Otitis in patients with Community-Acquired Bacterial Meningitis: A Nationwide Prospective Cohort Study.

BACKGROUND: Otitis is commonly associated with community-acquired bacterial meningitis but role of ear surgery as treatment is debated. In this study, we investigated the impact of otitis and ear surgery on outcome of adults with community-acquired bacterial meningitis. METHODS: We analyzed episodes of adults with community-acquired bacterial meningitis from a nationwide prospective cohort study in the Netherlands, between March 2006 to July 2021. RESULTS: A total of 2,548 episodes of community-acquired bacterial meningitis were evaluated. Otitis was present in 696 episodes (27%). In these patients the primary causative pathogen was Streptococcus pneumoniae (615 of 696 [88%]), followed by Streptococcus pyogenes (5%) and Haemophilus influenzae (4%). In 519 of 632 otitis episodes (82%) an ear-nose-throat specialist was consulted, and surgery was performed in 287 of 519 (55%). The types of surgery performed were myringotomy with ventilation tube insertion in 110 of 287 episodes (38%), mastoidectomy in 103 of 287 (36%) and myringotomy alone in 74 of 287 (26%). Unfavorable outcome occurred in 210 of 696 episodes (30%) and in 65 of 696 episodes was fatal (9%). Otitis was associated with a favorable outcome in a multivariable analysis (odds ratio 0.74; 95% CI 0.59-0.92; p =0.008). There was no association between outcome and ear surgery. CONCLUSIONS: Otitis is a common focus of infection in community-acquired bacterial meningitis in adults, with S. pneumoniae being the most common causative pathogen. Presence of otitis is associated with a favorable outcome. Ear surgery's impact on the outcome of otogenic meningitis patients remains uncertain.

Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study.

OBJECTIVES: The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. METHODS: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). RESULTS: Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51-68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103-1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9-105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0-2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6-2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4-3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6-3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6-3.9; p < 0.001). DISCUSSION: High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.

Characteristics and prognostic factors of bacterial meningitis in the intensive care unit: a prospective nationwide cohort study.

BACKGROUND: Patients with bacterial meningitis can be severely ill necessitating intensive care unit (ICU) treatment. Here, we describe clinical features and prognostic factors of adults with bacterial meningitis admitted to the ICU in a nationwide prospective cohort study. METHODS: We prospectively assessed clinical features and outcome of adults (age > 16 years) with community-acquired bacterial meningitis included in the MeninGene study between March 1, 2006 and July 1, 2022, that were initially admitted to the ICU. We identified independent predictors for initial ICU admission and for unfavourable outcome (Glasgow Outcome Scale score between 1-4) by multivariable logistic regression. RESULTS: A total of 2709 episodes of bacterial meningitis were included, of which 1369 (51%) were initially admitted to the ICU. We observed a decrease in proportion of patients being admitted to the ICU during the Covid-19 pandemic in 2020 (decreased to 39%, p = 0.004). Median age of the 1369 patients initially admitted to the ICU was 61 years (IQR 49-69), and the rates of unfavourable outcome (47%) and mortality (22%) were high. During the Covid-19 pandemic, we observed a trend towards an increase in unfavourable outcome. Prognostic factors predictive for initial ICU admission were younger age, immunocompromised state, male sex, factors associated with pneumococcal meningitis, and those indicative of systemic compromise. Independent predictors for unfavourable outcome in the initial ICU cohort were advanced age, admittance to an academic hospital, cranial nerve palsies or seizures on admission, low leukocyte count in blood, high C-reactive protein in blood, low CSF: blood glucose ratio, listerial meningitis, need for mechanical ventilation, circulatory shock and persistent fever. 204 of 1340 episodes (15%) that were initially not admitted to the ICU were secondarily transferred to the ICU. The rates of unfavourable outcome (66%) and mortality (30%) in this group were high. CONCLUSIONS: The majority of patients with community-acquired bacterial meningitis are admitted to the ICU, and the unfavourable outcome and mortality rates of these patients remain high. Patients that are initially admitted to non-ICU wards but secondarily transferred to the ICU also had very high rates of unfavourable outcome.

Epidemiology, clinical features and outcome of adults with meningococcal meningitis: a 15-year prospective nationwide cohort study.

Background: We describe the epidemiology, clinical features and outcome of adult meningococcal meningitis in the Netherlands over a 15-year period. Methods: We studied adults (age ≥ 16 years) who were listed by the Netherlands Reference Laboratory for Bacterial Meningitis and/or included in the prospective nationwide cohort study (MeninGene) between January 2006 and July 2021. Incidences were calculated per epidemiological year (July-June). Findings: We identified 442 episodes of adult meningococcal meningitis. The median patient age was 32 years (IQR 18-55) and 226 episodes (51%) occurred in female patients. The annual incidence per 100,000 adults fluctuated, from 0.33 in 2006-2007 to 0.05 in 2020-2021, with a temporal increase up to 0.30 from 2016 to 2018, driven by an outbreak of serogroup W (MenW). Of 442 episodes, 274 episodes (62%) in 273 patients were included in the clinical cohort study. The overall case fatality rate was 4% (10 of 274) and 16% (43 of 274) had an unfavourable outcome (Glasgow Outcome Scale score 1-4). Compared to other serogroups, MenW was associated with higher rates of unfavourable outcome (6 of 16 [38%] vs. 37 of 251 [15%], P = 0.03) and death (4 of 16 [25%] vs. 6 of 251 [2%], P = 0.001). Interpretation: The overall incidence of adult meningococcal meningitis in the Netherlands is low and outcome is generally favourable. An increase of MenW meningitis occurred from 2016 to 2018, which was associated with more unfavourable outcome and death. Funding: Netherlands Organisation for Health Research and Development, European Research Council, National Institute of Public Health and Environmental protection.

Community-acquired Staphylococcus aureus meningitis in adults.

BACKGROUND: Staphylococcus aureus is an uncommon cause of community-acquired bacterial meningitis. We aimed to describe patients with this disease. METHODS: We evaluated clinical characteristics and outcome of adults with community-acquired S. aureus meningitis from prospective nationwide cohort studies from Denmark (2015-2020) and the Netherlands (2006-2021). Whole genome sequencing of S. aureus isolates was performed to evaluate the potential association between clonal complex and clinical characteristics. RESULTS: We evaluated 111 episodes of community-acquired S. aureus meningitis: 65 from Denmark and 46 from the Netherlands. The median age was 66 years (interquartile range [IQR] 50-74) and 43 of 111 patients were female (39%). Concomitant infectious foci were found in 95 of 107 patients (89%), most commonly endocarditis (53 of 109 [49%]) and spondylodiscitis (43 of 109 [39%]). The triad of neck stiffness, altered mental status (Glasgow Coma Scale score <14), and fever was present in only 18 of 108 patients (17%). Surgery was performed in 14 of 33 patients (42%) with spondylodiscitis and 26 of 52 (50%) with endocarditis. A favorable outcome (Glasgow Outcome Scale score 5) occurred in 26 of 111 patients (23%), while 39 (35%) died. The most common bacterial clonal complexes (CC) were CC30 (16 [17%]), CC45 (16 [17%]), CC5 (12 [13%], and CC15 (10 [11%]); no associations between CCs and concomitant foci or outcome were found. CONCLUSIONS: Community-acquired S. aureus meningitis is a severe disease with a high case fatality rate, occurring mainly in patients with concomitant endocarditis or spondylodiscitis.

A risk score for identifying patients at a low risk of bacterial meningitis amongst adults with cerebrospinal fluid leucocytosis and a negative gram stain result: a derivation and validation study.

OBJECTIVES: We aimed to derive and validate a risk score to differentiate patients with bacterial meningitis from those with viral meningitis or encephalitis amongst patients presenting with cerebrospinal fluid (CSF) leucocytosis and a negative Gram staining result. METHODS: We included adults with bacterial and viral meningitis or encephalitis presenting with CSF leukocyte counts of >10 per mm3 and a negative Gram staining result from cohorts in Houston, Texas (2004-2019), and the Netherlands (2012-2021). Derivation and the first validation were performed in the American patients and further validation in the Dutch patients. RESULTS: Derivation was performed in 109 American patients with bacterial meningitis (median age, 56 years; interquartile range [IQR], 46-66 years; 46% women) and 194 with viral meningitis or encephalitis (median age, 46 years; IQR, 33-60 years; 53% women). Serum leukocyte counts of >10.0 × 109/L, CSF leukocyte counts of >2000 per mm3, granulocyte counts of >1180 per mm3, protein levels of >2.2 g/L, glucose levels of <1.9 mmol/L and fever on admission were included in the risk score, which was dichotomized into 'low risk' (0 present) and 'high risk' (>0 present). The first validation showed a sensitivity of 100% (95% CI, 96.6-100) and specificity of 34.0% (95% CI, 27.4-41.2). Further validation in 262 Dutch patients with bacterial meningitis (median age, 57 years; IQR 44-70 years; 45% women) and 68 with viral meningitis (median age, 34 years; IQR, 28-45 years; 60% women) showed a sensitivity of 99.6% (95% CI, 97.9-100) and specificity of 41.2% (95% CI, 29.4-53.7). CONCLUSIONS: Our risk score may be able to rule out bacterial meningitis amongst patients presenting with CSF leucocytosis and a negative Gram staining result. However, it needs prospective testing prior to clinical implementation.

Bacterial meningitis presenting with a normal cerebrospinal fluid leukocyte count.

OBJECTIVES: We describe clinical characteristics and outcome of adults with bacterial meningitis presenting with a normal CSF leukocyte count. METHODS: We studied community-acquired bacterial meningitis with a normal CSF leukocyte count (≤ 5 per mm3) in adults from a prospective nationwide cohort study. RESULTS: From 2006 through 2020, 39 of 2,357 (2%) episodes presented with a normal CSF leukocyte count. Immunocompromising conditions were present in 19 of 39 patients (49%), compared to 690 of 2303 (30%) in patients with elevated leukocytes (P = 0.02). The triad of fever, neck stiffness, and altered consciousness was present in 6 of 34 patients (18%). CSF protein was abnormal in 25 of 37 patients (68%). We identified 3 clinical subgroups: those with severe pneumococcal meningitis (20 patients [51%]), with mainly sepsis (8 [21%]), and a miscellaneous group (11 [28%]). All patients with severe pneumococcal meningitis presented with high CSF protein levels and 18 of 19 (95%) had bacteria in the CSF Gram stain. Outcome was unfavorable in 23 of 39 (59%) patients and 12 (31%) died. CONCLUSION: Patients with bacterial meningitis may present with normal CSF leukocyte counts. In these patients, CSF protein levels and Gram staining are important diagnostic parameters.

Community-acquired bacterial meningitis in patients of 80 years and older.

BACKGROUND: Advanced age is a risk factor for unfavorable outcome in community-acquired bacterial meningitis, but clinical characteristics and outcome in meningitis patients of 80 years or older have not been defined. METHODS: We compared clinical characteristics and outcome of community-acquired bacterial meningitis patients aged 80 years or older and adults under 80 years old within a prospective nationwide cohort study. RESULTS: Out of 2140 episodes identified between March 2006 and July 2018, 149 occurred in patients aged 80 years or older (7%). Common predisposing factors other than age were diabetes mellitus (25 of 148 [17%]), otitis or sinusitis (30 of 136 [22%]), and pneumonia (23 of 141 [16%]). The triad of fever, neck stiffness and altered consciousness was present in 60 of 139 (43%). The most common causative pathogen was Streptococcus pneumoniae (99 of 149 [66%]). Atypical causative pathogens, such as Listeria monocytogenes, Staphylococcus aureus, and Escherichia coli, occurred more often compared to younger patients (49 of 149 [33%] vs 362 of 1991 [18%]; p < 0.001). Patients of 80 years and older had high case fatality rate (75 of 149 [50%]), but 45 of 149 (30%) had a favorable outcome. Characteristics associated with an unfavorable outcome were absence of otitis or sinusitis, presence of aphasia, mono- or hemiparesis, a lower score on the Glasgow Coma Scale, a higher heart rate, a higher blood C-reactive protein concentration and CSF leukocytes <100 per mm3 . CONCLUSIONS: Bacterial meningitis in patients of 80 years of older is associated with high rates of unfavorable outcome and death. Atypical causative pathogens such as L. monocytogenes, S. aureus, and E. coli occur commonly and should be considered when starting empirical antimicrobial therapy in this age group.

CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis.

BACKGROUND AND OBJECTIVES: Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis. METHODS: We measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses. We identified independent predictors of an unfavorable outcome (Glasgow Outcome Scale scores 1-4) by logistic regression. RESULTS: CSF NfL concentrations were evaluated in 429 episodes of 425 patients with community-acquired bacterial meningitis. The median age of 429 episodes was 62 years (interquartile range, 50-69 years). Of note, 290 of 422 (68%) episodes presented with an altered mental status (Glasgow Coma Scale score < 14). Most common causative pathogens were Streptococcus pneumoniae (73%), Neisseria meningitidis (7%), and Listeria monocytogenes (5%). The overall case fatality rate was 62 of 429 (15%), and unfavorable outcome occurred in 57 (37%) of 429 episodes. In multivariate analysis, predictors of unfavorable outcome were older age (OR 1.03, 95% CI 1.01-1.05), cranial nerve palsy (OR 4, 95% CI 1.6-10.3), high serum C-reactive protein concentration (OR 1.3, 95% CI 1.01-1.05), and high CSF NfL concentration (OR 1.5, 95% CI 1.07-2.00). CSF NfL concentrations were higher in patients presenting with focal cerebral deficits (717 pg/mL [416-1,401] vs 412 pg/mL [278-731]; p < 0.001). The area under the curve (AUC) for predicting unfavorable outcome in bacterial meningitis of CSF NfL concentration was 0.69 (95% CI, 0.64-0.74). DISCUSSION: CSF NfL concentration is independently associated with unfavorable outcome in adults with community-acquired bacterial meningitis, suggesting that CSF NfL concentration may be a useful biomarker for prognostic assessment in bacterial meningitis. CLASSIFICATION OF EVIDENCE: Can the level of NfL in CSF (the index test) predict unfavorable outcome in patients with bacterial meningitis, in a cohort of bacterial meningitis patients with a favorable and unfavorable outcome? This study provides Class II evidence that NfL level in CSF is a moderate predictor, with the AUC for predicting unfavorable outcome in bacterial meningitis being 0.69 (95% CI, 0.64-0.74).

SSEP amplitudes add information for prognostication in postanoxic coma.

OBJECTIVE: To investigate whether somatosensory evoked potential (SSEP) amplitude adds information for prediction of poor outcome in postanoxic coma. METHODS: In this retrospective cohort study we included adult patients admitted after cardiac arrest between January 2010 and June 2018 who remained in coma and had SSEP recorded for prognostication. Outcome was dichotomized in poor (Cerebral Performance Category (CPC) 4-5) and good (CPC 1-3) at ICU discharge. Sensitivity of bilaterally absent N20 potential was calculated. In case the N20 potential was not bilaterally absent, the amplitude contralateral to stimulation side (baseline-N20, N20-P25, and maximum) was determined. At a specificity of 100%, SEPP amplitude sensitivities were determined for poor outcome. RESULTS: SSEP recordings were performed in 197 patients of whom 57 had bilaterally absent N20 potentials. From 140 patients, 16 (11%) had a good outcome. The sensitivity for poor outcome of bilaterally absent N20 was 31%. At a specificity of 100%, contralateral amplitude thresholds were 0.34 µV (baseline-N20), 0.99 µV (N20-P25) and 1.0 µV (maximum), corresponding to a sensitivity for poor outcome of 38%, 44% and 40%. Combination of bilaterally absent N20 and a N20-P25 threshold below 0.99 µV yielded a sensitivity of 62%. CONCLUSIONS: Our results confirm that very low cortical SSEP amplitudes are highly predictive of poor outcome in patients with postanoxic coma. Adding 'N20-P25 threshold amplitude' to the 'bilaterally absent N20' criterion, increased sensitivity substantially.