Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis.

Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 10(7) CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h. Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNF alpha antibodies given IC with 20 ng Hib LOS or 2 X 10(6) CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.

Bacterial meningitis: epidemiology, pathogenesis and management update.

Bacterial meningitis continues to be an important disease throughout the world and can be a life-threatening emergency if not suspected, appropriately diagnosed and managed expeditiously. The epidemiology of bacterial meningitis has changed dramatically over the last 20 years, primarily as a result of the introduction of conjugate vaccines against the common meningeal pathogens, such that in the developed world where vaccination is routinely utilized, bacterial meningitis has become a disease of adults rather than of infants and children. The management approach to patients with suspected or proven bacterial meningitis includes emergent cerebrospinal fluid analysis and initiation of appropriate antimicrobial and adjunctive therapies. The choice of empirical antimicrobial therapy is based on the patient's age and underlying disease status; once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Many patients with suspected or proven bacterial meningitis should also receive adjunctive dexamethasone therapy. This is based on experimental animal model data which demonstrated that the subarachnoid space inflammatory response that results from antimicrobial-induced bacterial lysis can contribute to morbidity and mortality. Clinical studies have demonstrated the benefit of adjunctive dexamethasone in infants and children with Haemophilus influenzae type B meningitis, and adults with pneumococcal meningitis, in which mortality and adverse outcome are reduced. Use of adjunctive dexamethasone in adults with meningitis caused by other bacteria, and in infants and children with pneumococcal meningitis, is controversial. To be effective, adjunctive dexamethasone should be administered concomitant with or just prior to the first antimicrobial dose for maximal effect on the subarachnoid space inflammatory response.