Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. Corticosteroid in tuberculous meningitis. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Randomized controlled trial of dexamethasone in tuberculous meningitis. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.
Tuberculous meningitis kills or disables more than half of those affected with the disease. Previous studies have been too small to determine whether adjunctive treatment with corticosteroids can reduce the risk of disability or death among adults with tuberculous meningitis, and the effect of coinfection with the human immunodeficiency virus (HIV) is unclear.
                We performed a randomized, double-blind, placebo-controlled trial in Vietnam in patients over 14 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adjunctive treatment with dexamethasone reduced the risk of death or severe disability after nine months of follow-up. We conducted prespecified subgroup analyses and intention-to-treat analyses.
                A total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment with dexamethasone was associated with a reduced risk of death (relative risk, 0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not associated with a significant reduction in the proportion of severely disabled patients (34 of 187 patients [18.2 percent] among survivors in the dexamethasone group vs. 22 of 159 patients [13.8 percent] in the placebo group, P=0.27) or in the proportion of patients who had either died or were severely disabled after nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13; P=0.22). The treatment effect was consistent across subgroups that were defined by disease-severity grade (stratified relative risk of death, 0.68; 95 percent confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04; P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone group than in the placebo group (26 of 274 patients vs. 45 of 271 patients, P=0.02).
                Adjunctive treatment with dexamethasone improves survival in patients over 14 years of age with tuberculous meningitis but probably does not prevent severe disability.
                Copyright 2004 Massachusetts Medical Society. In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection.
                We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization.
                A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27).
                Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499 [controlled-trials.com].).
                Copyright 2007 Massachusetts Medical Society. We assessed the benefit of prednisolone regimen in adult-patients with tuberculous meningitis by a randomised, double-blind trial. 59 patients were treated with combined antituberculous drugs and randomised to receive oral prednisolone regimen or a placebo. There were 29 and 30 patients in the treatment and placebo groups respectively. The results revealed that prednisolone was not beneficial in patients with severe brain lesions, increased intracranial pressure and cranial nerve palsies. The role of prednisolone in patients with paraparesis, visual impairment and newly developed neurological complications during treatment needs further study. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. The patients admitted to the Neurology ward of the All India Institute of Medical Sciences Hospital.
                To assess the role of dexamethasone as an adjunct to antimicrobial therapy in the treatment of tuberculous meningitis.
                A randomised controlled trial of 47 patients was conducted over a 13-month period. 41 patients completed the trial. Patients were stratified into mild, moderate and severe groups and randomly allocated to steroid and non-steroid groups. All patients received a standardized antituberculosis drug regime. The end point was 3 months, or death if earlier. The evaluation at the end point included survival, resolution of symptoms, sequelae and activities of daily living. Results were analysed using the Wilcoxon rank sum test.
                The patients in the dexamethasone group fared better. 75% of this group had mild sequelae as opposed to 62% of the control group. Amongst the survivors, those who received dexamethasone sensorium improved earlier, and there was greater improvement in mental function and daily activities. The difference, however, did not reach statistical significance.
                Dexamethasone appears useful as an adjunct in the treatment of tuberculous meningitis especially in patients who have severe disease. The results need confirmation by a larger trial. Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.
                The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.
                An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.
                Thirty-one adult CAP patients who required hospitalization were enrolled.
                Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.
                In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.
Corticosteroids should be routinely used in HIV-negative people with tuberculous meningitis to reduce death and disabling residual neurological deficit amongst survivors. However, there is not enough evidence to support or refute a similar conclusion for those who are HIV positive.