Concomitant infectious foci in community-acquired bacterial meningitis: the clinical impact of concomitant spondylitis and endocarditis

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Community-acquired bacterial meningitis has been linked to concurrent infectious foci in certain cases. However, reports specifically addressing concomitant infectious foci in patients with community-acquired bacterial meningitis, particularly in recent years, remain scarce. Moreover, the distinct characteristics of various types of concomitant infectious foci in bacterial meningitis cases have yet to be fully elucidated. Methods. We conducted a retrospective analysis of 35 consecutive patients diagnosed with community-acquired bacterial meningitis. We assessed the presence, distribution, and frequency of concomitant infectious foci, followed by an evaluation of the clinical characteristics of patients with these infections. Patients were categorized into two groups based on the period of onset: the early-period group (2004–2013) and the late-period group (2014–2024). Results. Among the 35 patients, 20 (57%) presented with concomitant infections. Based on the site of infection, 7 patients (20%) had sinusitis, 4 (11%) had otitis, 3 (9%) had pneumonia, 8 (24%) had spondylitis, and 4 (12%) had endocarditis. The total number of patients with spondylitis and/or endocarditis was 11 (31%). A significantly higher proportion of patients with concomitant spondylitis and/or endocarditis belonged to the late-period group (82%) compared to those without these infections (38%, P = 0.026). Conclusions. Spondylitis and endocarditis occur as concomitant infectious foci in community-acquired bacterial meningitis, with higher frequency than previously reported, and their incidence has been progressively increasing in recent years. Bacterial meningitis spondylitis endocarditis Introduction Bacterial meningitis is an acute condition characterized by inflammation of the arachnoid and pia mater surrounding the brain and spinal cord, caused by bacterial infection. Despite advances in medical care, its prognosis remains unfavorable, with reported mortality rates ranging from 15% to 35% and rates of long-term sequelae between 10% and 30%.[1] The incidence of bacterial meningitis varies significantly across different geographical regions. In high-income countries, particularly developed nations, incidence rates have declined, reaching 0.9 per 100,000 population, as observed in 2014 in the United States and the Netherland.[2, 3] Community-acquired bacterial meningitis has been associated with concomitant infectious foci in certain cases. Sinusitis, otitis, and pneumonia are relatively common concomitant infections,[1, 3, 4] whereas concomitant spondylitis[5] and endocarditis[6], though infrequent, have also been reported. The presence and type of these concomitant infections play a crucial role in determining treatment strategies and clinical outcomes, highlighting their significance in medical practice. In developed countries, including Japan, rapid societal transformations such as accelerated aging are markedly progressing. Consequently, the demographic and clinical characteristics of bacterial meningitis patients may also be evolving, with potential changes in the presence, location, and frequency of concomitant infectious foci. However, reports specifically addressing concomitant infectious foci in patients with community-acquired bacterial meningitis, particularly in recent years in Japan, remain scarce. Moreover, the distinct characteristics of various types of concomitant infectious foci in bacterial meningitis cases have yet to be fully elucidated. This study aims to investigate the presence, distribution, and frequency of concomitant infectious foci in patients with community-acquired bacterial meningitis. Additionally, we analyzed the clinical characteristics of bacterial meningitis patients with these concomitant infectious foci. Methods Patients We retrospectively evaluated 35 consecutive patients aged 16 years or older who visited Osaka Medical and Pharmaceutical University Hospital and Hirakata City Hospital from January 2004 to December 2024 (21 men, 14 women; mean age 62.9 years). We excluded patients with hospital-acquired meningitis, with a neurosurgical device and those who had undergone neurosurgery or had head traumas within 1 month before the bacterial meningitis. The inclusion criteria of the patients with community bacterial meningitis were having (1) clinical features, such as a headache, fever, and signs of meningeal irritation; (2) positive cerebrospinal fluid (CSF) findings, including pleocytosis (>5mm3, mainly neutrophilic), elevated protein concentrations (>45 mg/dL), and a reduced ratio of CSF glucose to serum glucose (<0.60); (3) a negative CSF stain, culture, or polymerase chain reaction (PCR) for viruses, mycobacteria, and fungi; and (4) a positive CSF culture, smear, or PCR for bacterial pathogens or a good specific response to anti-bacterial therapy.[7] While assessing the presence, location, and frequency of concomitant infectious foci, we excluded secondary infections affecting other organs that were not present at admission but emerged during hospitalization from this definition. For example, patients who had no respiratory symptoms or pulmonary opacities on chest CT at admission but developed these findings three weeks later were not classified as having concomitant infectious foci. Effects of arterial vascular alterations on outcome measured with the Glasgow Outcome Scale (GOS; 1 = death, 2 = vegetative state, 3 = severe disabilities, 4 = moderate disabilities, 5 = no/mild disabilities) were assessed.[8] Patients were divided into two groups based on the onset period: the early-period group (January 2004 to December 2013) and the late-period group (January 2014 to December 2024). This study was conducted according to the 2013 Helsinki Declaration, and the Osaka Medical and Pharmaceutical University Ethics Committee approved the study protocol and the need for informed consent was waived because this was a retrospective study and the data were collected without individual patient identifiers (Approval number #2020-190-1)． Statistical analyses The Mann–Whitney U test was used to assess differences in continuous variables, and the Fisher's exact test was applied to examine categorical variables. The values were expressed as mean ± standard deviation, and a P value of < 0.05 was considered statistically significant. All analyses were performed using the JMP software version 15.0 (SAS Institute Inc., Cary, NC, the USA). Results Background characteristics and causative bacteria of patients with community-acquired bacterial meningitis Table 1 presents the background characteristics and causative bacteria of 35 patients with community-acquired bacterial meningitis. Classification based on disease onset revealed an approximately equal distribution between the early and late phases. The predominant causative pathogens, in descending order, were Streptococcus pneumoniae , Staphylococcus aureus , Streptococcus equisimilis, and Listeria monocytogenes , while the etiology remained unidentified in nearly one-third of the cases. Concomitant infectious foci in patients with community-acquired bacterial meningitis. Table 2 shows concomitant infectious foci in patients with community-acquired bacterial meningitis. Regarding the presence of concomitant infections in other organs among patients with bacterial meningitis, 20 cases (57%) exhibited concomitant infections. Based on the site of infection, 7 patients (20%) had sinusitis, 4 (11%) had otitis, 3 (9%) had pneumonia, 8 (23%) had spondylitis, and 4 (11%) had endocarditis. 9 patients (26%) had at least one of sinusitis or otitis. Among the spondylitis cases, 4 out of 8 patients (11%) also presented with exhibited soft tissue infections in adjacent regions, such as iliopsoas abscesses. The total number of cases with concomitant sinusitis, otitis, and/or pneumonia—conditions previously reported as frequently associated—was 11 (31%). In contrast, the total number of cases with concomitant spondylitis and/or endocarditis—conditions not previously reported as commonly associated—was 11 (31%). In two cases (6%), infections from both categories, those frequently reported as associated and those not commonly reported as such, coexisted, with patients exhibiting at least one condition from each group. Clinical and laboratory features of the patients with community-acquired bacterial meningitis with concomitant spondylitis and/or endocarditis In contrast to previous reports, our study highlighted a higher prevalence of concomitant spondylitis and/or endocarditis in patients with bacterial meningitis. Based on this observation, we classified patients into two groups—those with and those without concomitant spondylitis and/or endocarditis—and performed a comparative analysis (Table 3). Regarding host-related factors, no significant differences were observed between the two groups in terms of sex, age, or underlying diseases. However, when examining the timing of disease onset, the proportion of cases classified as late-onset was significantly greater in the group with concomitant spondylitis and/or endocarditis than in the group without. In terms of laboratory findings, although not statistically significant, patients with concomitant spondylitis and/or endocarditis tended to have a higher rate of positive blood cultures compared to those without. Patients with concomitant spondylitis and/or endocarditis exhibited significantly lower CSF cell counts and neutrophil ratios compared to those without. Concerning the causative pathogens, Staphylococcus aureus was significantly more prevalent in patients with concomitant spondylitis and/or endocarditis. With regard to treatment, the duration of antibiotic therapy was significantly longer in the group with concomitant spondylitis and/or endocarditis. The frequency of surgical intervention was higher in the group with concomitant spondylitis and/or endocarditis, although the difference was not statistically significant. Specifically, surgical procedures were performed in five cases within the group with concomitant spondylitis and/or endocarditis. These included spinal curettage for a patient with spondylitis, laminoplasty, discectomy, and iliopsoas abscess debridement for a patient with both spondylitis and an iliopsoas abscess, mitral and tricuspid valve repair for a patient with both spondylitis and endocarditis, mitral valve repair for a patient with endocarditis, and tricuspid valve replacement for another patient with endocarditis. In contrast, among patients without concomitant spondylitis and/or endocarditis, surgical treatment was performed in four cases. The procedures included myringotomy with drainage for a patient with otitis, sinonasal tumor resection for a patient with sinusitis secondary to a sinonasal tumor, perforation closure for a patient who developed duodenal perforation following meningitis onset, and endoscopic retrograde biliary drainage for a patient who developed cholecystitis, likely resulting from ceftriaxone-associated gallstone formation after meningitis onset. Regarding prognosis, the length of hospital stay was significantly longer in patients with concomitant spondylitis and/or endocarditis. However, no significant difference was observed between the two groups in the Glasgow Outcome Scale scores at discharge. Discussion Our study reveals that concomitant spondylitis and endocarditis occur with remarkable frequency in patients with community-acquired bacterial meningitis, with their incidence being significantly higher than previously reported. In this study, the incidence of concomitant spondylitis reached 23% Although reports on the prevalence of spondylitis in bacterial meningitis are scarce, particularly from large-scale epidemiological studies, a large-scale study conducted in the Netherlands between 2006 and 2018 documented a prevalence of only 0.5% among bacterial meningitis patients.[5] The incidence of concomitant endocarditis in our study was 11%. While data on the frequency of endocarditis in bacterial meningitis remain limited, especially from large-scale epidemiological studies, a previous large-scale study conducted in the Netherlands between 2006 and 2012 reported a prevalence of merely 2% among bacterial meningitis patients.[6] In contrast, the incidence of concomitant sinusitis, otitis, and pneumonia in patients with bacterial meningitis was comparable to previous reports. In our study, the incidence of concomitant sinusitis, otitis, or at least one of these conditions in bacterial meningitis was 20%, 11%, and 26%, respectively. Although studies specifically examining the incidence of sinusitis alone in bacterial meningitis are limited, previous research has reported an incidence of concomitant otitis ranging from 15% to 21%[9-12] and an incidence of at least one of sinusitis or otitis between 20% and 34%[1, 3, 13]. Similarly, in the present study, the incidence of pneumonia among bacterial meningitis patients was 9%, aligning with prior reports indicating a prevalence of 8% to 19%.[1, 3, 14-19] Our study highlights a recent increase in the prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients, as evidenced by a higher prevalence in the late-period group (2014–2024) compared to the early-period group (2004–2013). This increasing trend is consistent with the observation that the incidence of these infections in our study was higher than that reported in previous studies completed prior to the end of our study period.[5, 6] In recent years, an increasing incidence of pyogenic spondylitis and infective endocarditis has been documented.[20-22] This trend may have contributed to a rise in bacterial meningitis cases secondary to these infections, potentially influencing the observed increase in spondylitis and endocarditis as concomitant infections in bacterial meningitis patients. However, our study found no significant differences in age, sex, or underlying comorbidities between patients with and without spondylitis and/or endocarditis, suggesting that host-related predisposing factors for these infections remain unidentified. Consequently, the underlying reasons for the increasing prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients remain unclear. In our study, bacterial meningitis accompanied by concomitant spondylitis and/or endocarditis demonstrated a less pronounced elevation in CSF cell count and neutrophil ratio compared to bacterial meningitis without these conditions. This observation can be explained by previous reports indicating that bacterial meningitis with a modest increase in CSF cell count is associated with excessive bacterial growth, bacteremia, sepsis, and other systemic complications.[23-26] Consistent with the findings in our study, bacterial meningitis with concomitant endocarditis has been shown to exhibit lower CSF inflammatory markers, including a reduced white blood cell count.[6] In contrast, no large-scale studies have specifically examined the CSF findings in bacterial meningitis with concomitant spondylitis. However, as this condition has been reported to predominantly result from hematogenous spread of bacteria,[5] it is likely associated with bacteremia, which, in turn, may correlate with a modest increase in CSF cell count. Moreover, some cases of this condition are believed to arise from spondylitis triggering an inflammatory response in the CSF through the development of a paraspinal or epidural abscess, in which case the inflammatory reaction in meningitis is suggested to be mild.[5] Based on these findings, in cases of bacterial meningitis with mild cerebrospinal fluid abnormalities, clinicians should not be reassured by the seemingly benign presentation but should exercise heightened vigilance for potential concomitant infection foci and conduct thorough investigations to ensure timely diagnosis and appropriate management. Our data further indicate that in bacterial meningitis, Staphylococcus aureus is predominantly responsible for cases with concomitant spondylitis and/or endocarditis, in agreement with prior studies.[27] In our cohort, Staphylococcus aureus was identified as the causative agent in 9% of all bacterial meningitis cases. However, this prevalence increased to 27% when considering only those with concomitant spondylitis and/or endocarditis. Previous studies have documented similar findings, with the prevalence of Staphylococcus aureus in bacterial meningitis ranging from 1% to 9% overall,[3, 17, 28, 29] and higher rates observed in cases with concomitant spondylitis (30%)[5] and endocarditis (33%)[6]. From the perspective of Staphylococcus aureus meningitis, although our study identified only three cases, all were associated with either spondylitis or endocarditis—two with spondylitis and one with endocarditis. The high prevalence of these concomitant conditions in our cohort is consistent with earlier reports, which have noted rates of 39–60% for spondylitis and 25–56% for endocarditis.[27, 30-35] In cases of bacterial meningitis, particularly when Staphylococcus aureus is the implicated pathogen, it is crucial to consider the possibility of concomitant spondylitis and/or endocarditis. Our results also show that among patients with bacterial meningitis, those with concomitant spondylitis and/or endocarditis have a longer duration of antibiotic therapy and tend to have a higher frequency of surgical intervention compared to those without these concomitant conditions, with the types and specifics of the surgeries differing between the groups as expected. In consistent with our findings, the general recommendation for the duration of antibiotic treatment in patients with both endocarditis and meningitis ranges from 4 to 6 weeks,[6] which is significantly longer than the standard 10 to 14 days for meningitis without systemic infections.[36] Although we could not find standard duration for antibiotic therapy in patients with both spondylitis and meningitis, treatment for isolated spondylitis alone often exceeds 6 months, much longer than for isolated meningitis.[37] An increased risk for surgical intervention has also been reported patients with bacterial meningitis who develop concomitant spondylitis[5] and endocarditis[6]. Moreover, while our findings did not indicate an association between the presence of spondylitis and/or endocarditis with poor prognosis in bacterial meningitis, previous studies have suggested that the presence of endocarditis may contribute to adverse outcomes.[6] This study has several limitations that should be considered. In particular, it is a retrospective analysis based on cases from only two hospitals, with a limited sample size. As a result, the extent to which these findings —especially a recent increase in the prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients—can be extrapolated to the broader Japanese population, other developed nations, or the global context remains unclear. Future multicenter prospective studies with larger sample sizes are warranted. Conclusion Spondylitis and endocarditis occur as concomitant infectious foci in community-acquired bacterial meningitis, with higher frequency than previously reported, and their incidence has been progressively increasing in recent years. Bacterial meningitis with concomitant spondylitis and/or endocarditis is characterized by a milder elevation in cerebrospinal fluid cell count and neutrophil proportion, along with a higher likelihood of Staphylococcus aureus as the causative pathogen. In such cases, we maintain a high index of suspicion for these infectious foci and perform comprehensive diagnostic evaluations to facilitate prompt identification and optimal management. Abbreviations CSF cerebrospinal fluid Declarations Ethics approval and consent to participate This study involves human participants and was approved by the Osaka Medical and Pharmaceutical University Ethics Committee (Approval number #2020-190-1). The need for informed consent was waived because this was a retrospective study and the data were collected without individual patient identifiers. Clinical trial number Not applicable. Consent for publication Not applicable. Availability of date and material Data will be made upon reasonable request to the corresponding author. Competing interests The authors declare no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Author Contribution T.H. designed the study, carried out the acquisition of data, analyzed the data, and wrote the manuscript. S.O. carried out the acquisition of data. T.S. carried out the acquisition of data. Y.Y. carried out the acquisition of data. Y.N. carried out the acquisition of data. S.O. carried out the acquisition of data. T.H. carried out the acquisition of data. H.N. proposed the initial concept of the study. S.A. supervised and revised the manuscript. All authors reviewed the manuscript. Acknowledgments None. Data Availability Data will be made upon reasonable request to the corresponding author. References van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M: Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004, 351(18):1849-1859. Hasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, Zimmer L, Ginocchio CC: Epidemiology of Meningitis and Encephalitis in the United States, 2011-2014. Clin Infect Dis 2017, 65(3):359-363. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, Kloek AT, Lucas MJ, Tanck MW, van der Ende A, van de Beek D: Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2016, 16(3):339-347. Figueiredo AHA, Brouwer MC, Bijlsma MW, van der Ende A, van de Beek D: Community-acquired pneumonia in patients with bacterial meningitis: a prospective nationwide cohort study. 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Chang WN, Lu CH, Wu JJ, Chang HW, Tsai YC, Chen FT, Chien CC: Staphylococcus aureus meningitis in adults: a clinical comparison of infections caused by methicillin-resistant and methicillin-sensitive strains. Infection 2001, 29(5):245-250. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR: Advances in treatment of bacterial meningitis. Lancet 2012, 380(9854):1693-1702. McHenry MC, Easley KA, Locker GA: Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis 2002, 34(10):1342-1350. Tables Table 1. Background characteristics and causative bacteria of 35 patients with community-acquired bacterial meningitis. Variables Age (years), mean ± SD 62.9 ± 13.8 Male: female ratio 21:14 University Hospital: City Hospital case ratio 24: 11 The early-period: late-period ratio 17:18 Causative bacteria, n (%) Streptococcus pneumoniae 11 (31) Staphylococcus aureus 3 (9) Streptococcus equisimilis 3 (9) Listeria monocytogenes 2 (6) Streptococcus agalactiae 1 (3) Streptococcus salivarius 1 (3) Streptococcus sanguinis 1 (3) Klebsiella pneumoniae 1 (3) Actinomyces species 1 (3) Undefined 11 (31) SD, standard deviation. Table 2. Concomitant infectious foci in 35 patients with community-acquired bacterial meningitis. Concomitant infectious foci n (%) Sinusitis 7 (20) Otitis 4 (11) Pneumonia 3 (9) Spondylitis 8 (23) With adjacent soft tissue infection (e.g., psoas abscess) 4 (11) Endocarditis 4 (11) Sinusitis, otitis, and/or pneumonia 11 (31) Spondylitis and/or endocarditis 11 (31) Any infectious foci 20 (57) Table 3. Clinical and laboratory features of 35 patients with community-acquired bacterial meningitis with and without concomitant endocarditis and/or spondylitis Patients with concomitant endocarditis and/or spondylitis (n = 11) Patients without concomitant endocarditis and/or spondylitis (n = 24) P-value Age (years), mean ± SD 61.5 ± 10.6 63.6 ± 15.1 NS Male, n (%) 7 (64) 14 (58) NS University Hospital case, n (%) 8 (73) 16 (67) NS The late-period, n (%) 9 (82) 9 (38) 0.026 Immunocompromised state, n (%) Diabetes mellitus 2 (18) 6 (25) NS Cancer 0 (0) 4 (17) NS Receiving immunosuppressants or steroids 0 (0) 3 (13) NS Renal failure and/or hepatic failure 0 (0) 2 (8) NS Any of the above 2 (18) 11 (46) NS Causative bacteria, n (%) Streptococcus pneumoniae 3 (27) 8 (33) NS Staphylococcus aureus 3 (27) 0 (0) 0.025 Streptococcus species * 3 (27) 3 (13) NS Other bacteria 1 (9) 3 (13) NS Undefined 1 (9) 7 (29) NS Blood examination, mean ± SD WBC (/μl) 13397 ± 6278 15670 ± 9084 CRP (mg/dl) 20.4 ± 9.3 14.1 ± 11.9 Positive blood culture, n/N (%) 9/11 (82) 10/19 (53) NS CSF examination, mean ± SD Cell count (/μl) 852 ± 1899 7741 ± 14008 0.003 Percentage of neutrophils (%) 47.1 ± 30.7 74.1 ± 25.7 0.012 Protein (mg/dl) 468 ± 817 337 ± 235 NS Duration of antibiotic therapy (days), mean ± SD 173 ± 211.5 30.5 ± 17.6 <0.0001 Hospitalization length of stay (days), mean ± SD 88.9 ± 40.5 49.9 ± 33.5 0.005 Glasgow Outcome Scale Score, n (%) NS 1 (Death) 0 (0) 1 (4) 2 (Vegetable state) 0 (0) 0 (0) 3 (Severely disabled) 4 (36) 8 (33) 4 (Moderately disabled) 4 (36) 8 (33) 5 (Mild or no disability) 3 (27) 7 (29) * Streptococcus equisimilis, Streptococcus agalactiae, Streptococcus salivarius, and Streptococcus sanguinis CRP, C-reactive protein; CSF, cerebrospinal fluid; NS, not significant; SD, standard deviation; WBC, white blood cell count. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Dec, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 08 Oct, 2025 Reviews received at journal 02 Sep, 2025 Reviewers agreed at journal 06 Aug, 2025 Reviews received at journal 05 Aug, 2025 Reviewers agreed at journal 27 Jul, 2025 Reviewers invited by journal 13 Jul, 2025 Editor invited by journal 10 Jul, 2025 Editor assigned by journal 09 Jul, 2025 Submission checks completed at journal 09 Jul, 2025 First submitted to journal 05 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7055324","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485875753,"identity":"f04cbbe2-4b38-4c2e-bbdb-2ac579146106","order_by":0,"name":"Takafumi Hosokawa","email":"data:image/png;base64,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","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Takafumi","middleName":"","lastName":"Hosokawa","suffix":""},{"id":485875754,"identity":"ce45ea4c-1892-478f-8d31-146c8e6d7958","order_by":1,"name":"Shoji Ogawa","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Shoji","middleName":"","lastName":"Ogawa","suffix":""},{"id":485875755,"identity":"1f6786a0-c903-4268-b819-103577c84211","order_by":2,"name":"Taiki Sawai","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Taiki","middleName":"","lastName":"Sawai","suffix":""},{"id":485875756,"identity":"3401d5cd-5352-4241-82f3-b6a233e7516d","order_by":3,"name":"Yukiyo Yoshimoto","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Yukiyo","middleName":"","lastName":"Yoshimoto","suffix":""},{"id":485875757,"identity":"9ffac64f-7f49-4863-8cd3-2c237c45bc2b","order_by":4,"name":"Yoshitsugu Nakamura","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Yoshitsugu","middleName":"","lastName":"Nakamura","suffix":""},{"id":485875758,"identity":"dee0899b-3747-43e4-97d9-98f7f76bd952","order_by":5,"name":"Shin Ota","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Shin","middleName":"","lastName":"Ota","suffix":""},{"id":485875759,"identity":"17f19cef-b805-4ac1-b6c6-efd5c69fa651","order_by":6,"name":"Takahiko Hirose","email":"","orcid":"","institution":"Hirakata City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takahiko","middleName":"","lastName":"Hirose","suffix":""},{"id":485875760,"identity":"76c379db-91e0-48cc-b53a-a7388d2e3f8d","order_by":7,"name":"Hideto Nakajima","email":"","orcid":"","institution":"Nihon University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hideto","middleName":"","lastName":"Nakajima","suffix":""},{"id":485875761,"identity":"ee440399-21cf-492a-8637-666a8c36276e","order_by":8,"name":"Shigeki Arawaka","email":"","orcid":"","institution":"Osaka Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Shigeki","middleName":"","lastName":"Arawaka","suffix":""}],"badges":[],"createdAt":"2025-07-06 01:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7055324/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7055324/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-12448-3","type":"published","date":"2025-12-26T15:58:36+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":99172433,"identity":"420bdc61-64d1-4a62-a6b8-c6eb9a2fc232","added_by":"auto","created_at":"2025-12-29 16:09:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":737840,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7055324/v1/9c221539-21f6-4cb3-b3e7-66df16c098b0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Concomitant infectious foci in community-acquired bacterial meningitis: the clinical impact of concomitant spondylitis and endocarditis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBacterial meningitis is an acute condition characterized by inflammation of the arachnoid and pia mater surrounding the brain and spinal cord, caused by bacterial infection. Despite advances in medical care, its prognosis remains unfavorable, with reported mortality rates ranging from 15% to 35% and rates of long-term sequelae between 10% and 30%.[1] The incidence of bacterial meningitis varies significantly across different geographical regions. In high-income countries, particularly developed nations, incidence rates have declined, reaching 0.9 per 100,000 population, as observed in 2014 in the United States and the Netherland.[2, 3]\u003c/p\u003e\n\u003cp\u003eCommunity-acquired bacterial meningitis has been associated with concomitant infectious foci in certain cases. Sinusitis, otitis, and pneumonia are relatively common concomitant infections,[1, 3, 4] whereas concomitant spondylitis[5] and endocarditis[6], though infrequent, have also been reported. The presence and type of these concomitant infections play a crucial role in determining treatment strategies and clinical outcomes, highlighting their significance in medical practice. In developed countries, including Japan, rapid societal transformations such as accelerated aging are markedly progressing. Consequently, the demographic and clinical characteristics of bacterial meningitis patients may also be evolving, with potential changes in the presence, location, and frequency of concomitant infectious foci. However, reports specifically addressing concomitant infectious foci in patients with community-acquired bacterial meningitis, particularly in recent years in Japan, remain scarce. Moreover, the distinct characteristics of various types of concomitant infectious foci in bacterial meningitis cases have yet to be fully elucidated.\u003c/p\u003e\n\u003cp\u003eThis study aims to investigate the presence, distribution, and frequency of concomitant infectious foci in patients with community-acquired bacterial meningitis. Additionally, we analyzed the clinical characteristics of bacterial meningitis patients with these concomitant infectious foci.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively evaluated 35 consecutive patients aged 16 years or older who visited Osaka Medical and Pharmaceutical University Hospital and Hirakata City Hospital from January 2004 to December 2024 (21 men, 14 women; mean age 62.9 years). We excluded patients with hospital-acquired meningitis, with a neurosurgical device and those who had undergone neurosurgery or had head traumas within 1 month before the bacterial meningitis.\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria of the patients with community bacterial meningitis were having (1) clinical features, such as a headache, fever, and signs of meningeal irritation; (2) positive cerebrospinal fluid (CSF) findings, including pleocytosis (\u0026gt;5mm3, mainly neutrophilic), elevated protein concentrations (\u0026gt;45 mg/dL), and a reduced ratio of CSF glucose to serum glucose (\u0026lt;0.60); (3) a negative CSF stain, culture, or polymerase chain reaction (PCR) for viruses, mycobacteria, and fungi; and (4) a positive CSF culture, smear, or PCR for bacterial pathogens or a good specific response to anti-bacterial therapy.[7]\u003c/p\u003e\n\u003cp\u003eWhile assessing the presence, location, and frequency of concomitant infectious foci, we excluded secondary infections affecting other organs that were not present at admission but emerged during hospitalization from this definition. For example, patients who had no respiratory symptoms or pulmonary opacities on chest CT at admission but developed these findings three weeks later were not classified as having concomitant infectious foci.\u003c/p\u003e\n\u003cp\u003eEffects of arterial vascular alterations on outcome measured with the Glasgow Outcome Scale (GOS; 1 = death, 2 = vegetative state, 3 = severe disabilities, 4 = moderate disabilities, 5 = no/mild disabilities) were assessed.[8] Patients were divided into two groups based on the onset period: the early-period group (January 2004 to December 2013) and the late-period group (January 2014 to December 2024).\u003c/p\u003e\n\u003cp\u003eThis study was conducted according to the 2013 Helsinki Declaration, and the Osaka Medical and Pharmaceutical University Ethics Committee approved the study protocol and the need for informed consent was waived because this was a retrospective study and the data were collected without individual patient identifiers (Approval number #2020-190-1)．\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Mann\u0026ndash;Whitney U test was used to assess differences in continuous variables, and the Fisher\u0026apos;s exact test was applied to examine categorical variables. The values were expressed as mean \u0026plusmn; standard deviation, and a P value of \u0026lt; 0.05 was considered statistically significant. All analyses were performed using the JMP software version 15.0 (SAS Institute Inc., Cary, NC, the USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBackground characteristics and causative bacteria of patients with community-acquired bacterial meningitis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 presents the background characteristics and causative bacteria of 35 patients with community-acquired bacterial meningitis. Classification based on disease onset revealed an approximately equal distribution between the early and late phases. The predominant causative pathogens, in descending order, were \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eStreptococcus equisimilis, and Listeria monocytogenes\u003c/em\u003e, while the etiology remained unidentified in nearly one-third of the cases. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcomitant infectious foci in patients with community-acquired bacterial meningitis.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows concomitant infectious foci in patients with community-acquired bacterial meningitis. Regarding the presence of concomitant infections in other organs among patients with bacterial meningitis, 20 cases (57%) exhibited concomitant infections. Based on the site of infection, 7 patients (20%) had sinusitis, 4 (11%) had otitis, 3 (9%) had pneumonia, 8 (23%) had spondylitis, and 4 (11%) had endocarditis. 9 patients (26%) had at least one of sinusitis or otitis. Among the spondylitis cases, 4 out of 8 patients (11%) also presented with exhibited soft tissue infections in adjacent regions, such as iliopsoas abscesses. \u003c/p\u003e\n\u003cp\u003eThe total number of cases with concomitant sinusitis, otitis, and/or pneumonia\u0026mdash;conditions previously reported as frequently associated\u0026mdash;was 11 (31%). In contrast, the total number of cases with concomitant spondylitis and/or endocarditis\u0026mdash;conditions not previously reported as commonly associated\u0026mdash;was 11 (31%). In two cases (6%), infections from both categories, those frequently reported as associated and those not commonly reported as such, coexisted, with patients exhibiting at least one condition from each group. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical and laboratory features of the patients with community-acquired bacterial meningitis with concomitant spondylitis and/or endocarditis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn contrast to previous reports, our study highlighted a higher prevalence of concomitant spondylitis and/or endocarditis in patients with bacterial meningitis. Based on this observation, we classified patients into two groups\u0026mdash;those with and those without concomitant spondylitis and/or endocarditis\u0026mdash;and performed a comparative analysis (Table 3).\u003c/p\u003e\n\u003cp\u003eRegarding host-related factors, no significant differences were observed between the two groups in terms of sex, age, or underlying diseases. However, when examining the timing of disease onset, the proportion of cases classified as late-onset was significantly greater in the group with concomitant spondylitis and/or endocarditis than in the group without.\u003c/p\u003e\n\u003cp\u003eIn terms of laboratory findings, although not statistically significant, patients with concomitant spondylitis and/or endocarditis tended to have a higher rate of positive blood cultures compared to those without. Patients with concomitant spondylitis and/or endocarditis exhibited significantly lower CSF cell counts and neutrophil ratios compared to those without. Concerning the causative pathogens, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was significantly more prevalent in patients with concomitant spondylitis and/or endocarditis.\u003c/p\u003e\n\u003cp\u003eWith regard to treatment, the duration of antibiotic therapy was significantly longer in the group with concomitant spondylitis and/or endocarditis. The frequency of surgical intervention was higher in the group with concomitant spondylitis and/or endocarditis, although the difference was not statistically significant. Specifically, surgical procedures were performed in five cases within the group with concomitant spondylitis and/or endocarditis. These included spinal curettage for a patient with spondylitis, laminoplasty, discectomy, and iliopsoas abscess debridement for a patient with both spondylitis and an iliopsoas abscess, mitral and tricuspid valve repair for a patient with both spondylitis and endocarditis, mitral valve repair for a patient with endocarditis, and tricuspid valve replacement for another patient with endocarditis. In contrast, among patients without concomitant spondylitis and/or endocarditis, surgical treatment was performed in four cases. The procedures included myringotomy with drainage for a patient with otitis, sinonasal tumor resection for a patient with sinusitis secondary to a sinonasal tumor, perforation closure for a patient who developed duodenal perforation following meningitis onset, and endoscopic retrograde biliary drainage for a patient who developed cholecystitis, likely resulting from ceftriaxone-associated gallstone formation after meningitis onset.\u003c/p\u003e\n\u003cp\u003eRegarding prognosis, the length of hospital stay was significantly longer in patients with concomitant spondylitis and/or endocarditis. However, no significant difference was observed between the two groups in the Glasgow Outcome Scale scores at discharge.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study reveals that concomitant spondylitis and endocarditis occur with remarkable frequency in patients with community-acquired bacterial meningitis, with their incidence being significantly higher than previously reported. In this study, the incidence of concomitant spondylitis reached 23% Although reports on the prevalence of spondylitis in bacterial meningitis are scarce, particularly from large-scale epidemiological studies, a large-scale study conducted in the Netherlands between 2006 and 2018 documented a prevalence of only 0.5% among bacterial meningitis patients.[5] The incidence of concomitant endocarditis in our study was 11%. While data on the frequency of endocarditis in bacterial meningitis remain limited, especially from large-scale epidemiological studies, a previous large-scale study conducted in the Netherlands between 2006 and 2012 reported a prevalence of merely 2% among bacterial meningitis patients.[6] In contrast, the incidence of concomitant sinusitis, otitis, and pneumonia in patients with bacterial meningitis was comparable to previous reports. In our study, the incidence of concomitant sinusitis, otitis, or at least one of these conditions in bacterial meningitis was 20%, 11%, and 26%, respectively. Although studies specifically examining the incidence of sinusitis alone in bacterial meningitis are limited, previous research has reported an incidence of concomitant otitis ranging from 15% to 21%[9-12] and an incidence of at least one of sinusitis or otitis between 20% and 34%[1, 3, 13]. Similarly, in the present study, the incidence of pneumonia among bacterial meningitis patients was 9%, aligning with prior reports indicating a prevalence of 8% to 19%.[1, 3, 14-19]\u003c/p\u003e\n\u003cp\u003eOur study highlights a recent increase in the prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients, as evidenced by a higher prevalence in the late-period group (2014\u0026ndash;2024) compared to the early-period group (2004\u0026ndash;2013). This increasing trend is consistent with the observation that the incidence of these infections in our study was higher than that reported in previous studies completed prior to the end of our study period.[5, 6] In recent years, an increasing incidence of pyogenic spondylitis and infective endocarditis has been documented.[20-22] This trend may have contributed to a rise in bacterial meningitis cases secondary to these infections, potentially influencing the observed increase in spondylitis and endocarditis as concomitant infections in bacterial meningitis patients. However, our study found no significant differences in age, sex, or underlying comorbidities between patients with and without spondylitis and/or endocarditis, suggesting that host-related predisposing factors for these infections remain unidentified. Consequently, the underlying reasons for the increasing prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients remain unclear.\u003c/p\u003e\n\u003cp\u003eIn our study, bacterial meningitis accompanied by concomitant spondylitis and/or endocarditis demonstrated a less pronounced elevation in CSF cell count and neutrophil ratio compared to bacterial meningitis without these conditions. This observation can be explained by previous reports indicating that bacterial meningitis with a modest increase in CSF cell count is associated with excessive bacterial growth, bacteremia, sepsis, and other systemic complications.[23-26] Consistent with the findings in our study, bacterial meningitis with concomitant endocarditis has been shown to exhibit lower CSF inflammatory markers, including a reduced white blood cell count.[6] In contrast, no large-scale studies have specifically examined the CSF findings in bacterial meningitis with concomitant spondylitis. However, as this condition has been reported to predominantly result from hematogenous spread of bacteria,[5] it is likely associated with bacteremia, which, in turn, may correlate with a modest increase in CSF cell count. Moreover, some cases of this condition are believed to arise from spondylitis triggering an inflammatory response in the CSF through the development of a paraspinal or epidural abscess, in which case the inflammatory reaction in meningitis is suggested to be mild.[5] Based on these findings, in cases of bacterial meningitis with mild cerebrospinal fluid abnormalities, clinicians should not be reassured by the seemingly benign presentation but should exercise heightened vigilance for potential concomitant infection foci and conduct thorough investigations to ensure timely diagnosis and appropriate management. \u003c/p\u003e\n\u003cp\u003eOur data further indicate that in bacterial meningitis, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is predominantly responsible for cases with concomitant spondylitis and/or endocarditis, in agreement with prior studies.[27] In our cohort, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was identified as the causative agent in 9% of all bacterial meningitis cases. However, this prevalence increased to 27% when considering only those with concomitant spondylitis and/or endocarditis. Previous studies have documented similar findings, with the prevalence of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e in bacterial meningitis ranging from 1% to 9% overall,[3, 17, 28, 29] and higher rates observed in cases with concomitant spondylitis (30%)[5] and endocarditis (33%)[6]. From the perspective of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e meningitis, although our study identified only three cases, all were associated with either spondylitis or endocarditis\u0026mdash;two with spondylitis and one with endocarditis. The high prevalence of these concomitant conditions in our cohort is consistent with earlier reports, which have noted rates of 39\u0026ndash;60% for spondylitis and 25\u0026ndash;56% for endocarditis.[27, 30-35] In cases of bacterial meningitis, particularly when \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is the implicated pathogen, it is crucial to consider the possibility of concomitant spondylitis and/or endocarditis.\u003c/p\u003e\n\u003cp\u003eOur results also show that among patients with bacterial meningitis, those with concomitant spondylitis and/or endocarditis have a longer duration of antibiotic therapy and tend to have a higher frequency of surgical intervention compared to those without these concomitant conditions, with the types and specifics of the surgeries differing between the groups as expected. In consistent with our findings, the general recommendation for the duration of antibiotic treatment in patients with both endocarditis and meningitis ranges from 4 to 6 weeks,[6] which is significantly longer than the standard 10 to 14 days for meningitis without systemic infections.[36] Although we could not find standard duration for antibiotic therapy in patients with both spondylitis and meningitis, treatment for isolated spondylitis alone often exceeds 6 months, much longer than for isolated meningitis.[37] An increased risk for surgical intervention has also been reported patients with bacterial meningitis who develop concomitant spondylitis[5] and endocarditis[6]. Moreover, while our findings did not indicate an association between the presence of spondylitis and/or endocarditis with poor prognosis in bacterial meningitis, previous studies have suggested that the presence of endocarditis may contribute to adverse outcomes.[6]\u003c/p\u003e\n\u003cp\u003eThis study has several limitations that should be considered. In particular, it is a retrospective analysis based on cases from only two hospitals, with a limited sample size. As a result, the extent to which these findings \u0026mdash;especially a recent increase in the prevalence of spondylitis and/or endocarditis as concomitant infections in bacterial meningitis patients\u0026mdash;can be extrapolated to the broader Japanese population, other developed nations, or the global context remains unclear. Future multicenter prospective studies with larger sample sizes are warranted.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSpondylitis and endocarditis occur as concomitant infectious foci in community-acquired bacterial meningitis, with higher frequency than previously reported, and their incidence has been progressively increasing in recent years. Bacterial meningitis with concomitant spondylitis and/or endocarditis is characterized by a milder elevation in cerebrospinal fluid cell count and neutrophil proportion, along with a higher likelihood of Staphylococcus aureus as the causative pathogen. In such cases, we maintain a high index of suspicion for these infectious foci and perform comprehensive diagnostic evaluations to facilitate prompt identification and optimal management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCSF \u0026nbsp;cerebrospinal fluid\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study involves human participants and was approved by the Osaka Medical and Pharmaceutical University Ethics Committee (Approval number #2020-190-1). The need for informed consent was waived because this was a retrospective study and the data were collected without individual patient identifiers.\u003c/p\u003e\n\u003ch2\u003eClinical trial number\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAvailability of date and material\u003c/h2\u003e\n\u003cp\u003eData will be made upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eT.H. designed the study, carried out the acquisition of data, analyzed the data, and wrote the manuscript. S.O. carried out the acquisition of data. T.S. carried out the acquisition of data. Y.Y. carried out the acquisition of data. Y.N. carried out the acquisition of data. S.O. carried out the acquisition of data. T.H. carried out the acquisition of data. H.N. proposed the initial concept of the study. S.A. supervised and revised the manuscript. All authors reviewed the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgments\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eData will be made upon reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003evan de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M: Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004, 351(18):1849-1859.\u003c/li\u003e\n\u003cli\u003eHasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, Zimmer L, Ginocchio CC: Epidemiology of Meningitis and Encephalitis in the United States, 2011-2014. Clin Infect Dis 2017, 65(3):359-363.\u003c/li\u003e\n\u003cli\u003eBijlsma MW, Brouwer MC, Kasanmoentalib ES, Kloek AT, Lucas MJ, Tanck MW, van der Ende A, van de Beek D: Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2016, 16(3):339-347.\u003c/li\u003e\n\u003cli\u003eFigueiredo AHA, Brouwer MC, Bijlsma MW, van der Ende A, van de Beek D: Community-acquired pneumonia in patients with bacterial meningitis: a prospective nationwide cohort study. Clin Microbiol Infect 2020, 26(4):513 e517-513 e511.\u003c/li\u003e\n\u003cli\u003eSheybani F, Figueiredo AHA, Brouwer MC, van de Beek D: Vertebral osteomyelitis in bacterial meningitis patients. Int J Infect Dis 2021, 111:354-359.\u003c/li\u003e\n\u003cli\u003eLucas MJ, Brouwer MC, van der Ende A, van de Beek D: Endocarditis in adults with bacterial meningitis. Circulation 2013, 127(20):2056-2062.\u003c/li\u003e\n\u003cli\u003eRopper AH ARAaVs: principles of neurology. 8th ed. 2005. p. 631\u0026ndash;56. Division.\u003c/li\u003e\n\u003cli\u003eJennett B, Teasdale G, Braakman R, Minderhoud J, Knill-Jones R: Predicting outcome in individual patients after severe head injury. Lancet 1976, 1(7968):1031-1034.\u003c/li\u003e\n\u003cli\u003eRanzenigo M, van Soest TM, Hensen EF, Cinque P, Castagna A, Brouwer MC, van de Beek D: Otitis in Patients With Community-Acquired Bacterial Meningitis: A Nationwide Prospective Cohort Study. Clin Infect Dis 2024, 79(2):329-335.\u003c/li\u003e\n\u003cli\u003eIbrahim SI, Cheang PP, Nunez DA: Incidence of meningitis secondary to suppurative otitis media in adults. J Laryngol Otol 2010, 124(11):1158-1161.\u003c/li\u003e\n\u003cli\u003eGeyik MF, Kokoglu OF, Hosoglu S, Ayaz C: Acute bacterial meningitis as a complication of otitis media and related mortality factors. Yonsei Med J 2002, 43(5):573-578.\u003c/li\u003e\n\u003cli\u003eFlores-Cordero JM, Amaya-Villar R, Rincon-Ferrari MD, Leal-Noval SR, Garnacho-Montero J, Llanos-Rodriguez AC, Murillo-Cabezas F: Acute community-acquired bacterial meningitis in adults admitted to the intensive care unit: clinical manifestations, management and prognostic factors. Intensive Care Med 2003, 29(11):1967-1973.\u003c/li\u003e\n\u003cli\u003eLesnakova A, Holeckova K, Kolenova A, Streharova A, Kisac P, Beno P, Kalavsky E, Sramka M, Ondrusova A, Benca J et al: Bacterial meningitis after sinusitis and otitis media: ear, nose, throat infections are still the commonest risk factors for the community acquired meningitis. Neuro Endocrinol Lett 2007, 28 Suppl 3:14-15.\u003c/li\u003e\n\u003cli\u003evan de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E: Community-acquired bacterial meningitis. Nat Rev Dis Primers 2016, 2:16074.\u003c/li\u003e\n\u003cli\u003eBackhaus E, Berg S, Andersson R, Ockborn G, Malmstrom P, Dahl M, Nasic S, Trollfors B: Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors. BMC Infect Dis 2016, 16:367.\u003c/li\u003e\n\u003cli\u003eDauchy FA, Gruson D, Chene G, Viot J, Bebear C, Maugein J, Bezian MC, Dutronc H, Dupon M: Prognostic factors in adult community-acquired bacterial meningitis: a 4-year retrospective study. Eur J Clin Microbiol Infect Dis 2007, 26(10):743-746.\u003c/li\u003e\n\u003cli\u003eDurand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS, Jr., Swartz MN: Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993, 328(1):21-28.\u003c/li\u003e\n\u003cli\u003eMourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D et al: Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA 2013, 310(20):2174-2183.\u003c/li\u003e\n\u003cli\u003eSwartz MN, Dodge PR: Bacterial Meningitis--a Review of Selected Aspects. I. General Clinical Features, Special Problems and Unusual Meningeal Reactions Mimicking Bacterial Meningitis. N Engl J Med 1965, 272:898-902 CONTD.\u003c/li\u003e\n\u003cli\u003eChen H, Zhan Y, Zhang K, Gao Y, Chen L, Zhan J, Chen Z, Zeng Z: The Global, Regional, and National Burden and Trends of Infective Endocarditis From 1990 to 2019: Results From the Global Burden of Disease Study 2019. Front Med (Lausanne) 2022, 9:774224.\u003c/li\u003e\n\u003cli\u003eCheung WY, Luk KD: Pyogenic spondylitis. Int Orthop 2012, 36(2):397-404.\u003c/li\u003e\n\u003cli\u003eMarchionni E, Marconi L, Ruinato D, Zamparini E, Gasbarrini A, Viale P: Spondylodiscitis: is really all well defined? Eur Rev Med Pharmacol Sci 2019, 23(2 Suppl):201-209.\u003c/li\u003e\n\u003cli\u003eTauber MG, Kennedy SL, Tureen JH, Lowenstein DH: Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein. Am J Pathol 1992, 141(1):53-60.\u003c/li\u003e\n\u003cli\u003eWeisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J: Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study. BMC Infect Dis 2006, 6:149.\u003c/li\u003e\n\u003cli\u003eKastenbauer S, Pfister HW: Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain 2003, 126(Pt 5):1015-1025.\u003c/li\u003e\n\u003cli\u003eMcMillan DA, Lin CY, Aronin SI, Quagliarello VJ: Community-acquired bacterial meningitis in adults: categorization of causes and timing of death. Clin Infect Dis 2001, 33(7):969-975.\u003c/li\u003e\n\u003cli\u003evan Soest TM, Sondermolle MB, Brouwer MC, Chekrouni N, Larsen AR, Petersen A, van Sorge NM, Nielsen H, van de Beek D, Bodilsen J et al: Community-acquired Staphylococcus aureus meningitis in adults. J Infect 2023, 86(3):239-244.\u003c/li\u003e\n\u003cli\u003eSchlesinger LS, Ross SC, Schaberg DR: Staphylococcus aureus meningitis: a broad-based epidemiologic study. Medicine (Baltimore) 1987, 66(2):148-156.\u003c/li\u003e\n\u003cli\u003eJensen AG, Espersen F, Skinhoj P, Rosdahl VT, Frimodt-Moller N: Staphylococcus aureus meningitis. A review of 104 nationwide, consecutive cases. Arch Intern Med 1993, 153(16):1902-1908.\u003c/li\u003e\n\u003cli\u003ePedersen M, Benfield TL, Skinhoej P, Jensen AG: Haematogenous Staphylococcus aureus meningitis. A 10-year nationwide study of 96 consecutive cases. BMC Infect Dis 2006, 6:49.\u003c/li\u003e\n\u003cli\u003eAguilar J, Urday-Cornejo V, Donabedian S, Perri M, Tibbetts R, Zervos M: Staphylococcus aureus meningitis: case series and literature review. Medicine (Baltimore) 2010, 89(2):117-125.\u003c/li\u003e\n\u003cli\u003eBrouwer MC, Keizerweerd GD, De Gans J, Spanjaard L, Van De Beek D: Community acquired Staphylococcus aureus meningitis in adults. Scand J Infect Dis 2009, 41(5):375-377.\u003c/li\u003e\n\u003cli\u003eLerche A, Rasmussen N, Wandall JH, Bohr VA: Staphylococcus aureus meningitis: a review of 28 consecutive community-acquired cases. Scand J Infect Dis 1995, 27(6):569-573.\u003c/li\u003e\n\u003cli\u003eGordon JJ, Harter DH, Phair JP: Meningitis due to Staphylococcus aureus. Am J Med 1985, 78(6 Pt 1):965-970.\u003c/li\u003e\n\u003cli\u003eChang WN, Lu CH, Wu JJ, Chang HW, Tsai YC, Chen FT, Chien CC: Staphylococcus aureus meningitis in adults: a clinical comparison of infections caused by methicillin-resistant and methicillin-sensitive strains. Infection 2001, 29(5):245-250.\u003c/li\u003e\n\u003cli\u003evan de Beek D, Brouwer MC, Thwaites GE, Tunkel AR: Advances in treatment of bacterial meningitis. Lancet 2012, 380(9854):1693-1702.\u003c/li\u003e\n\u003cli\u003eMcHenry MC, Easley KA, Locker GA: Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis 2002, 34(10):1342-1350.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Background characteristics and causative bacteria of 35 patients with community-acquired bacterial meningitis.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eAge (years), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e62.9 \u0026plusmn; 13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eMale: female ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e21:14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eUniversity Hospital: City Hospital case ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e24: 11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eThe early-period: late-period ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e17:18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eCausative bacteria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus\u003c/em\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003epneumoniae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e11 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e3 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus\u0026nbsp;equisimilis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e3 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eListeria monocytogenes\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus agalactiae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus salivarius\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus sanguinis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eActinomyces species\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e Undefined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e11 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSD, standard deviation.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Concomitant infectious foci in 35 patients with community-acquired bacterial meningitis.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eConcomitant infectious foci\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eSinusitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e7 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eOtitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e3 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eSpondylitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e8 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003e With adjacent soft tissue infection (e.g., psoas abscess)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eEndocarditis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eSinusitis, otitis, and/or pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e11 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eSpondylitis and/or endocarditis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e11 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75.1852%;\"\u003e\n \u003cp\u003eAny infectious foci\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.8148%;\"\u003e\n \u003cp\u003e20 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3. Clinical and laboratory features of 35 patients with community-acquired bacterial meningitis with and without concomitant endocarditis and/or spondylitis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"590\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003ePatients with concomitant endocarditis and/or spondylitis\u003c/p\u003e\n \u003cp\u003e(n = 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003ePatients without\u0026nbsp;\u003c/p\u003e\n \u003cp\u003econcomitant\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eendocarditis and/or spondylitis\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n = 24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eAge (years), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e61.5 \u0026plusmn; 10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e63.6 \u0026plusmn; 15.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e7 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e14 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eUniversity Hospital case, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e8 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e16 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eThe late-period, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e9 (82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e9 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eImmunocompromised state, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Diabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e2 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e6 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e4 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Receiving immunosuppressants or steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e3 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Renal failure and/or hepatic failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e2 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Any of the above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e2 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e11 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eCausative bacteria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e3 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e8 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e3 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003cem\u003eStreptococcus\u0026nbsp;species *\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e3 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e3 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Other bacteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e1 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e3 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Undefined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e1 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e7 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eBlood examination, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e WBC (/\u0026mu;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e13397 \u0026nbsp;\u0026plusmn; 6278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e15670 \u0026plusmn; 9084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e CRP (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e20.4 \u0026plusmn; 9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e14.1 \u0026plusmn; 11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003ePositive blood culture, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e9/11 (82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e10/19 (53)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eCSF examination, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Cell count (/\u0026mu;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e852 \u0026plusmn; 1899\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e7741 \u0026plusmn; 14008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Percentage of neutrophils (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e47.1 \u0026plusmn; 30.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e74.1 \u0026plusmn; 25.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e Protein (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e468 \u0026plusmn; 817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e337 \u0026plusmn; 235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eDuration of antibiotic therapy (days),\u003c/p\u003e\n \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e173\u0026nbsp;\u0026plusmn;\u0026nbsp;211.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e30.5\u0026nbsp;\u0026plusmn;\u0026nbsp;17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eHospitalization length of stay (days),\u003c/p\u003e\n \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e88.9 \u0026plusmn; 40.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e49.9 \u0026plusmn; 33.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003eGlasgow Outcome Scale Score, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e 1 (Death)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e 2 (Vegetable state)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e 3 (Severely disabled)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e4 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e8 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e 4 (Moderately disabled)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e4 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e8 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.6893%;\"\u003e\n \u003cp\u003e 5 (Mild or no disability)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7131%;\"\u003e\n \u003cp\u003e3 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.8829%;\"\u003e\n \u003cp\u003e7 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e*\u0026nbsp;\u003c/sup\u003e\u003cem\u003eStreptococcus equisimilis, Streptococcus agalactiae, Streptococcus salivarius, and Streptococcus sanguinis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCRP, C-reactive protein; CSF, cerebrospinal fluid; NS, not significant; SD, standard deviation; WBC, white blood cell count.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bacterial meningitis, spondylitis, endocarditis","lastPublishedDoi":"10.21203/rs.3.rs-7055324/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7055324/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground.\u003c/h2\u003e\u003cp\u003eCommunity-acquired bacterial meningitis has been linked to concurrent infectious foci in certain cases. However, reports specifically addressing concomitant infectious foci in patients with community-acquired bacterial meningitis, particularly in recent years, remain scarce. Moreover, the distinct characteristics of various types of concomitant infectious foci in bacterial meningitis cases have yet to be fully elucidated.\u003c/p\u003e\u003ch2\u003eMethods.\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective analysis of 35 consecutive patients diagnosed with community-acquired bacterial meningitis. We assessed the presence, distribution, and frequency of concomitant infectious foci, followed by an evaluation of the clinical characteristics of patients with these infections. Patients were categorized into two groups based on the period of onset: the early-period group (2004\u0026ndash;2013) and the late-period group (2014\u0026ndash;2024).\u003c/p\u003e\u003ch2\u003eResults.\u003c/h2\u003e\u003cp\u003eAmong the 35 patients, 20 (57%) presented with concomitant infections. Based on the site of infection, 7 patients (20%) had sinusitis, 4 (11%) had otitis, 3 (9%) had pneumonia, 8 (24%) had spondylitis, and 4 (12%) had endocarditis. The total number of patients with spondylitis and/or endocarditis was 11 (31%). A significantly higher proportion of patients with concomitant spondylitis and/or endocarditis belonged to the late-period group (82%) compared to those without these infections (38%, P\u0026thinsp;=\u0026thinsp;0.026).\u003c/p\u003e\u003ch2\u003eConclusions.\u003c/h2\u003e\u003cp\u003eSpondylitis and endocarditis occur as concomitant infectious foci in community-acquired bacterial meningitis, with higher frequency than previously reported, and their incidence has been progressively increasing in recent years.\u003c/p\u003e","manuscriptTitle":"Concomitant infectious foci in community-acquired bacterial meningitis: the clinical impact of concomitant spondylitis and endocarditis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 07:35:27","doi":"10.21203/rs.3.rs-7055324/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-08T10:04:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-02T04:24:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330353301600641843117039822508536264700","date":"2025-08-07T03:23:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-05T08:36:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81735976407165682904268289710818715459","date":"2025-07-27T20:36:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T06:23:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-10T06:09:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T10:17:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-09T10:16:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-07-06T01:33:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"854d6b65-fae7-435d-a57a-001f17f2ebb3","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:03:58+00:00","versionOfRecord":{"articleIdentity":"rs-7055324","link":"https://doi.org/10.1186/s12879-025-12448-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-12-26 15:58:36","publishedOnDateReadable":"December 26th, 2025"},"versionCreatedAt":"2025-07-18 07:35:27","video":"","vorDoi":"10.1186/s12879-025-12448-3","vorDoiUrl":"https://doi.org/10.1186/s12879-025-12448-3","workflowStages":[]},"version":"v1","identity":"rs-7055324","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7055324","identity":"rs-7055324","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}