Investigating Bacterial Penetration of the Blood-Brain Barrier for the Pathogenesis, Prevention, and Therapy of Bacterial Meningitis.

The most distressing aspect of bacterial meningitis is limited improvement in the mortality and morbidity despite attributable advances in antimicrobial chemotherapy and supportive care. A major contributing factor to such mortality and morbidity is our incomplete understanding of the pathogenesis of this disease. Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules. Determination and characterization of such host and bacterial factors have been instrumental for developing our current knowledge on the pathogenesis of bacterial meningitis. In addition, counteracting such host and microbial factors has been shown to be efficacious in the prevention of bacterial meningitis. Antimicrobial therapy alone has limited efficacy in improving the outcome of bacterial meningitis. Recent studies suggest that counteracting targets contributing to bacterial penetration of the blood-brain barrier are a beneficial therapeutic adjunct to antimicrobial therapy in improving the outcome of bacterial meningitis. Taken together, these findings indicate that the elucidation of host and bacterial factors contributing to microbial penetration of the blood-brain barrier provides a novel strategy for investigating the pathogenesis, prevention, and therapy of bacterial meningitis.

Meningitis de etiología mixta: tuberculosa y bacteriana por germen no identificado / Meningitis of mixed ethiology (tuberculous and unindentified bacteria)

Se presenta un caso de paciente masculino de 54 años de edad, sin inmunosupresión ni evidencia de la misma durante su hospitalización, que consulta por cefalea y signos meníngeos. Se realiza Punción Lumbar (PL) compatible con meningitis bacteriana por lo que se indica tratamiento empírico con mejoría franca de la sintomatología con excepción de la esorientación. Una vez en mejores condiciones se reciben los valores de la ADA los cuales están elevados compatibles con Tuberculosis Meníngea (TBM). Se realiza nueva PL para confirmar dicho valor, lo que se logra y además se demuestra un aumento leve. A los 20 días de la hospitalización, y luego de la mejoría franca, el paciente presenta nuevamente cefalea, fiebre y bradilalia por lo que se inicia tratamiento anti TB con mejoría progresiva de los síntomas. Se presenta el caso y se revisa la literatura(AU)

We present a 54-year-old male patient, with no immunosuppression who consulted for headache and meningeal signs. Lumbar tap (LT) was compatible with bacterial meningitis and empirical treatment was startes with a clear improvement in symptomatology, except for disorientation. Then ADA values were received and its values were francly compatible with Meningeal Tuberculosis (TBM). A new LT was performed to confirm this value, also showeds a slight increase. Twenty days after the hospitalization, and after the frank improvement, the patient again presented again with headache, fever and bradylalia, thus initiating anti-TB treatment with progressive improvement of symptoms. The case is presented and the literature is reviewed(AU)

Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

BACKGROUND: Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. METHODS: Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. RESULTS: Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

Neurobrucellosis with thalamic infarction: a case report.

Brucellosis is prevalent in North and East Africa, the Middle East, South and Central Asia, South and Central America and the Mediterranean countries of Europe. In 5% of cases it may lead to central nervous system manifestation presenting most often as a meningitis or meningoencephalitis. Here we report and discuss a case of neurobrucellosis with meningitis with cranial nerves neuritis. A 56-year-old German male was admitted with bilateral abducens nerve palsy, amblyacousia and intractable headaches. An enzyme-linked immunosorbent assay (ELISA) revealed antibodies against Brucella in serum and cerebrospinal fluid (CSF). Additionally, our patient suffered from an infarction of the left thalamus. In conclusion, in cases of unresponsive meningitis or meningoencephalitis and history of travel in endemic regions, neurobrucellosis should be considered. If initial microbiological tests fail, complementary investigations such as ELISA are indicated to detect Brucella species in serum and/or CSF.

Management of anthrax meningitis.

Meningitis due to infection with Bacillus anthracis is considered an infrequent manifestation of the disease but one associated with high mortality. The bioterrorism event in the USA in the autumn of 2001 demonstrated our need for a better understanding of anthrax meningitis, as well as management and antimicrobial therapy. However, human clinical trials are not possible and animal experiments to guide such therapy are limited. An approach to the treatment of anthrax meningitis, based on the pathogenicity of B anthracis, the pharmacokinetics and pharmacodynamics of individual antimicrobial agents, studies of anthrax post-exposure prophylaxis in non-human primates, experience with antimicrobial susceptibility patterns of the 2001 outbreak strain, and the clinical experience with inhalational anthrax cases during the 2001 outbreak is presented. These outbreak data, the failure of previous single-drug regimens, the concerns of resistance, and the need for coverage for other causes of bacterial mengingitis suggest initial treatment of suspected anthrax meningitis should anchor on an intravenous fluoroquinolone and should include one or two other agents with activity against B anthracis and good penetration into the central nervous system. Such other agents include penicillin, ampicillin, meropenem, vancomycin, and rifampicin.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.