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Background: Sensorineural hearing loss is the most common sequela in survivors of bacterial meningitis (BM). In the past we developed a validated prediction model to identify children at risk for post-meningitis hearing loss. It is known that host genetic variations, besides clinical factors, contribute to severity and outcome of BM. In this study it was determined whether host genetic risk factors improve the predictive abilities of an existing model regarding hearing loss after childhood BM., Methods: Four hundred and seventy-one Dutch Caucasian childhood BM were genotyped for 11 single nucleotide polymorphisms (SNPs) in seven different genes involved in pathogen recognition. Genetic data were added to the original clinical prediction model and performance of new models was compared to the original model by likelihood ratio tests and the area under the curve (AUC) of the receiver operating characteristic curves., Results: Addition of TLR9-1237 SNPs and the combination of TLR2 + 2477 and TLR4 + 896 SNPs improved the clinical prediction model, but not significantly (increase of AUC's from 0.856 to 0.861 and from 0.856 to 0.875 (p = 0.570 and 0.335, respectively). Other SNPs analysed were not linked to hearing loss., Conclusions: Although addition of genetic risk factors did not significantly improve the clinical prediction model for post-meningitis hearing loss, AUC's of the pre-existing model remain high after addition of genetic factors. Future studies should evaluate whether more combinations of SNPs in larger cohorts has an additional value to the existing prediction model for post meningitis hearing loss.

Objective: This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice., Study Design: 116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values., Results: Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort., Conclusions: Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing.

Background: Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis., Methods: We collected data prospectively between October 1998 and April 2002, on 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients >16 years. Patients were dichotomized according to blood glucose level on admission. A cutoff random non-fasting blood glucose level of 7.8 mmol/L (140 mg/dL) was used to define hyperglycemia, and a cutoff random non-fasting blood glucose level of 11.1 mmol/L (200 mg/dL) was used to define severe hyperglycemia. Unfavorable outcome was defined on the Glasgow outcome scale as a score <5. We also evaluated characteristics of patients with a preadmission diagnosis of diabetes mellitus., Results: 69% of patients were hyperglycemic and 25% severely hyperglycemic on admission. Compared with non-hyperglycemic patients, hyperglycemia was related with advanced age (median, 55 yrs vs. 44 yrs, P < 0.0001), preadmission diagnosis of diabetes (9% vs. 3%, P = 0.005), and distant focus of infection (37% vs. 28%, P = 0.02). They were more often admitted in coma (16% vs. 8%; P = 0.004) and with pneumococcal meningitis (55% vs. 42%, P = 0.007). These differences remained significant after exclusion of patients with known diabetes. Hyperglycemia was related with unfavorable outcome in a univariate analysis but this relation did not remain robust in a multivariate analysis. Factors predictive for neurologic compromise were related with higher blood glucose levels, whereas factors predictive for systemic compromise were related with lower blood glucose levels. Only a minority of severely hyperglycemic patients were known diabetics (19%). The vast majority of these known diabetic patients had meningitis due to Streptococcus pneumoniae (67%) or Listeria monocytogenes (13%) and they were at high risk for unfavorable outcome (52%)., Conclusion: The majority of patients with bacterial meningitis have hyperglycemic blood glucose levels on admission. Hyperglycemia can be explained by a physical stress reaction, the central nervous system insult leading to disturbed blood-glucose regulation mechanisms, and preponderance of diabetics for pneumococcal meningitis. Patients with diabetes and bacterial meningitis are at high risk for unfavorable outcome.

We present 9 patients with community acquired Staphylococcus aureus meningitis. Foci of infection outside the central nervous system were present in 8 (89%) patients, mostly endocarditis and pneumonia. Cardiorespiratory complications occurred frequently and 6 patients died (67%). Identification and treatment of the primary focus of infection should be a priority in these patients.

Background: Patients may experience multiple episodes of bacterial meningitis. Information from large studies of recurrent meningitis is limited. We evaluated the incidence of recurrent bacterial meningitis and the distribution of causative organisms in The Netherlands., Methods: Data for patients with bacterial meningitis were prospectively collected nationwide for the period 1988-2005. Recurrent meningitis was defined as an episode of meningitis that either occurred >or=28 days after a previous episode or occurred <28 days after a previous episode but was caused by a different pathogen or different subtype of the same pathogen., Results: Of 18,915 patients, 202 (predominantly male) patients had recurrent bacterial meningitis (P< .01). Prevailing causative organisms were Streptococcus pneumoniae (40% of cases), Neisseria meningitidis (22%), and non-type b Haemophilus influenzae (9%). Pneumococci serotypes included in the heptavalent vaccine caused only 36% of cases of recurrent pneumococcal meningitis. The proportion of episodes caused by meningococcus serogroups W135, Y, and Z was higher among patients with recurrent meningitis than among those with nonrecurrent meningitis (odds ratio, 12.8), and the proportion caused by nontypeable and type f H. influenzae was also higher among patients with recurrent meningitis (odds ratio, 3.8 and 5.6, respectively)., Conclusions: In The Netherlands, the prevalence of recurrent bacterial and fungal meningitis is low. The distribution of causative microorganisms differs between cases of recurrent meningitis and cases of nonrecurrent meningitis; this could be associated with vaccination.

We present four patients with Streptococcus suis meningitis identified during a 3.5-year prospective surveillance study in the Netherlands. All cases were associated with exposure to pigs. Patients presented with classic symptoms and signs of bacterial meningitis. Outcome was characterized by severe hearing loss. Physicians should be aware of occupational exposure with S. suis and risk of meningitis associated with this pathogen.

Objective: To derive and validate a bedside risk score for adverse outcome in adults with bacterial meningitis., Methods: We derived a score for the risk for an unfavorable outcome (Glasgow Outcome Scale score 1-4) by performing logistic regression analyses of data from a prospective cohort study (Dutch Meningitis Cohort; N = 696). A key set of independent prognostic variables was selected from 22 potential predictors. A nomogram based on these key variables was constructed to facilitate use in clinical practice. To validate this nomogram, we used data from our randomized controlled trial on adjunctive dexamethasone therapy in adults with bacterial meningitis (European Dexamethasone Study; N = 301)., Results: Unfavorable outcome occurred in 237 of 696 episodes (34%) in the Dutch Meningitis Cohort; 143 patients (21%) died. In the analysis, 6 of 22 variables that are routinely available within 1 hour after admission were robust enough for inclusion in the final risk score: age, heart rate, Glasgow Coma Scale score, cranial nerve palsies, a cerebrospinal fluid leukocyte count less than 1,000 cells/mm3, and gram-positive cocci in cerebrospinal fluid Gram's stain. The concordance index for the risk score was 0.84 (95% confidence interval, 0.80-0.87) in the original cohort and 0.81 (95% confidence interval, 0.74-0.87) in the external validation cohort (European Dexamethasone Study)., Interpretation: This bedside risk score can be used to identify patients with a high risk for unfavorable outcome in adults with bacterial meningitis within 1 hour after the initial presentation.

Background: Community-acquired recurrent bacterial meningitis in adults is a relatively rare disease. All previous data were derived from small retrospective case series., Methods: We prospectively evaluated episodes of recurrent bacterial meningitis in a nationwide cohort study in The Netherlands., Results: Thirty-four episodes of recurrent bacterial meningitis were identified among 31 patients; 3 patients experienced 2 episodes during the study period. The mean age was 43 years, and 25 (74%) of 34 episodes occurred in men. Predisposing conditions were involved in 26 (77%) of 34 episodes; the most common predisposing conditions were remote head injury (17 [53%] of 32 episodes) and cerebrospinal fluid (CSF) leakage (9 [32%] of 28 episodes). Lumbar puncture revealed an individual CSF indicator of bacterial meningitis for almost all episodes (88%). The outcome was death for 5 (15%) of 34 episodes; 1 additional patient had a suboptimal score on the Glasgow Outcome Scale., Conclusion: We conclude that most patients with recurrent meningitis are male and have predisposing conditions, which, in most cases, are remote head injury or CSF leakage.

We studied the characteristics of strains isolated from neonates with group B streptococci sepsis and meningitis, before and after the introduction of antibiotic prophylaxis in The Netherlands. In 1999, 1 year after this introduction the serotype and genotype distribution and the susceptibility patterns of the GBS strains had not changed. Penicillins remain drugs of first choice to prevent and treat neonatal GBS disease.

Objectives: To describe clinical features of bacterial meningitis in older people., Design: Cohort study., Setting: Hospitals in the Netherlands., Participants: Patients aged over 16 with community-acquired bacterial meningitis, confirmed using cerebrospinal fluid culture., Measurements: Data were collected prospectively. The cohort was dichotomized with respect to age (>or=60 vs 17-59)., Results: Two hundred fifty-seven of 696 episodes of community-acquired bacterial meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults. Older people more often presented with the triad of fever, neck stiffness, and altered mental status than younger adults (58% vs 36%; P<.001). In older people, meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger adults, Neisseria meningitidis was the most common pathogen, responsible for 221 episodes (50%). Elderly patients more often developed complications than younger adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs 13%; P<.001). Older people tended to die more often from cardiorespiratory failure (25% vs 11%; P=.06), whereas younger adults more often died from brain herniation (23% vs 2%; P=.004)., Conclusion: Elderly patients with bacterial meningitis often present with classic symptoms of bacterial meningitis. Bacterial meningitis within this age group is predominantly due to S. pneumoniae and is associated with high morbidity and mortality rates. Whereas older people die frequently of cardiorespiratory failure, younger adults more often die of brain herniation.

Background: Although the coexistence of bacterial meningitis and arthritis has been noted in several studies, it remains unclear how often both conditions occur simultaneously., Methods: We evaluated the presence of arthritis in a prospective nationwide cohort of 696 episodes of community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, which occurred in patients aged >16 years. The diagnosis of arthritis was based upon the judgment of the treating physician. To identify differences between groups Fisher exact statistics and the Mann-Whitney U test were used., Results: Arthritis was recorded in 48 of 696 (7%) episodes of community-acquired bacterial meningitis in adults. Joint-fluid aspirations were performed in 23 of 48 patients (48%) and joint-fluid cultures yielded bacteria in 6 of 23 patients (26%). Arthritis occurred most frequently in patients with meningococcal meningitis (12%). Of the 48 patients with bacterial meningitis and coexisting arthritis, four died (8%) and 10 (23%) had residual joint symptoms., Conclusion: Arthritis is a common manifestation in patients with community-acquired bacterial meningitis. Functional outcome of arthritis in bacterial meningitis is generally good because meningococcal arthritis is usually immune-mediated, and pneumococcal arthritis is generally less deforming than staphylococcal arthritis. Nevertheless, additional therapeutic measures should be considered if clinical course is complicated by arthritis. In patients with infectious arthritis prolonged antibiotic therapy is mandatory.

Background: We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis., Methods: From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis., Results: We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count., Conclusions: In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae., (Copyright 2004 Massachusetts Medical Society.)

In The Netherlands, national guidelines for the treatment of adult patients with bacterial meningitis were introduced in October 1997. In 1998 we began a prospective, nationwide study to evaluate the compliance with these consensus-based guidelines. In addition, we evaluated whether the recommended initial treatment provides adequate microbiological coverage. From October 1998 to January 2000, 365 adults with bacterial meningitis were identified using information from The Netherlands Reference Laboratory for Bacterial Meningitis; 263 patients were classified into four categories depending on patient's age and underlying health status. In the first category, patients 16-60 years without risk factors, Neisseria meningitidis was the most common pathogen (53%); 62 of 127 patients (49%) received treatment in compliance with the guidelines. In the second and third categories, patients >60 years without risk factors and those with risk factors independently of age, Streptococcus pneumoniae caused 61% and 58% of cases, respectively. Compliance in these categories was about 17%. Overall, 33% of patients received treatment in compliance with the guidelines. The microbiological coverage of patients treated in compliance and not in compliance with the guidelines was 98% and 93%, respectively. In conclusion, 1 year after national consensus-based guidelines for the initial treatment of adult patient with bacterial meningitis were introduced in The Netherlands, only one-third of Dutch physicians were adhering to the guidelines. The microbiological coverage for the patients who were treated in compliance with the guidelines was almost complete (98%).

Seventy cerebrospinal fluid Escherichia coli isolates from infants with neonatal bacterial meningitis (NBM), as submitted to the Netherlands Reference Laboratory for Bacterial Meningitis from 1989 through 1997, were assessed for phylogenetic background and extended virulence genotypes, in comparison with the E. coli reference collection, by using molecular methods. Phylogenetic group B2 significantly predominated overall (81%). The 4 major phylogenetic clusters exhibited distinctive virulence genotypes, suggesting diverse evolutionary histories for the individual genes. Many genes not previously studied in NBM, notably diarrhea-associated cdtB (cytolethal distending toxin [46%]) and urinary tract infection-associated ompT (outer membrane protease T [96%]), were as or more prevalent than traditional NBM-associated traits, such as ibeA (invasion of brain endothelium [33%]), sfaS (S fimbriae [59%]), and K1 capsule (81%). These findings provide novel insights into the phylogenetic origins of NBM-associated E. coli and suggest numerous new potential targets for preventive interventions against this dire disease.