflect ongoing disease activity, and renewed CRP elevation in the later phase may reflect new inflammatory activity, more likely other than endocarditis. Our study demonstrates the value of monitoring the CRP area under the curve when spondylodiscitis itself shows a prolonged period of elevated CRP levels without endocarditis complications. Recognition of this different pattern of CRP normalisation in both the initial and later clinical phase may guide physicians in their awareness that when the clinical condition remains stable, it is not necessary to perform immediate new cardiac imaging for suspicion of infectious valve complications.

Fortunately, the increased inflammation burden does not interfere with the duration of hospital stay, the rates of cardiac surgery and mortality. It seems that once targeted therapy is started, the spondylodiscitis can be treated equally effectively, albeit slower.

Interestingly, we report a trend towards Enterococcus-mediated spondylodiscitis in our unselected population. Enterococci are the third most common species to cause infective endocarditis [24, 25] and have a large impact on patients due to the development of a protective bacterial film [11, 12] leading to increased inflammation burden in endocarditis patients. They are more frequently found in elderly patients and particularly in the hospital environment mostly due to urinary and bowel interventions. Finally, they have intrinsic resistance to some antibiotics [26, 27].

There are several limitations that need to be taken into account. The main limitation of this study is its single-centre nature, which resulted in a relatively small group of patients with infective endocarditis. Also, 16 patients without valve abnormalities are reported because they were clinically treated as having endocarditis (Table S1, S2 of the Electronic Supplementary Material). Secondly, it is important to mention that the duration of hospitalisation for patients receiving ambulatory treatment was calculated from the day of admission until the end of the outpatient antibiotic treatment. Thirdly, not all patients underwent CT imaging, which could lead to spondylodiscitis being undetected.

Lastly, the inflammation burden expressed as the area under the CRP curve was calculated from time intervals which were determined in daily practice.