Morphology of pneumococcal meningitis in adults

Morphologically, acute pneumococcal meningitis runs like meningoencephalitis. A major part of pneumococcal meningitides belongs to primary ones. Liquor bacterioscopy using Gram's smear staining is an early method for their diagnosis.     

Hearing loss in adults surviving pneumococcal meningitis is associated with otitis and pneumococcal serotype

We assessed the incidence of hearing loss and its relationship with clinical characteristics and pneumococcal serotypes in adults surviving pneumococcal meningitis. We analysed hearing loss in 531 adults surviving pneumococcal meningitis included in two prospective nationwide cohort studies performed from April 1998 through to October 2002 and March 2006 through to January 2009. Hearing loss was evaluated on admission and discharge for all patients. Severe hearing loss was assessed by pure tone average on audiology and corrected for age, or by the combination of hearing loss on discharge and a score on the Glasgow Outcome Scale below 5, which could not be explained by other neurological sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal outcome were included. Predisposing conditions for pneumococcal meningitis were present in the majority of patients (64%), most commonly otitis (36%). Hearing loss was present at discharge in 116 patients (22%) and was classified as mild in 53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.66-4.02; p < 0.001) and inversely related to serotype 23 F infection (OR, 0.36; 95% CI, 0.13-0.98; p = 0.025), but not with parameters of disease severity or indicators of cerebrospinal fluid inflammation severity. Meningitis due to pneumococcal serotype 3 was associated with the highest rate of hearing loss. Hearing loss frequently complicates pneumococcal meningitis. Risk factors for hearing loss were infection with pneumococcal serotype 23 F and otitis, but not disease severity. Otitis and resulting perilympathic inflammation contribute to meningitis-associated hearing loss.     

Dexamethasone treatment in adults with pneumococcal meningitis: risk factors for death

In experimental meningitis, adjunctive treatment with steroids reduces cerebrospinal fluid inflammation and thereby improves neurological outcome. On the basis of these findings, several clinical trials have assessed treatment with adjunctive steroids in bacterial meningitis, with conflicting results. Recently, the results of the European Dexamethasone Study showed a beneficial effect of adjunctive dexamethasone in adults with bacterial meningitis. In that study, the effect of dexamethasone on outcome was most striking in patients with pneumococcal meningitis. The aim of the present study was to further evaluate the effect of dexamethasone in adults with pneumococcal meningitis by performing a post hoc analysis of the European Dexamethasone Study. In a multivariate analysis, tachycardia (p=0.02), advanced age (p=0.03), low score on the Glasgow Coma Scale (p=0.03), positive blood culture (p=0.04), and absence of dexamethasone therapy (p=0.05) were independent predictors for death. Patients who were treated with adjunctive dexamethasone were less likely to develop both systemic and neurological complications during hospitalisation, compared with patients who received placebo. In conclusion, independent risk factors for death in pneumococcal meningitis are tachycardia, advanced age, low level of consciousness, bacteraemia, and absence of dexamethasone therapy. Treatment with adjunctive dexamethasone in adults with pneumococcal meningitis reduces both systemic and neurological complications.     

Clinical features and prognostic factors in childhood pneumococcal meningitis.

BACKGROUND AND PURPOSE: Despite progress in antibiotic therapy and intensive care, childhood pneumococcal meningitis remains a devastating disease, with morbidity and mortality rates among the highest of any cause of bacterial meningitis. We conducted this study to find the factors associated with disease outcome in clinical settings. METHODS: All pediatric medical charts during the period from January 1984 to December 2003 with the diagnosis of pneumococcal meningitis were reviewed. We recorded patients' symptoms and signs, laboratory data and treatments. Outcome and neurological complications were also analyzed. RESULTS: In total, 40 episodes of pneumococcal meningitis from 37 patients aged 3 months to 10 years were identified. Predisposing factors were found in 13 patients (35.1%), and included recent history of head injury, immunocompromised states and cranial base anomaly. All patients had fever during illness. Patients older than 24 months of age tended to complain of nuchal rigidity (19/21, 90.5%) and those younger than 6 months of age tended to present irritability (6/7, 85.7%). The overall mortality rate was 25% (10 out of 40 episodes). The following variables were associated with mortality after statistical analysis: consciousness disturbance, shock, endotracheal tube intubation and hyponatremia (sodium <130 mEq/L) at admission (p=0.001, p<0.001, p<0.001, and p=0.012, respectively). Also, laboratory findings of less than 20/mm3 white cell count in cerebrospinal fluid (CSF), lower CSF glucose level and CSF-to-blood glucose ratio were significantly higher in non-survivors (p=0.003, p=0.009, p=0.027). Variables associated with morbidity were seizure attack and focal neurological sign occurring hospitalization (p=0.017, p=0.017). CONCLUSIONS: The mortality of childhood pneumococcal meningitis remains high. If a child with pneumococcal meningitis presents with consciousness disturbance, hypotension, endotracheal intubation or hyponatremia at admission, the disease mortality rate increases. CSF findings with low white cell count, low glucose level and CSF-to-blood glucose ratio are also warning signs of a bad outcome. Seizure attack and focal neurological sign are the factors associated with further neurological sequelae.     

Diagnosis of pneumococcal meningitis

Acute pneumococcal meningitis runs the course of meningoencephalitis morphologically, and when the incidence of meningococcal meningitis is on the increase, this disease may well be mistaken for pneumococcal meningitis (two case reports of such misdiagnosis are presented) or stroke (one case is reported). An effective method for recognizing pneumococcal meningitis at an early stage is bacterioscopic examination of Gram-stained cerebrospinal-fluid smears.     

Long-term neurologic and cognitive outcome and quality of life in adults after pneumococcal meningitis

ObjectivesTo perform a cross-sectional cohort study on long-term neurologic, cognitive and quality-of-life outcome in adults surviving pneumococcal meningitis.MethodsAdult survivors of community-acquired pneumococcal meningitis from a Dutch nationwide prospective cohort study were evaluated 1 to 5 years after acute illness. The control group consisted of partners or proxies of patients. Neurologic examination was performed and cognitive domains were tested with the Vienna Test System Cognitive Basic Assessment Test set (VTS COGBAT). The Research and Development (RAND)-36 and adapted Cognitive and Emotional Consequences of Stroke (CLCE)-24 questionnaires assessed perceived cognitive functioning and quality of life. Differences between group scores were tested with multivariate analyses of variance.ResultsA total of 80 pneumococcal meningitis patients and 69 controls were evaluated. After a median of 2 years (interquartile range, 2–3) after acute illness, 27 (34%) of 79 patients had persistent neurologic sequelae, most commonly hearing loss (21/79, 27%). On overall neuropsychologic evaluation, patients performed worse than the controls (MANCOVA; p 0.008), with alertness (z score −0.33, p 0.011) and cognitive flexibility (z score −0.33, p 0.027) as the most affected domains. Cognitive impairment was present in 11 (14%) of 79 patients. CLCE-24 questionnaires revealed cognitive impairment on all domains, most commonly for cognitive speed (53/75, 71%), attention (45/75, 60%) and memory (46/75, 61%). Patients had lower quality-of-life scores than controls (item physical functioning, (median) patients vs. controls, 80 vs. 95, p < 0.001; social functioning, (median) 81 vs. 100, p 0.003; perceived health, (mean) 59 vs. 70, p 0.005), which correlated with cognitive complaints (R = 0.66, p < 0.001).ConclusionsAdults after pneumococcal meningitis are at high risk of long-term neurologic and neuropsychologic deficits impairing daily life activities and quality of life.     

Pathogenesis and pathophysiology of pneumococcal meningitis

Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.     

Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid,Spain

European Journal of Clinical Microbiology & Infectious Diseases - The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for...     

Molecular epidemiological characteristics of pneumococcal meningitis in children

The molecular epidemiological characteristics of pneumococcal meningitis in children were studied. Pneumococcal isolates were characterized by serotyping and two genotyping methods, BOX fingerprinting and restriction fragment end labeling, to evaluate whether clonal strains were present within the serotypes or serogroups. During a 17-year period, 68 children admitted to the Sophia Children's Hospital were diagnosed with meningitis due toStreptococcus pneumoniae. Pneumococcal isolates from 44 patients were still available for analysis. All strains were susceptible to penicillin. Serotypes/ serogroups 14,19, 6, and 18 represented 56% of all isolates. The results of the molecular typing methods demonstrate the absence of clonal relatedness between isolates from patients with pneumococcal meningitis.     

Histochemical demonstration of neuraminidase effects in pneumococcal meningitis

In three cases of pneumococcal meningitis the in vivo action of pneumococcal neuraminidase could be demonstrated. The removal of sialic acid was demonstrated in necrospy material by the use of labeled peanut agglutinin, which has a high specific affinity for the subterminal disaccharide beta-D-galactopyranosyl-(1-3)N-acetyl-D-galactosamine, thereby exposed. Furthermore, this lectin was used for a rapid in vitro histochemical assay of neuraminidase activity in cerebrospinal fluid and culture medium taken from these cases. From the clinical point of view the exposure of the disaccharide which represents the immunodominant group of the Thomsen-Friedenreich antigen may induce immunologic reactions, because all human sera contain antibodies to this cryptic antigen. Thereby, neuraminidase can contribute to the poor prognosis of pneumococcal meningitis.     

Establishment of rat pneumococcal meningitis models: a histopathological analysis

The aim of this study was to perform a preliminary investigation of the pathogenesis of bacterial meningitis-induced brain injury by establishing rat pneumococcal meningitis models. Infant Wistar rats were intracranially inoculated with different concentrations of Streptococcus pneumoniae. Rats were sacrificed at different time points to observe clinical symptoms and pathological changes in brain tissues. Twenty-four hours after intracranial inoculation with Streptococcus pneumoniae, regardless of high or low concentrations of bacterial inoculation, all rats developed bacterial meningitis with manifestations such as lethargy and seizures. Pathological changes in brain tissues included subarachnoid and intraventricular inflammation, vasodilation and vascular congestion, and cortical neuronal necrosis. The number of rats with seizures, the degree of cerebral vascular disease, and the extent of neuronal damage were associated with the concentration of bacterial inoculum. Thirty days after infection, brain tissue weight significantly reduced. The pathological changes induced by inoculation with pneumococcal meningitis in Wistar rats were similar to those seen in the human brain. The possible mechanisms of brain damage caused by meningitis are cerebrovascular inflammation and disruption of regional cerebral blood flow.