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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of adjunct anti-inflammatory therapy of bacterial meningitis is the containment of heightened inflammation caused by lysis of bacteria by antibiotics. This can be modelled by giving two consecutive intra-cisternal injections of lipopolysaccharide (LPS) to rabbits, the first at 0 h to induce inflammation to mimic that occurring during the proliferation of bacteria in the cerebrospinal fluid (CSF), and the second at 6 h to mimic inflammation subsequent to antibiotic-induced bacterial lysis. Injection of 2.5 ng of LPS induced pleocytosis at 4 h which was preceded by a peak of tumour necrosis factor (TNF) activity at 2 h. A subsequent injection of 25 ng of LPS at 6 h induced second peaks of pleocytosis and CSF TNF. Dexamethasone (1.5 mg/kg, i.v.) administered 15 min or 1 h before the second injection of LPS tended only to reduce CSF TNF, but effectively prohibited further pleocytosis. Brain TNF alpha mRNA levels were unchanged at 6 and 7 h after LPS injection, and were unaffected by dexamethasone. These results indicate that the subarachnoid space is distinct from the general circulation in that the TNF-producing cells present do not display a hypo-responsive state towards LPS as occurs when LPS is injected systemically. Furthermore, dexamethasone is able to attenuate the secondary inflammatory response resulting from a second LPS injection without eliminating a second peak of TNF activity.
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PMID:Dexamethasone treatment of lipopolysaccharide-induced meningitis in rabbits that mimics magnification of inflammation following antibiotic therapy. 760 53

Hearing impairment as a sequela of acute bacterial meningitis is a well known complication. Dexamethasone therapy in addition to antibiotics is beneficial in the reduction of deafness, implicating that inflammation may be one reason for hearing impairment. The risk of hearing impairment in different types of bacterial meningitis is well studied. In very young children < 1.5 years of life the incidence of hearing loss and the possible correlation of laboratory data with the development of deafness is yet unknown. We therefore examined the brainstem auditory evoked potentials in 25 children between the first month and the 16th month of life who we treated for meningitis during 3 years in our hospital. 11 children were treated with dexamethasone. In 9 children we found abnormal brainstem auditory evoked potentials, which we controlled every 3 months. 7 children had transient conductive hearing impairment with good recovery during the first year after the disease. In 2 cases we found permanent bilateral sensorineural hearing loss. There was a significant relationship between hearing loss and elastase in cerebrospinal fluid. Dexamethasone reduced this relationship. A screening of hearing should be performed as routine control in all patients with acute meningitis. The association of high elastase in cerebrospinal fluid and later hearing impairment indicates a pathophysiological relation between activation of granulocytes and hearing loss.
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PMID:[Hearing disorders in children less than 16 months of age after bacterial meningitis with reference to cerebrospinal fluid elastase]. 788 11

Third generation cephalosporin as cefotaxime or ceftriaxone is the best first line treatment. Duration of treatment is 7 to 10 days in uncomplicated disease. Dexamethasone used very early--before or at the same time of the antibiotic injection--seems to decrease sensorial sequelae. Amikacin by IV route, decreases short term complications. For bacterial meningitis due to intermediate penicillin pneumococci, an increase in daily dose of beta-lactamin is recommended; for resistant pneumococci, vancomycin by continuous infusion and with large doses is used. Chemoprophylaxis by rifampicine is effective for both Meningococcus and Haemophilus. Haemophilus influenzae b vaccination will decrease systemic infection due to this pathogen. In newborns, morbidity is higher, due in part to brain abscesses. Therapeutic choice is not the same for materno-foetal and postnatal infection. Antibiotherapy duration is, at least, 15 days and 21 days for gram-negative bacteria.
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PMID:[Treatment of bacterial meningitis in newborn infants and children]. 798 14

Routine use of steroids as adjunctive treatment of bacterial meningitis remains controversial. We have carried out a prospective, placebo-controlled, double-blind study of dexamethasone in 115 children with acute bacterial meningitis in Switzerland. The patients were randomly assigned to receive either placebo (n = 55) or dexamethasone (n = 60) in addition to optimum antibiotic treatment (100 mg/kg daily ceftriaxone). Dexamethasone therapy (0.4 mg/kg) was started 10 min before the first dose of ceftriaxone and given every 12 h for 2 days. Baseline demographic, clinical, and laboratory features of the two groups were similar. After 24 h treatment meningeal inflammation as shown by cerebrospinal fluid (CSF) glucose concentration was significantly less with dexamethasone than with placebo (mean increase in glucose 63 [76] vs 40 [75]%, p = 0.008). However, other indices of inflammation showed similar changes in both groups. Addition of dexamethasone did not affect the rate at which CSF became sterile. Both groups showed prompt clinical responses and similar frequencies of complications (15 vs 12%). Monitoring for possible adverse effects of dexamethasone revealed no abnormalities. At follow-up examinations 3, 9, and 15 months after hospital discharge, 9 (16%) of 55 placebo recipients and 3 (5%) of 60 dexamethasone recipients had one or more neurological or audiological sequelae (p = 0.066); the relative risk of sequelae was 3.27 (95% CI 0.93-11.47). Our results and those of similarly designed studies lead us to believe that adjunctive dexamethasone therapy improves outcome from bacterial meningitis in infants and children. We recommend its use, preferably in the dose regimen used in this study.
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PMID:Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group. 810 28

With improved understanding of the pathophysiology of bacterial meningitis, a number of points in the deleterious inflammatory cascade have been identified as possible sites for modulation. Dexamethasone attenuates tissue injury by inhibiting host mediators at several steps in the inflammatory process. Dexamethasone therapy initiated just before or simultaneously with the first parenteral antibiotic dose is recommended for infants older than 6 weeks of age and children with bacterial meningitis. A beneficial effect of steroid therapy administered 12 to 24 hours or more after the first dose of parenteral antibiotics is unlikely. The consistent finding of improved overall neurologic outcome in infants and children with bacterial meningitis caused by the usual meningeal pathogens treated with dexamethasone is the basis for this recommendation, provided that the caveats discussed above are observed.
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PMID:Dexamethasone therapy in bacterial meningitis. 819 85

Detailed studies of pharmacodynamic principles relevant to the therapy of bacterial meningitis are difficult to perform in man, while the rabbit model of bacterial meningitis has proved to be extremely valuable and has led to insights that appear relevant for the treatment of humans. Most importantly in the light of the restricted penetration of antibiotics into the CSF, animal studies have shown that in meningitis there is a dose-response curve between the CSF concentrations achieved by antibiotics and their bactericidal activity. This appears to be true for all classes of antibiotics thus far examined, including the beta-lactams, which do not show such a dose-response behaviour in other infections. Only CSF concentrations that exceed the MBC of the infecting organism by at least 10-30-fold achieve consistent and rapid bactericidal activity. Such rapid bactericidal activity is a requirement for successful therapy with beta-lactams and can be impaired with certain antibiotics by the specific conditions in infected CSF (protein content; acidic pH; slow-growing bacteria). However, rapid antibiotic killing of the infecting organisms may not be without adverse effects either. Some antibiotics, particularly beta-lactams lead to the brisk liberation of bacterial cell wall components (e.g. endotoxin, in the case of Gram-negative organisms) which have an inflammatory effect on the host and can lead to a temporary deterioration of the disease. Dexamethasone, when administered with the antibiotic, can prevent some of the adverse effects of rapid bacterial lysis.
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PMID:Pharmacodynamics of antibiotics in the therapy of meningitis: infection model observations. 833 25

Accumulating evidence tends to demonstrate that inflammatory processes are responsible for neurological damage and sequelae in bacterial meningitis in children and infants. Massive liberation of bacterial cell wall components (Lipopolysaccharide, acid teichoic polymers) induce a cascade of reactions including the secretion of many cytokines (such as TNF alpha and IL-1 beta) and prostaglandins (such as PAF and PGE2) which in turn leads to the development of cerebral oedema, intracranial hypertension and cerebral blood flow reduction. Dexamethasone (DXM) is effective at the beginning of the inflammatory cascade and its utilisation in the meningitis experimental model in animals has shown significant reduction in the inflammatory response to bacterial meningitis. The first clinical studies using DXM as an adjunctive therapy to antibiotics have demonstrated its beneficial effect in terms of complications and long-term neurological sequelae in Haemophilus influenzae meningitis in children and infants. It seems that a similar effect can be obtained in meningococcal and pneumococcal meningitis. Little information is actually available concerning the use of DXM in penicillin-resistant pneumococcal meningitis. The rare reported cases of ceftriaxone failure with DXM as treatment of penicillin-resistant pneumococcal meningitis had a favorable outcome with the use of vancomycin.
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PMID:[Role of dexamethasone in the treatment of purulent meningitis in infants and in children]. 839 88

The classic triad of headache, fever and nuchal rigidity that occurs in adults with bacterial meningitis is often absent in children. Evaluation of the cerebrospinal fluid remains the gold standard for the diagnosis of bacterial meningitis. The choice of antibiotic therapy is dependent on the most likely age-specific pathogen and the drug's bactericidal activity in cerebrospinal fluid. Routine fluid restriction is no longer recommended in the initial management of critically ill patients. Dexamethasone has become an important adjunct to antimicrobial therapy for meningitis due to Haemophilus influenzae type b. Prevention, especially administration of H. influenzae type b vaccine at an early age, is probably the most effective way to reduce the significant mortality and morbidity associated with bacterial meningitis in children.
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PMID:Practical approach to bacterial meningitis in childhood. 850 45

Apoptotic neuronal death and the increase of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) were studied in a rabbit model of experimental pneumococcal meningitis after treatment with antimicrobial (ceftriaxone) and antiinflammatory agents (dexamethasone, monoclonal antibodies against the beta-subunit of beta 2-integrins [anti-CD18 mAb]). Twenty-four hours after infection, apoptotic cell death was found solely in the granular cell layer of the dentate gyrus. Neurons with DNA fragmentation were quantified with the in situ tailing (IST) reaction. Dexamethasone and anti-CD18 mAb inhibited the NSE increase in CSF significantly (p = 0.003, p = 0.011). After administration of dexamethasone the density of apoptotic neurons was significantly higher than in control animals receiving only ceftriaxone (p = 0.044). The median of the density of apoptotic neurons was lower in the dentate gyrus in animals receiving anti-CD18 mAb and ceftriaxone vs those receiving only ceftriaxone, although the difference did not reach statistic significance (p = 0.058). In conclusion, apoptotic cell death occurs in the dentate gyrus during the early phase of bacterial meningitis. The extent was influenced by antiinflammatory therapy. The systemic administration of glucocorticoids increased the quantity of apoptotic neurons in the dentate gyrus but reduced overall neuronal damage as indicated by low levels of NSE concentration in CSF.
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PMID:Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. 864 98

To investigate the role of nitric oxide (NO) in bacterial meningitis, concentrations in serum, cerebrospinal fluid (CSF), or both of the precursor (L-arginine) and degradation products of NO (nitrate, nitrite) and tumor necrosis factor (TNF)-alpha were measured in 35 patients and 30 controls. CSF nitrate levels were significantly elevated, mainly due to increased blood-brain barrier permeability, and are therefore not a good parameter for gauging endogenous NO production in the CSF compartment. CSF NO/nitrite levels were significantly elevated in patients. NO/nitrite levels decreased over time (26%/6 h; P < .001). CSF levels of NO/nitrite correlated with those of TNF-alpha (r = .55; P = .001) and glucose (r = -.43; P = .02). CSF levels of L-arginine were lower in patients than in controls (P < .001). Dexamethasone did not exert a significant effect on NO metabolism. In conclusion, enhanced NO production may contribute to anaerobic glycolysis and neurologic damage in bacterial meningitis.
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PMID:The role of nitric oxide in bacterial meningitis in children. 865 81


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