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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 this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.
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PMID:Dexamethasone and bacterial meningitis in Pakistan. 901 99

Dexamethasone appears to show some adverse side-effects as adjunctive anti-inflammatory agent in bacterial meningitis. For this reason, we tested the anti-inflammatory and neuroprotective effect of pentoxifylline administered 15 min before starting antibiotic treatment with ceftriaxone (n = 10) versus antibiotic therapy alone (n = 9) in the rabbit model of pneumococcal meningitis. Pentoxifylline lowered the medians of leucocyte density, tumour necrosis factor-alpha (TNF-alpha) and lactate in the cerebrospinal fluid (CSF), but only leucocyte migration into the subarachnoid space was significantly inhibited 8 h after initiation of therapy (P = 0.01). CSF protein, brain water content, and the entry of ceftriaxone into CSF were not influenced by pentoxifylline. The density of neuronal apoptoses in the dentate gyrus was slightly lower in animals receiving pentoxifylline than in those treated with ceftriaxone only. The median concentration of neuron-specific enolase in CSF was lower in the pentoxifylline-treated group, but the difference was not significant. In conclusion, pentoxifylline showed some anti-inflammatory activity in pneumococcal meningitis, but the substance failed significantly to reduce neuronal damage.
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PMID:Limited efficacy of pentoxifylline as anti-inflammatory agent in experimental pneumococcal meningitis. 906 17

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. Animal and clinical trials have demonstrated that adjunctive corticosteroid therapy reduces the production of cytokines in the CSF. This results in decreased severity of the inflammatory process and fewer neurologic sequelae. However, routine use of steroids adjunctive treatment of bacterial meningitis remains controversial. Data support the use of adjunctive corticosteroid therapy in children with S. pneumoniae and H. influenzae type b meningitis. There is not sufficient evidence supporting the use of adjunctive corticosteroid therapy in patients with meningitis caused by N. meningitidis, which is the main cause of purulent meningitis in Poland. Also, the routine use of the dexamethasone in children and adult meningitis in Poland cannot presently be recommended. When using dexamethasone timing and dosage seems to be crucial. Administration before or with antibiotics is optimal for attenuating the subarachnoid space inflammatory response. The host's inflammatory response can be accompanied by the neuroendocrine response which is complex and its mediators are not well understood. Data indicate that the large component of the neuroendocrine response (e.g. inadequate secretion of ADH and large adrenocortical stress response) adversely affects the outcome from bacterial meningitis. So, the modulating effect of dexamethasone on both inflammatory and neuroendocrine response may be beneficial in bacterial meningitis and can probably be, achieved with sufficiently high dose of dexamethasone w has not yet been specified. Based on present pathophysiological and pharmacokinetic data, and to achieve maximum benefits and minimum complications, dexamethasone therapy started 10 min before the first dose of antibiotic and given every 12 h for only 2 days in a dose 0.8 mg/kg/day is suggested. Future studies of the pathogenesis and pathophysiology of bacterial meningitis may lead to the development of other adjunctive treatment strategies, improving the outcome of this serious disease.
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PMID:[Supportive (antiinflammatory) treatment of bacterial meningoencephalitis with dexamethasone]. 937 71

Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Streptococcus [corrected] pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin. Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs. placebo: 33. 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P=.0003). These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection.
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PMID:Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac. 984 52

This study characterised the levels of serum immunoglobulin G (IgG), cerebrospinal fluid IgG (CSF IgG) and IgG index as an aid to the diagnosis and prognosis of acute bacterial meningitis (ABM). A total of 28 patients with proven ABM at admission (age range: one month to 10 years; 17 males, 11 females) (group A) and 17 age- and sex-matched control children (group B) were studied. Levels were also compared between patients with neurological morbidity (n = 4; group C) and without neurological morbidity (n = 24; group D) who were subsets of group A. In addition, patients were divided randomly into two groups based on the treatment received (i.e. ceftriaxone together with dexamethasone [n = 11; group A1] and ceftriaxone only [n = 9; group A2] to assess the effect of dexamethasone. The results (mean +/- SEM) demonstrated intrathecal synthesis of IgG in ABM (group A vs group B: CSF IgG (mg/L): 92.64 +/- 23.54 vs 2.12 +/- 1.08, P < 0.002; IgG index: 0.959 +/- 0.481 vs 0.029 +/- 0.006, P < 0.001) which showed good diagnostic significance. In the patients with permanent neurological morbidity (group C) vs healthy survivors (group D), the CSF IgG and IgG index showed good prognostic significance (group C vs group D: CSF IgG (mg/L): 10.75 +/- 9.75 vs 106.24 +/- 29.37, P < 0.01; IgG index: 0.046 +/- 0.039 vs 1.132 +/- 0.568, P < 0.05). Dexamethasone lowered CSF-IgG and IgG-index levels, but the effect was not statistically significant (group A1 vs group A2: P > 0.1).
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PMID:Levels of serum immunoglobulin G, CSF IgG and IgG index in acute bacterial meningitis. 1043 40

This study was conducted on 77 Libyan infants and children aged month to 10 years with acute bacterial meningitis. Upon admission, the patients were divided randomly in two groups. Group I (38 patients) received ceftriaxone plus dexamethasone i.v. Group II (39 patients) received ceftriaxone alone. Both groups were compared for mean changes in CSF sugar, CSF protein and CSF polymorph count at 4th day of treatment. There was a significant difference between the two groups in CSF sugar and protein changes (P < 0.05) but not in CSF polymorph (P > 0.05). Both groups showed prompt clinical response and similar occurrence of acute complications, fatality rate and permanent neurological sequelae. However, group I manifested shorter duration of fever (P < 0.05). Dexamethasone improved the inflammatory reaction in acute bacterial meningitis and shortened the duration of fever but it did not have any significant effect on the fatality and the occurrence of neurological sequelae of this disease.
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PMID:Dexamethasone as an adjunctive treatment of bacterial meningitis. 1077 81

Permanent neurologic disabilities are seen in up to a quarter of survivors of bacterial meningitis despite major improvements in therapy. Experimental studies have demonstrated that most of the pathology in meningitis is mediated by inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which are produced by host cells in response to bacterial invasion of the meninges. Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients when Haemophilus influenzae type b (Hib) was the causative agent of meningitis. Following routine use of Hib vaccine, meningitis caused by this agent has virtually disappeared in the USA. Hence, findings from these trials may no longer be applicable in countries with high rates of immunization against Hib. Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused by S. pneumoniae or N. meningitidis. Global emergence of penicillin and cephalosporin resistant S. pneumoniae has raised new concerns about the use of dexamethasone in pneumococcal meningitis. Since dexamethasone significantly decreases the penetration and concentration of vancomycin and ceftriaxone in the CSF and delays CSF sterilization, adjunctive dexamethasone therapy may increase the risk of treatment failure in meningitis caused by antibiotic resistant pneumococci. An antibiotic combination should be used in the treatment of meningitis caused by antibiotic resistant pneumococci, particularly if dexamethasone is also being administered concurrently.
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PMID:Dexamethasone in bacterial meningitis: to use or not to use? 1083 26

Initial empiric therapy for community-acquired bacterial meningitis should be based on the possibility that penicillin-resistant pneumococci may be the etiologic organisms and, hence, should include a combination of third-generation cephalosporin (cefotaxime or ceftriaxone) and vancomycin. Ampicillin should be included if the patient has predisposing factors that are associated with a risk for infection with Listeria monocytogenes. Bacterial isolates from the cerebrospinal fluid should be tested for antimicrobial susceptibility. Understanding the significance of inflammatory cytokines in the pathophysiology of bacterial meningitis leads to an understanding of the need to prevent their formation. Dexa- methasone inhibits synthesis of the inflammatory cytokines, interleukin-1 and tumor necrosis factor. Results of clinical trials and meta-analysis suggest that dexamethasone therapy improves the outcome for patients with bacterial meningitis. Dexamethasone should be administered before or with the first dose of antibiotics. The development of therapeutic modalities to downregulate host inflammatory responses, such as those of monoclonal antibodies to cytokines, is of utmost importance.
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PMID:Bacterial Meningitis. 1109 4

Nitric oxide is very likely to play a role in physiopathological mechanisms of bacterial meningitis. As shown by in vitro studies, nitric oxide is toxic to endothelial cells, as well as to neurones, and thus may be responsible for neurological sequelae in bacterial meningitis. Increased level of nitric oxide can also inhibit mitochondrial respiration, enhancing anaerobic glycolysis. Twenty-seven children with documented bacterial meningitis, 73 with viral (mumps and enteroviral) meningitis, and 51 controls were studied. All children with bacterial meningitis were given cefotaxime (200 mg/kg per day). Glucose and protein concentrations and cerebrospinal fluid cell counts were determined routinely, as well as nitrite and nitrate levels. The levels of nitrite and nitrate in cerebrospinal fluid on admission were higher in patients with bacterial meningitis than in controls or in children with viral meningitis. In 10 patients, dexamethasone therapy (0.4 mg/kg every 12 h for 2 days) was started about 10 min before the first antibiotic dose. A significantly lower nitrite concentration was observed after 24-48 h of treatment compared with non-steroid-treated patients. Significant positive correlations between the nitrite and granulocyte counts and the protein concentration in cerebrospinal fluid were found in all patients with meningitis. Increased nitric oxide production in cerebrospinal fluid during the acute phase of bacterial meningitis may result from the inflammatory process and tissue injury. Dexamethasone administered before the first parenteral antibiotic dose seems to reduce nitric oxide production in the cerebrospinal fluid during bacterial meningitis.
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PMID:Nitric oxide production during bacterial and viral meningitis in children. 1119 70

During the past decade antibiotic resistance among Streptococcus pneumoniae isolates has complicated the empiric approach to and treatment of pneumococcal meningitis. Standard empiric therapy for suspected bacterial meningitis for infants and children older than 1 month of age is the combination of cefotaxime or ceftriaxone and vancomycin. Treatment is modified after antimicrobial susceptibilities are available. The optimal treatment of pneumococcal meningitis caused by strains with a cefotaxime/ceftriaxone MIC >2 microg/ml is unknown, although the addition of rifampin to the initial combination is generally recommended. The role of newer agents including quinolones is under investigation. Dexamethasone remains the only adjunctive antiinflammatory therapy to consider. The empiric approach to the child with suspected bacterial meningitis who has received the pneumococcal conjugate vaccine currently remains unchanged.
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PMID:Management of pneumococcal meningitis. 1218 95


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