Article Reviewed Takahashi T, Inose H, Hirai T, Matsukura Y, Morishita S, Egawa S, Hashimoto J, Takahashi K, Yoshii T. Factors associated with the time required for CRP normalization in pyogenic spondylitis: A retrospective observational study. North American Spine Society Journal (NASSJ). 2024;17doi:10.1016/j.xnsj.2023.100301

https://www.nassopenaccess.org/article/S2666-5484(23)00103-8/fulltext Commentary Pyogenic spondylitis is a challenging clinical entity for which management and following are important. The currently reviewed study by Takahashi et al evaluated factors associated with a prolonged time to normalization of C-reactive protein (CRP) in a retrospective, single-institution, observational cohort study. The premise of the current study was that CRP normalization was an indicator for infection control. The reviewed paper establishes the role of CRP as such. This marker is an acute phase reactant that is produced by hepatocytes in response to inflammation. CRP levels are preferred over other inflammatory markers such as erythrocyte sedimentation rate (ESR) because they are more sensitive to changes in the infection status. As mentioned by the authors, the 2015 Infectious Diseases Society of America Clinical Practice Guidelines recommend using CRP levels to assess the treatment response in pyogenic spondylitis making it a suitable choice for the currently reviewed study. The reviewed study focused on patients with spontaneous pyogenic spondylitis (not including postoperative infections). Consecutive patients between May 2010 and August 2021 were included for a total cohort of 108 patients. Among these, there was a mix of cases that were managed conservatively and operatively. The type of management likely impacts the time to CRP normalization, but the authors analyzed all cases together to avoid biasing the selection based on the severity of the case. A number of patient and radiographic parameters were gathered for those identified for the study. The number of days from the first visit to CRP normalization (defined as CRP <= 0.14 mg/dL) was then evaluated for each patient in the cohort. For the cases where CRP did not normalize, the number of days until the date of final blood sampling was evaluated. CRP normalization was observed in 83 patients (77%) and the mean time for normalization was 146 days. Of the 25 patients for whom CRP normalization was not observed, 17 were transferred to other hospitals and 1 died. Three patients continued to be followed for >400 days without normalization. It is possible that those infections took an especially long time to control, but it would be interesting to understand more of the clinical picture for these cases. Additional interventions may have been needed to fully control those infections. It was found that higher neutrophil percentage, lymphocyte percentage, and neutrophil-to-lymphocyte ration (NLR) were significantly associated with increased time required for CRP normalization. While these variables have previously been shown to be associated with systemic inflammation and surgical site infection, this is the first description of their association with time for CRP normalization in pyogenic spondylitis. It is well known that neutrophils and lymphocytes play key roles in the immune response to bacterial infections. Therefore, these results seem to suggest that a higher percentage of neutrophils may be an indicator for a more severe infection that would take longer to control. Diabetes mellitus was also found to be independently associated with time to CRP normalization. This aligns well with previous studies which have reported high blood glucose levels to be closely linked with an increased risk of postoperative infection. These results suggest the importance of managing blood glucose levels in diabetic patients being treated for pyogenic spondylitis. Lower estimated glomerular filtration rate (eGFR) was also found to be independently associated with a longer time to CRP normalization. In patients with impaired renal function, the antibiotic dosing is often decreased due to the impaired clearance of the antibiotic. Interestingly, the results in this study suggest that the dose adjustment may decrease the effectiveness of the antibiotics for controlling the infection leading to a longer time to CRP normalization. The authors hypothesize that this could shift the first-line therapy in low eGFR patients from cefazolin, which requires a dose adjustment, to something like linezolid which is not metabolized by the kidneys and does not require adjustment, though further studies would be needed to evaluate this directly. A somewhat surprising result of the paper is that neither culture results nor imaging findings were associated with time to CRP normalization. The authors note that contrary to their expectations, identification of the causative organism by culture did not lead to a shorter time for infection control. A possible explanation that was provided is that positive cultures result from a higher abundance of bacteria, so the ability to select a targeted antibiotic therapy shortens what would have been a prolonged treatment, to a length comparable to that of negative-culture cases in which bacterial counts may be lower. One might have also expected that the imaging findings (such as presence of an abscess on MRI or number of vertebral bodies infected) would be associated with length of time for infection control. The fact that these important variables were not found to be significantly associated with time for CRP normalization underscores the importance of the other variables that were found to have an independent association. This finding may also have been affected by the selection of such cases for surgical intervention which helped control these aspects of the infection. Clearly management of pyogenic spondylitis involves complex decision management. The current study helps define variables that correlated with infection CRP normalization, which was used as a marker of infection control. The primary limiting factors were the lack of accounting for surgical intervention and the fact that 23% of the cases never went on to CRP normalization. In summary, this retrospective study by Takahashi et al identifies higher neutrophil percentage, diabetes mellitus, and lower eGFR as independent factors associated with an increased time for CRP normalization in pyogenic spondylitis. The authors conclude that clinicians should be cautious when treating patients with these factors because more time may be required to control their infections.