Prednisolone in the treatment of pneumococcal meningitis. Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis. Corticosteroids as an adjunct to treatment in bacterial meningitis. A controlled clinical trial. Dexamethasone in the treatment of acute bacterial meningitis: the effect of study design on the interpretation of results. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group. Dexamethasone treatment for bacterial meningitis in children and adults. Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. Beneficial effects of dexamethasone in children with pneumococcal meningitis. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group. Dexamethasone in adults with bacterial meningitis. Dexamethasone therapy for bacterial meningitis: Better never than late? Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis. Dexamethasone and bacterial meningitis in Pakistan. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Role of dexamethasone in neonatal meningitis: a randomized controlled trial. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group.
The results of a steroid on 52 Nigerians (27 males, 25 females, aged 10 to 59 years) with bacteriologically proven pneumococcal meningitis are presented. Twenty-four of the patients were treated with steroids in addition to a standard regime. The clinical features on admission in the two groups were comparable and management other than steroid administration identical. Personality change with impairment of intellect was more frequent and mortality higher in the steroid-treated group although the differences wre not statistically significant. It is concluded that steroids apparently have no beneficial effect and may worsen the prognosis in pneumococcal meningitis. We conducted a third placebo-controlled, double-blind study of dexamethasone as adjunctive therapy for bacterial meningitis. Thirty-one patients received cefuroxime sodium (300 mg/kg per day in 3 doses) and dexamethasone phosphate (0.6 mg/kg per day in 4 doses for 4 days), and 29 received cefuroxime and placebo. The groups were comparable at the beginning of therapy. Magnetic resonance imaging performed between days 2 and 5 of therapy was used to assess brain water content indirectly. There were no differences between the 2 treatment groups with respect to the T1- or T2-weighted images. Fifty-two patients (88%) had normal magnetic resonance images; 5 patients had parietal or bifrontal extra-axial fluid collections, and 2 children had areas of abnormal signal intensity in the brain on T2-weighted images. Abnormal findings on magnetic resonance imaging did not alter clinical management, and there was no correlation between the results of magnetic resonance imaging and the outcome of meningitis. The number of patients in this study was too small to determine any statistically significant differences in rates of hearing impairment; however, the cerebrospinal fluid findings and clinical outcome in dexamethasone-treated patients further support the previously reported beneficial effect of corticosteroid treatment in patients with bacterial meningitis. nan nan 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. To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults.
                Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30.
                Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion.
                Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae. Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content. Bacterial meningitis is still an important cause of death and/or persistent nervous system damage in children living in developing countries. The aim of the study was to evaluate the effectiveness of steroids in reducing mortality and neurologic sequelae in children affected by bacterial meningitis within the context of a developing country (Mozambique), where the case-fatality rate of this disease is over 30 per cent. Seventy children with bacterial meningitis were randomized to receive either conventional antibiotic therapy or antibiotic therapy plus dexamethasone. On hospital admission there were no statistically significant differences between the two groups with regard to clinical and laboratoristic features. When dexamethasone was used early mortality, within 24 h, was significantly reduced (1/34 v. 8/36, P < 0.05). Total mortality among steroid treated patients, including those who were comatose on admission, was also reduced even if the difference did not reach statistical significance. A favourable trend in terms of fewer serious neurologic abnormalities was also observed among survivors in the steroid treated patients (5/26 v. 7/24). Fever and CSF abnormalities also disappeared more rapidly in patients receiving dexamethasone (P < 0.05). This study showed that the beneficial effect of adjunctive steroid therapy in children with bacterial meningitis can be even more important in areas where the case-fatality rate of this disease is still very high. It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone.
                We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis. The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months.
                A total of 217 patients were assigned to the dexamethasone group, and 218 to the placebo group. Bacterial meningitis was confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123 patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month (relative risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with confirmed bacterial meningitis, however, there was a significant reduction in the risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98). These effects were not found in patients with probable bacterial meningitis. Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month, an observation that may be explained by cases of tuberculous meningitis in the treatment group.
                Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis; a beneficial effect appears to be confined to patients with microbiologically proven disease, including those who have received prior treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828 [controlled-trials.com] .).
                Copyright 2007 Massachusetts Medical Society. Fifty-six children older than 2 years with meningitis caused by Streptococcus pneumoniae were enrolled in a prospective, double blind, placebo-controlled trial to evaluate the efficacy of dexamethasone therapy in addition to antimicrobial therapy. Twenty-nine of 56 received dexamethasone (0.6 mg/kg/day iv, divided into 4 daily doses for 4 days) and the remaining 27 received placebo. At the beginning of therapy the clinical and laboratory characteristics of the patients in the treatment groups were comparable, except for the Glasgow coma score (P = 0.004), which was lower in the dexamethasone group. Patients were examined daily during hospitalization and 6 weeks after discharge from the hospital. Hearing was assessed 6 weeks after discharge by means of pure tone audiometry. Two patients in the dexamethasone group and one patient in the placebo group died. There were no differences between the two groups with regard to the duration of fever, the incidence of secondary fever and electrolyte imbalance, seizure activities occurring during hospitalization and rash. Although the differences were statistically insignificant, moderate or severe unilateral or bilateral sensorineural hearing loss at 6 weeks and the overall neurologic sequelae, including hearing loss, at 1 year were higher in the placebo group, at 23% vs. 7.4% (P = 0.11) and 26.9% vs. 7.4% (P = 0.062), respectively. At 3 months after discharge, because of the improvement in hearing loss in one dexamethasone-treated patient the incidence of hearing impairment was significantly less than that in the placebo group, at 3.7% vs. 23%, respectively (P = 0.044). No improvement in hearing loss was observed after 3 months.(ABSTRACT TRUNCATED AT 250 WORDS) We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness. To assess the value of adjunctive intravenous dexamethasone (DXM) and oral glycerol (GLY) for the treatment of bacteriologically proved bacterial meningitis, 122 infants and children with bacterial meningitis were randomly assigned to receive DXM intravenously (n = 32), GLY orally (n = 30), DXM plus GLY (n = 34) or neither (n = 26) of these drugs. All patients were treated with the same antimicrobial agent, ceftriaxone. The patients were followed neurologically for as long as 6 months. A thorough hearing evaluation was performed routinely 2 months or more after discharge from hospital. Overall 4 (7%) of the GLY-treated patients, compared with 11 (19%) of those not given GLY, developed audiologic or neurologic sequelae (P = 0.052), the relative risk of sequelae being 2.94 (95% confidence interval, 0.99 to 8.72). The patients who had received GLY showed less severe or profound bilateral hearing impairment than those not given GLY (0 vs. 7%, P = 0.049), and none of them had other neurologic abnormalities 3 or 6 months after discharge, compared with 5 (9%) of those not treated with GLY (P = 0.024). The DXM recipients showed only a tendency to less severe hearing impairment than those not given DXM. In conclusion oral GLY prevented neurologic sequelae in infants and children with bacterial meningitis more effectively than intravenous DXM. Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
                We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.
                A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.
                Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.
                Copyright 2002 Massachusetts Medical Society A multicentre randomized controlled trial was conducted in children with bacterial meningitis using dexamethasone or placebo for four days within 24 h of starting antibiotics. Primary outcomes were hearing loss and neurological abnormalities at 12 months after meningitis. The dexamethasone (n=50) and placebo (n=51) groups were similar in age, severity of illness and etiological agent. Hearing loss occurred in 10% and 11% of the dexamethasone and placebo groups and neurological deficits occurred in 20% and 18% of patients, respectively. Duodenal perforation occurred in one dexamethasone-treated child. In conclusion, there was no significant benefit in those receiving dexamethasone. The lack of benefit may have been due to the delay in administration of dexamethasone (median delay of 11 h after antibiotics). Therefore, if dexamethasone is used for meningitis it should be given immediately with the antibiotic. To investigate the efficacy of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with acute bacterial meningitis (ABM).
                Prospective double blind, placebo controlled randomized study.
                Pediatric services of a tertiary care teaching and referral hospital.
                Children 2 months to 12 years with a diagnosis of acute bacterial meningitis admitted between June 2002 to September 2003.
                Subjects were assigned randomly to receive dexamethasone, glycerol, dexamethasone+glycerol or placebo. Neurological and hearing impairment was assessed at discharge and after 1 month.
                58 children (48 boys, 10 girls), mean age 50.2 +/- 41.0 months, were studied. Twelve patients received dexamethasone, 13 glycerol, 20 dexamethasone + glycerol and 13 placebo. Bacterial etiology was ascertained in 24 patients: Streptococcus pneumoniae-10, H influenzae b-7, Staph. aureus-5 and others-2. Three (5.2%) children died during hospital stay and 55 survived. Seven (12%) patients had neurological sequelae (3 in glycerol, 3 in dexamethasone+glycerol, 1 in placebo group, P = 0.29), and 10 patients (17%) had hearing sequelae (2 in glycerol, 3 in dexamethasone, 2 dexamethasone + glycerol and 3 in placebo group, P = 0.68).
                No significant difference was seen in neurological or hearing outcome with use of either glycerol or dexamethasone in children with acute bacterial meningitis. 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. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease.
                We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days.
                The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5).
                The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis. Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually.
                We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models.
                H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014).
                Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings. To evaluate the role of dexamethasone therapy in neonatal meningitis in a randomized placebo controlled trial.
                The participants were eighty neonates with meningitis randomized to receive dexamethasone or saline placebo. Dexamethasone was started prior to the first dose of antibiotics in the dose of 0.15 mg/kg intravenous 6 hourly for 2 d. Primary outcome measure was mortality. Secondary outcome measures included progression of systemic inflammatory response syndrome (SIRS) up to 48 h, differences in cerebrospinal fluid (CSF) cytokines between baseline levels and 24 h after enrolment and brain stem auditory evoked response (BAER) after 4 to 6 wk of discharge.
                Baseline variables were comparable in both the groups. Mortality was significantly decreased in dexamethasone group (p = 0.005) and the absolute risk difference was 27.5 % (95 % CI 9.5-45.8 %). There was a significant reduction in cells per mm(3) (62.5 vs. 100) and proteins (162 vs. 217.5 mg/dl) after 24 h of treatment in the dexamethasone group. IL-1β was significantly reduced after 24 h in dexamethasone group (290 vs 665 pg/ml). TNF- α was significantly lower (157.5 vs 427.5 pg/ml) and sugar significantly higher (50 vs 38 mg/dl) in the dexamethasone group after 24 h. Significant difference was noted between dexamethasone and saline groups in the progression of SIRS.
                Dexamethasone significantly reduced fatality, progression of SIRS and CSF inflammatory indices. Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion. We aimed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country.
                In a double-blind, placebo controlled trial, we included 598 children with pyogenic meningitis who had been admitted to the children's wards of the Queen Elizabeth Central Hospital, Blantyre, Malawi. We did physical, neurological, developmental, and hearing assessments at 1 and 6 months after discharge. The primary outcome was overall death. Secondary outcomes included sequelae, in-hospital deaths, and death after discharge. Analysis was done by intention to treat.
                Of the 598 included children, 307 (51%) were assigned to dexamethasone and 295 (49%) to placebo. 338 (40%) of 598 patients had Streptococcus pneumoniae, 170 (28%) Haemophilus influenzae type b, 66 (11%) Neisseria meningitidis, and 29 (5%) Salmonella spp. 78 (13%) patients had no growth on culture. The number of overall deaths was the same in the two treatment groups (relative risk 1.00 [95% CI 0.8-1.25], p=0.93). At final outcome, sequelae were identified in 84 (28%) of children on steroids and in 81 (28%) on placebo (relative risk 0.99 [95% CI 0.78-1.27], p=0.97). The number of children dying in hospital did not differ between groups.
                Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries. 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.
Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.