Dexamethasone and bacterial meningitis in Pakistan. Beneficial effects of dexamethasone in children with pneumococcal meningitis. Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis. Antiviral treatment of idiopathic sudden sensorineural hearing loss: a prospective, randomized, double-blind clinical trial. Treatment of idiopathic sudden sensorineural hearing loss with antiviral therapy: a prospective, randomized, double-blind clinical trial. Dexamethasone treatment for bacterial meningitis in children and adults. Corticosteroid treatment of idiopathic sudden sensorineural hearing loss: randomized triple-blind placebo-controlled trial. Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.
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. 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) 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. A subclinical viral labyrinthitis has been postulated in the literature to elicit Idiopathic Sudden Sensorineural Hearing Loss. An etiological role for the herpes virus family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, the therapeutic value of the antiherpetic drug aciclovir (Zovirax) on hearing recovery in 44 ISSHL patients receiving prednisolone is evaluated in a multicentre clinical trial. The study is designed prospectively, randomized, double-blind and placebo-controlled. Subjective parameters include hearing recovery, a pressure sensation on the affected ear, disequilibrium or vertigo and tinnitus. Audiometric parameters include pure tone and speech audiometry. A one-year follow up is obtained. Both the pressure sensation and disequilibrium or vertigo have a good prognosis, but tinnitus, occurring in most patients, has a poor prognosis. Hearing recovery prognosis depends on the severity of initial hearing loss, and not on vestibular involvement. No beneficial effect from combining aciclovir with prednisolone can be established in ISSHL. A subclinical viral labyrinthitis has been postulated in the literature to elicit idiopathic sudden sensorineural hearing loss (ISSHL). An etiologic role for the herpes family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, we evaluated the therapeutic value of the antiherpetic drug acyclovir (Zovirax) on hearing recovery in 91 patients with ISSHL who received prednisolone in a prospective, randomized, double-blind, placebo-controlled, multicenter trial. The audiometric parameters included pure tone and speech audiometry. Subjective parameters studied included hearing recovery, a pressure sensation in the affected ear, vertigo, and tinnitus. A 1-year follow-up was obtained. Hearing recovery for the whole group averaged about 35 dB and was independent of the severity of the initial hearing loss or vestibular involvement. Speech audiometry improved from 49% to 75%. After 12 months, pressure sensation and vertigo decreased to 15.6% (acyclovir) and 10.3% (placebo) and 12.5% (acyclovir) and 10.7% (placebo), respectively. Tinnitus decreased slightly, to 46.9% (acyclovir) and 55.2% (placebo), in the same period (p > .05 for all parameters). We conclude that no beneficial effect from combining acyclovir with prednisolone can be established in patients with ISSHL. 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. To compare the effect of Prednisolone and placebo on the recovery of unilateral idiopathic sudden sensorineural hearing loss.
                Prospective, randomized, triple-blind, placebo-controlled multicenter trial.
                Four tertiary and 10 secondary referral centers.
                Of 103 patients randomly assigned, 93 were included in the modified intention-to-treat analysis. The patients, aged 18 to 80 years, were seeking care within 1 week after onset of acute unilateral sensorineural hearing loss with a mean decrease of 30 dB or greater in the 3 most affected contiguous frequencies.
                Patients were randomly assigned in permuted blocks of 10 to receive Prednisolone or placebo in tapering doses from 60 mg for 3 days and, thereafter, 10 mg less each day until Day 8. If complete recovery, no more medication given, otherwise medication continued at 10 mg per day until Day 30. Final follow-up was after 3 months with audiogram; 47 patients received Prednisolone and 46 placebo.
                The primary endpoint was efficacy of treatment on recovery at Day 90. Secondary endpoints were prognostic factors for hearing recovery. Analyses were by modified intention-to-treat and per protocol.
                Hearing improvement for 47 Prednisolone-treated patients was 25.5 ± 27.1 dB compared to 26.4 ± 26.2 dB for 46 placebo-treated patients at Day 8 and 39 ± 20.1 dB versus 35.1 ± 38.3 dB after 3 months. Vertigo had significant negative effect on hearing improvement and inflammatory signs in the laboratory workup-a positive prognostic effect, irrespective of treatment.
                Prednisolone in customary dosage does not seem to influence recovery of idiopathic sudden sensorineural hearing loss. 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. 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.
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.