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Steroid and meningitis

Studies have also found that meningitis treatment with steroids significantly reduce the risk of death in adults. To be helpful, a steroid must be given right away. This will help prevent swelling and pressure in the brain and subsequent neurological complications. Most children and adults of all ages can take steroids — the only exception is very young babies.

A number of studies have shown that meningitis treatment with steroids clearly reduces the chance of deafness, and may lessen mortality as well. In one review of 18 of those studies involving 2, patients, steroids appeared to reduce the risk of severe hearing loss in children.

Additionally, an earlier study published in the British Medical Journal found that death among adult meningitis patients taking steroids was less than half that of patients not receiving steroids. Study results have been mixed regarding fatality reductions in children, however. When test results rule out bacterial meningitis, steroids are typically stopped. Some doctors are also concerned that steroids could decrease the penetration of antibiotics into the fluid around the brain and spinal cord where bacteria reside, but not all experts agree about this.

Research on the use steroids to treat meningitis is continuing at a number of medical centers around the country. By subscribing you agree to the Terms of Use and Privacy Policy. Health Topics. We identified 25 trials, including participants with acute bacterial meningitis of which seven were performed in adults over 16 years old , two included both children and adults and the other were performed in children. In 22 studies the corticosteroid used was dexamethasone, in three others hydrocortisone or prednisone were used.

This review found that the corticosteroid dexamethasone did not significantly reduce the death rate Patients treated with corticosteroids had significantly lower rates of severe hearing loss 6. An analysis for different bacteria causing meningitis showed that patients with meningitis due to Streptococcus pneumoniae S pneumoniae treated with corticosteroids had a lower death rate Out of 25 studies, four were of high quality, 14 of medium quality and seven of low quality, leading to a moderate overall quality of evidence.

Bacterial meningitis is a severe infection of the meninges the membrane lining of the brain and spinal cord that is associated with high mortality and morbidity rates despite optimal antibiotic therapy and advances in critical care Baraff ; Bohr ; Brouwer c ; van de Beek ; van de Beek b ; van de Beek b. Intravenously or orally administered corticosteroids, such as prednisolone, hydrocortisone and dexamethasone, are given before, with or after antibiotic treatment for suspected or proven bacterial meningitis.

In experimental animal studies, the outcome of meningitis worsens with increasing severity of the inflammatory process in the subarachnoidal space Scheld ; Tauber Treatment with corticosteroids was shown to result in a reduction of the inflammatory response in the cerebrospinal fluid CSF , reversal of brain oedema and improved outcome Scheld ; Tauber These pathophysiological insights prompted investigators to evaluate corticosteroids as an adjuvant therapy in acute bacterial meningitis.

In the s two randomised controlled trials RCTs evaluated the effect of corticosteroids in patients with bacterial meningitis Bennett ; DeLemos New randomised clinical trials were performed in the late s and s Lebel a ; Lebel b ; Lebel ; Odio , with conflicting results. New trials were performed in children with bacterial meningitis, most commonly caused by Streptococcus pneumoniae S pneumoniae.

In the s, five large randomised clinical trials have been performed. Two trials in children were performed in Malawi and South America and three trials in adults were performed in Europe, Vietnam and Malawi de Gans ; Molyneux ; Nguyen ; Peltola ; Scarborough The European trial showed a beneficial effect in all patients, with the most apparent effect on mortality and unfavourable outcomes in pneumococcal meningitis de Gans The Vietnamese trial showed a beneficial effect only in patients with proven bacterial meningitis Nguyen The other trials did not show a beneficial effect.

However, a post hoc analysis did show a reduction in any hearing loss in surviving patients treated with dexamethasone. The results of many trials have been inconclusive and most studies have been relatively small. Trials have varied greatly in study population, study design, timing and dosage of corticosteroids. See Appendix 1 for a glossary of terms. Hearing loss was defined as severe when there was bilateral hearing loss greater than 60 dB or requiring bilateral hearing aids. We analysed any hearing loss and severe hearing loss separately.

Neurological sequelae were defined as focal neurological deficits other than hearing loss, epilepsy not present before meningitis onset , severe ataxia and severe memory or concentration disturbance. Whenever possible, we extracted data for both these outcomes.

Details of earlier searches are in Appendix 2. We did not apply any language or publication restrictions. Besides the electronic search we identified relevant trials by searching references listed in published studies, handsearching congress abstracts, personal communication with researchers and experts in the field and from literature lists of pharmaceutical companies.

Two review authors MD, DvdB independently screened the search results and retrieved the full articles of all potentially relevant trials. We scrutinised each trial report to ensure that multiple publications from the same trial were included only once. We resolved disagreements through discussion and listed the excluded studies and the reasons for their exclusion.

Data extracted included study design, inclusion criteria, patients' characteristics, country in which the study was performed, intervention characteristics and outcome measures. We resolved disagreements through discussion and contacted the corresponding publication author in the case of unclear or missing data.

For dichotomous outcomes, we recorded the number of participants experiencing the event and the number randomised in each treatment group. For each study we completed a 'Risk of bias' table, scoring for adequacy of sequence generation, allocation concealment, blinding, if incomplete data were addressed, selective reporting and other sources of bias Higgins All outcome measures were dichotomous. We contacted the corresponding publication author in the case of unclear or missing data.

If details were not provided, results used in the analysis were as provided in the publication. We scored missing data in the outcome measures severe hearing loss and neurological sequelae for each study if reported. We assessed whether missing data were equally distributed between treatment and control groups using the Chi 2 test. We conducted visual inspection of the funnel plot of the studies for any obvious asymmetry that could indicate publication bias.

We analysed the data using Review Manager 5. Two age groups were defined: patients younger than 16 years and those aged 16 years and older. Three categories of causative organisms were defined: H influenzae , Neisseria meningitidis N meningitidis and S pneumoniae.

Studies were divided into three categories of methodological quality: high, medium and low according to the score in the 'Risk of bias' table. If all questions in the 'Risk of bias' table were answered positively we categorised the study as high quality, three through five as medium quality and less than three questions answered positively as low quality. We considered all participants who had dropped out of the corticosteroid group to have an unfavourable outcome whereas we considered those who had dropped out of the control group to have a favourable outcome.

We conducted a sensitivity analysis by imputing the missing data in this way to determine whether the overall results were sensitive to this assumption. Finally, we performed the analyses for the primary outcome measures without studies with unclear or unknown sequence generation. Since the first publication of this review we have retrieved a total of records. After removing duplicates we identified records in the electronic databases.

In the previous publications of this review, Brouwer , we identified 40 potentially eligible trials, of which two were described in one paper Lebel a ; Lebel b. Two papers presented data from one study Sankar ; Singhi In this search we did not identify any new trials for inclusion. These studies included patients dexamethasone, placebo.

Participants over 16 years were included in seven studies patients: dexamethasone, placebo Bhaumik ; de Gans ; Girgis ; Nguyen ; Scarborough ; Thomas In two studies, participants older than 12 years were considered adults Bhaumik ; Girgis The study intervention consisted of dexamethasone in 22 out of 25 studies; dosages ranged from 0. In the other studies hydrocortisone, prednisolone or a combination of both were given and duration ranged from three to 14 days Bademosi ; Bennett ; DeLemos Study medication was administered before or with the first dose of antibiotics in 13 studies, and after the first dose in eight studies.

In four studies the time of administration was not stated. A sample size calculation was given in eight studies de Gans ; Mathur ; Molyneux ; Nguyen ; Peltola ; Qazi ; Scarborough ; Thomas Definitions of adverse events were heterogeneous and we recalculated the number of events for each study. There were no disagreements on inclusion or exclusion of studies between the review authors extracting study data. No study authors needed to be contacted to provide additional information for this updated version of the review.

Ten studies were funded in part by pharmaceutical companies, which were often only providing study medication. Five studies were funded by charities, four by government funding organisations, and funding was not reported for nine studies. We excluded 16 trials Characteristics of excluded studies. Three studies did not randomise between treatment and control groups Marguet ; Ozen ; Tolaj Nine trials did not adequately generate a randomisation sequence and in most of these alternate allocation schemes were used Ayaz ; Baldy ; Daoud ; Gijwani ; Gupta ; Jensen ; Lepper ; Passos ; Shembesh One study compared two dexamethasone regimens Syrogiannopoulos , one was a duplicate study Singhi , and one study provided insufficient data communications during scientific meetings only Farina Four of 25 studies were free of bias, whereas the other 21 had one or more biases.

Attrition, reporting and potential selection bias were most common, occurring in eight, 18 and 12 studies Figure 1. The sequence generation for participant allocation was adequate in 20 studies. In five studies the method of sequence generation was unclear or not specified Bademosi ; Belsey ; Bennett ; Ciana ; King Figure 2 ; Figure 1. In five studies the treatment allocation was not concealed Bademosi ; Bhaumik ; Ciana ; Girgis ; Kilpi , and in one study treatment allocation concealment was unclear as participants were paired for placebo or dexamethasone Belsey However, some centres did not include participants in the double placebo group, thereby disturbing the allocation concealment Peltola ; van de Beek Missing data were addressed in 16 studies and were not addressed in eight Bademosi ; Belsey ; Bennett ; Bhaumik ; Girgis ; Kanra ; Schaad ; Thomas One study reported having complete data for all included participants Mathur Out of survivors who were included in studies that analysed severe hearing loss, 8.

Data on any hearing loss were missing in of 7. None of the trials registered a study protocol in a trial registry. In 12 studies differences in baseline and clinical characteristics between treatment and control groups influenced comparability of groups Bademosi ; Belsey ; Bhaumik ; DeLemos ; Kanra ; Kilpi ; Lebel ; Mathur ; Peltola ; Sankar ; Thomas , indicating either insufficient sample size to equal out the random differences between randomisation arms or a selection bias.

Nine studies did not present sufficient participant characteristics to determine whether the participants in each randomisation arm were comparable. See: Table 1. Adverse events were recorded in 20 studies: 16 evaluated gastrointestinal haemorrhage, 12 recurrent fever, six reactive arthritis, five herpes zoster, three persistent fever and one fungal infections Belsey ; Bennett ; Bhaumik ; de Gans ; Kanra ; Kilpi ; King ; Lebel a ; Lebel b ; Lebel ; Mathur ; Nguyen ; Odio ; Peltola ; Qazi ; Sankar ; Scarborough ; Schaad ; Thomas ; Wald Analysis 1.

Participants treated with corticosteroids had an increase in recurrent fever RR 1. Other complications occurred in similar proportions of the treatment and control groups. Corticosteroids prevented hearing loss in children: any hearing loss was found in of Out of participants with H influenzae meningitis, 87 died Corticosteroids protected against death in pneumococcal meningitis RR 0.

For children with meningitis caused by H influenzae , hearing loss was significantly reduced by corticosteroids RR 0. For children with meningitis caused by bacteria other than H influenzae , no significant beneficial effect was seen RR 0. Subgroup analysis on timing of corticosteroids before or with the first dose of antibiotics versus after the first dose of antibiotics showed similar results for mortality RR 0.

We analysed studies in three categories of study quality according to the studies' 'Risk of bias' score Figure 1. Four studies including participants were categorised as high quality de Gans ; Molyneux ; Nguyen ; Scarborough , 14 studies with participants as medium quality DeLemos ; Kanra ; King ; Lebel a ; Lebel b ; Lebel ; Mathur ; Odio ; Peltola ; Qazi ; Sankar ; Sankar ; Schaad ; Thomas ; Wald , and seven studies including participants as low quality Bademosi ; Belsey ; Bennett ; Bhaumik ; Ciana ; Girgis ; Kilpi Severe hearing loss was reduced in studies of medium quality RR 0.

Results for other primary outcome measures did not differ from the initial analyses. Overall, corticosteroids significantly reduced the rate of hearing loss risk ratio RR 0. Subgroup analyses for age showed that in children with bacterial meningitis, corticosteroids prevented severe hearing loss RR 0. Subgroup analysis for causative organism showed that corticosteroids reduce severe hearing loss in children with meningitis due to H influenzae RR 0.

Subgroup analysis on S pneumoniae showed a favourable effect of corticosteroids on mortality RR 0. No effect on mortality was shown in H influenzae meningitis. Corticosteroids were protective against severe hearing loss RR 0. In this study physicians were not blinded to the treatment groups.

Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics; of glucocorticoids, dexamethasone has superior penetration in the cerebrospinal fluid CSF and a longer half life Balis Therefore, dexamethasone is considered to be the corticosteroid of choice in bacterial meningitis. Subgroup analyses for timing of corticosteroids before or with the first dose of antibiotics versus after the first dose of antibiotic showed no differences in efficacy of corticosteroids.

In previous reports, administration of corticosteroids before or with the first dose of parenteral antibiotics seemed to be more effective than administration after the first dose of antibiotics King ; McIntyre A RCT involving adults with bacterial meningitis in European countries showed a beneficial effect of the corticosteroid dexamethasone on unfavourable outcome and mortality de Gans In this European study, dexamethasone or placebo was administered before or with the first dose of antibiotic de Gans The beneficial effect of dexamethasone on mortality was most apparent in patients with pneumococcal meningitis.

In a post hoc analysis of this study, the beneficial effect of dexamethasone on mortality in patients with pneumococcal meningitis was attributable to a reduction in systemic complications van de Beek a. Although speculative and not supported by clinical data, one implication of this finding might be that the effect of dexamethasone is not restricted to the first hours after administration van de Beek b.

Data from patients from five trials were included and the aim of this analysis was to establish whether any subgroups of patients with acute bacterial meningitis might benefit from adjunctive dexamethasone. There were no differences in efficacy of adjunctive dexamethasone with regard to the timing of corticosteroids. Hence, there is a time period beyond which corticosteroid loses its effectiveness after the first parenteral administration of an antibiotic agent but this time interval has not been clearly defined.

On the basis of the available evidence, dexamethasone should be preferably started before or with the first dose of antibiotic therapy. The study included of evaluable participants surviving the initial trial period. The authors conclude that the beneficial effect of dexamethasone that is obtained in the acute phase of the disease remains for years.

In children with acute bacterial meningitis, corticosteroids reduced hearing loss from However, as conclusive evidence is lacking for this subgroup, administration of corticosteroids to children with meningitis due to bacteria other than H influenzae remains controversial. Only one study in this analysis involved children with neonatal meningitis and showed a beneficial effect of corticosteroids on outcomes Mathur Additional RCTs evaluating corticosteroids in neonatal meningitis need to be performed before definitive conclusions can be drawn on the role of dexamethasone treatment in neonatal meningitis.

The use of steroids was associated with fewer cases of persistent fever and more cases of recurrent fever, but not with serious adverse events. Therapeutic failures have been described in adults treated with standard doses of vancomycin and adjunctive dexamethasone Viladrich However, two studies showed with repeated lumbar punctures that, in both adults and children, treatment with dexamethasone did not reduce vancomycin levels in the CSF Klugman ; Ricard Although these results are reassuring, patients with pneumococcal meningitis who are treated with vancomycin and dexamethasone should still be carefully observed throughout therapy van de Beek a.

In adults who survive acute bacterial meningitis, cognitive impairment occurs frequently van de Beek ; van de Beek a. As corticosteroids may potentiate ischaemic injury to neurons Sapolsky , it is important to know whether corticosteroids have beneficial effects on hearing loss and mortality but worsen cerebral cortical functioning van de Beek b.

Neuropsychological outcome was evaluated in patients included in the European Dexamethasone Study who survived pneumococcal or meningococcal meningitis Weisfelt For the analysis on severe hearing loss, significant heterogeneity between trials of high, medium and low quality was found.

When this study was left out a trend towards benefit of dexamethasone on any hearing loss was found Molyneux Several biases may have diminished the reliability of our results. The first confounding factor is selection bias. For patients admitted in a late state of disease, adjuvant corticosteroids are less protective and might even be harmful Prasad Inclusion of such patients might again lead to an underestimation of the treatment effect. A second bias is introduced when participants are withdrawn Prasad ; Qazi A total of participants were withdrawn after the randomisation process, often for unknown reasons.

Reasons for withdrawal include ineligibility according to the trial criteria or inability to complete the treatment protocol Prasad Withdrawals on the grounds on ineligibility may have been influenced by knowledge of outcome; if so, this would advantage the corticosteroid regimen. A third bias is introduced by competing risks. The comparisons of hearing loss and neurologic sequelae other than hearing loss were made excluding all participants who died. Competing risks in this analysis will lead to an underestimation of the treatment effect of corticosteroids.

Finally, the included studies were heterogeneous with respect to the study protocols. The first study was published in Bennett , the last in Mathur Several different study interventions were used. Therefore, study population effect sizes were calculated as risk ratios.

However, other countries that were included had only slightly higher HDIs at the time of inclusion Girgis , Egypt 0. According to the classification of study quality used, most of these studies were of similar quality to those that were included. There may be several reasons for the difference in efficacy of corticosteroids such as delayed presentation, clinical severity, underlying anaemia, malnutrition, the antibiotics used, HIV infection or other unidentified differences between populations.

Recently, genetic factors were suggested to influence the patient's response to corticosteroids Brouwer Children in Malawi presented later and were more often comatose and malnourished, compared to children in Britain. Nevertheless, we stress the need for early diagnosis and treatment. Data from patients from five trials were included in the analysis HIV infection was confirmed or likely in Dexamethasone was not associated with a significant reduction in death of However, dexamethasone reduced hearing loss among survivors The differences between Malawi and the other clinical settings call into question the appropriateness of summary measures that combine the results, even if statistical tests of heterogeneity are deemed acceptable.

Treatment with adjunctive corticosteroids was not associated with harm. In order to establish with certainty whether or not dexamethasone has a place in the treatment of bacterial meningitis, a large multinational RCT in that subgroup would be necessary. Such a trial would need to include approximately 13, participants to show an odds ratio OR of 0. Three studies compared the prognosis of adult pneumococcal, meningococcal and Listeria monocytogenes meningitis between two nationwide prospective cohort studies; one was performed before and the other after the implementation of adjunctive dexamethasone Brouwer b ; Heckenberg b ; Koopmans No evidence of harm from dexamethasone was identified in studies on pneumococcal and meningococcal meningitis.

The beneficial effect of dexamethasone on pneumococcal meningitis was similar to that identified in the European Dexamethasone Study de Gans In a multivariate analysis bacterial genotype was found to be the main cause of the poorer prognosis. Dexamethasone was not associated with a change in mortality, hearing loss or sequelae in listerial meningitis. However, as adjunctive dexamethasone treatment was another major change between cohorts, it was suggested to discontinue dexamethasone when L monocytogenes is identified.

The study showed that over time mortality declined. This was attributed to the publication of the IDSA guideline of , which advised adjunctive dexamethasone for all suspected bacterial meningitis cases Castelblanco However, data on dexamethasone use were not available and therefore a causal relation could not be established. Both studies showed no effect of dexamethasone. However, in both studies the rationale to give or withhold dexamethasone was unclear and therefore confounding by indication patients with severe sickness get more medication, i.

Additional RCTs in neonatal meningitis are needed. We have read with interest the updated Review on Corticosteroids for acute bacterial meningitis. The figure for Analysis 3. These errors are not present in other figures for the quoted papers. The Thomas paper is misplaced in Analysis 3. Analysis 5. The Scarborough paper is from Malawi and correctly categorised as from a low income country.

The Bhaumik paper is categorised as from a high income country, but is in fact from India. The earlier text and all other analyses all place the Bhaumik paper in a low income country category. The Nguyen paper is categorised as from a high income country, but is in fact from Viet Nam.

The World Bank defines Viet Nam as a low middle income country. In fact the World Bank now defines India as a low middle income country. The only study clearly from high income countries is that by de Gans from Europe. The study which appears to demonstrate the greatest benefit from steroids on any hearing loss in adults is that by Nguyen in Viet Nam. In that paper the authors comment on the high proportion of cases of meningitis due to Streptococcus suis, and in Asia this is a recognised cause of deafness.

However S. This is another reason why placing the Nguyen study in the high income category is inappropriate. The distinction between adults and children varies by study and the Nguyen paper included individuals over 14 years of age. There is clear evidence for benefit from steroids in reducing deafness from Haemophilus influenzae meningitis in children Analysis 4.

Reference Okike IO et al. NG5 1PB. United Kingdom. I agree with the conflict of interest statement below: I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback. Analysis 3. We agree there are differences in epidemiology between studies, therefore we also performed a subgroup analysis for the major pathogens Analysis 4. For all other analyses we pooled all available data irrespective of epidemiology to find an overall effect.

In the applicability of the results it is good to realize the RCTs were performed in different time periods and multiple countries with variable epidemiology. Our assessment of trials included in the review that reported mortality and were deemed to be free of bias reveals an issue that we would like to highlight.

A sensitivity analysis that excludes the Scarborough et al. While one may argue that the upper bound of the confidence interval is close to the line of no difference, it is important to present the data this way as it is more reflective of the results of a pooling of less heterogeneous data and suggests that there may be benefit in an immunocompetent population.

In all four trials, selective outcome reporting is present. Specifically, none of the trials reported all adverse events AE. In addition, serious adverse events SAE data was not included in any of the trials. In two trials, AE were reported only if they were deemed by the investigator to be due to the study drug: the Scarborough et al. We respectfully suggest the authors of this review revisit the inclusion of the Scarborough et al.

In addition, a revision of the risk of bias table should be considered to provide readers with appropriate context with which to interpret the results, namely that AE were likely underreported in trials. References: 1. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. N Engl J Med. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.

The Lancet. Dexamethasone in adults with bacterial meningitis. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. Timothy S. Based on the chosen inclusion criteria we did not exclude studies from countries with high HIV positivity rates. To identify differences between areas of inclusion, which include HIV positivity but also e.

We agree there is lack of detail in the adverse events reporting in the included studies and thereby selective reporting. However, we feel this does not merit a full update of the review. May I comment on the statistical significance of the mortality benefit of corticosteroids when used for patients with Streptococcus pneumoniae pneumococcal meningitis as shown in Analysis 4. On this measure Analysis 4.

On this basis numerous guidelines around the world advocate the use of corticosteroids for meningitis in adults, particularly with St. We need to appreciate more about what underpins this calculation and I would make four points. Exclusion of this single study results in loss of statistical significance. Thus is there sufficient power to reach a clinically significant conclusion and do corticosteroids benefit the brain or protect against systemic complications?

References de Beek D, de Gans J. Dexamethasone and pneumococcal meningitis. Ann Int Med ; We would like to stress that we have included all results as they were from the studies at hand, of which the selection was based on the criteria described in the methods. Furthermore, in our opinion the sole focus on mortality in pneumococcal meningitis to decide to advise to for or against dexamethasone in bacterial meningitis patients is not justified.

The other analyses on hearing loss, severe hearing loss and neurological sequelae also show a consistent beneficial effect of corticosteroids without harm identified in any of the RCTs. The comparison to the MRC Crash study does not hold. In addition, the summary of findings table grades evidence as moderate and high quality. This section also appears to confuse quality with the risk of bias assessments. Authors should not make recommendations.

Also, this recommendation goes beyond the evidence for two reasons: the subgroup analyses Analysis 6. This should be declared as a conflict of interest, and assurance given that the data extraction and quality assessment of this study was independent. We did not identify the Cochrane Handbook recommendation referred to by Dr. Hine and Prof. Garner after checking the sections We agree this should have been mentioned as a conflict of interest and we have now changed the statement.

Matthijs C Brouwer independently extracted data and assessed quality. Protocol first published: Issue 3, Review first published: Issue 3, We also contacted manufacturers and researchers in the field DvdB. NWO Veni grant Brouwer; NWO Veni grant Matthijs C Brouwer: none known. Peter McIntyre: none known.

Kameshwar Prasad: none known. Diederik van de Beek is a primary author of one of the included trials de Gans National Center for Biotechnology Information , U. Published online Sep Box , AmsterdamNetherlands, DE. Diederik van de Beek, Email: ln. Author information Copyright and License information Disclaimer. Corresponding author. This article is an update of " Corticosteroids for acute bacterial meningitis. This article has been cited by other articles in PMC.

Abstract Background In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Objectives To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.

Selection criteria Randomised controlled trials RCTs of corticosteroids for acute bacterial meningitis. Data collection and analysis We scored RCTs for methodological quality. Main results We included 25 studies involving participants children and adults; 93 mixed population.

Authors' conclusions Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Background Acute bacterial meningitis is an infection of the meninges the system of membranes that envelops the brain and spinal cord , which often causes hearing loss.

Study characteristics The evidence is current to February Key results This review found that the corticosteroid dexamethasone did not significantly reduce the death rate Quality of the evidence Out of 25 studies, four were of high quality, 14 of medium quality and seven of low quality, leading to a moderate overall quality of evidence.

Summary of findings.

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Systemic side effects of steroid eye drops The evidence is current to February But the use of steroids in meningitis treatment is not without controversy. The differences between Malawi and the other clinical settings call into question the appropriateness of summary measures that combine the results, even if statistical tests of heterogeneity are deemed acceptable. Selection criteria Randomised controlled trials RCTs of corticosteroids for acute bacterial meningitis. Although some have suggested that steroid therapy be continued in bacterial meningitis caused by pathogens other than S balkan pharmaceuticals code10 we agree with authorities who recommend stopping if the causative agent proves to be other than pneumococcal.
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Why are steroids good for athletes The study showed that over time mortality declined. In five studies the method of sequence generation was unclear or not specified Bademosi ; Belsey ; Bennett ; Ciana ; British dragon oxanabol reviews of fuller Figure 2 ; Figure 1. Patients treated with corticosteroids had significantly lower rates of severe hearing loss 6. Corresponding author. Based on the available data, it seems most reasonable to give it for the first 4 days of therapy, although one pediatric study suggested that 2 days of therapy might provide the same benefit. Appendix 4. In order to establish with certainty whether or not dexamethasone has a place in the treatment of bacterial meningitis, a large multinational RCT in that subgroup would be necessary.
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Other complications occurred in similar proportions of the treatment and control groups. Corticosteroids prevented hearing loss in children: any hearing loss was found in of Out of participants with H influenzae meningitis, 87 died Corticosteroids protected against death in pneumococcal meningitis RR 0. For children with meningitis caused by H influenzae , hearing loss was significantly reduced by corticosteroids RR 0. For children with meningitis caused by bacteria other than H influenzae , no significant beneficial effect was seen RR 0.

Subgroup analysis on timing of corticosteroids before or with the first dose of antibiotics versus after the first dose of antibiotics showed similar results for mortality RR 0. We analysed studies in three categories of study quality according to the studies' 'Risk of bias' score Figure 1. Four studies including participants were categorised as high quality de Gans ; Molyneux ; Nguyen ; Scarborough , 14 studies with participants as medium quality DeLemos ; Kanra ; King ; Lebel a ; Lebel b ; Lebel ; Mathur ; Odio ; Peltola ; Qazi ; Sankar ; Sankar ; Schaad ; Thomas ; Wald , and seven studies including participants as low quality Bademosi ; Belsey ; Bennett ; Bhaumik ; Ciana ; Girgis ; Kilpi Severe hearing loss was reduced in studies of medium quality RR 0.

Results for other primary outcome measures did not differ from the initial analyses. Overall, corticosteroids significantly reduced the rate of hearing loss risk ratio RR 0. Subgroup analyses for age showed that in children with bacterial meningitis, corticosteroids prevented severe hearing loss RR 0. Subgroup analysis for causative organism showed that corticosteroids reduce severe hearing loss in children with meningitis due to H influenzae RR 0.

Subgroup analysis on S pneumoniae showed a favourable effect of corticosteroids on mortality RR 0. No effect on mortality was shown in H influenzae meningitis. Corticosteroids were protective against severe hearing loss RR 0. In this study physicians were not blinded to the treatment groups. Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics; of glucocorticoids, dexamethasone has superior penetration in the cerebrospinal fluid CSF and a longer half life Balis Therefore, dexamethasone is considered to be the corticosteroid of choice in bacterial meningitis.

Subgroup analyses for timing of corticosteroids before or with the first dose of antibiotics versus after the first dose of antibiotic showed no differences in efficacy of corticosteroids. In previous reports, administration of corticosteroids before or with the first dose of parenteral antibiotics seemed to be more effective than administration after the first dose of antibiotics King ; McIntyre A RCT involving adults with bacterial meningitis in European countries showed a beneficial effect of the corticosteroid dexamethasone on unfavourable outcome and mortality de Gans In this European study, dexamethasone or placebo was administered before or with the first dose of antibiotic de Gans The beneficial effect of dexamethasone on mortality was most apparent in patients with pneumococcal meningitis.

In a post hoc analysis of this study, the beneficial effect of dexamethasone on mortality in patients with pneumococcal meningitis was attributable to a reduction in systemic complications van de Beek a. Although speculative and not supported by clinical data, one implication of this finding might be that the effect of dexamethasone is not restricted to the first hours after administration van de Beek b. Data from patients from five trials were included and the aim of this analysis was to establish whether any subgroups of patients with acute bacterial meningitis might benefit from adjunctive dexamethasone.

There were no differences in efficacy of adjunctive dexamethasone with regard to the timing of corticosteroids. Hence, there is a time period beyond which corticosteroid loses its effectiveness after the first parenteral administration of an antibiotic agent but this time interval has not been clearly defined. On the basis of the available evidence, dexamethasone should be preferably started before or with the first dose of antibiotic therapy.

The study included of evaluable participants surviving the initial trial period. The authors conclude that the beneficial effect of dexamethasone that is obtained in the acute phase of the disease remains for years. In children with acute bacterial meningitis, corticosteroids reduced hearing loss from However, as conclusive evidence is lacking for this subgroup, administration of corticosteroids to children with meningitis due to bacteria other than H influenzae remains controversial.

Only one study in this analysis involved children with neonatal meningitis and showed a beneficial effect of corticosteroids on outcomes Mathur Additional RCTs evaluating corticosteroids in neonatal meningitis need to be performed before definitive conclusions can be drawn on the role of dexamethasone treatment in neonatal meningitis. The use of steroids was associated with fewer cases of persistent fever and more cases of recurrent fever, but not with serious adverse events. Therapeutic failures have been described in adults treated with standard doses of vancomycin and adjunctive dexamethasone Viladrich However, two studies showed with repeated lumbar punctures that, in both adults and children, treatment with dexamethasone did not reduce vancomycin levels in the CSF Klugman ; Ricard Although these results are reassuring, patients with pneumococcal meningitis who are treated with vancomycin and dexamethasone should still be carefully observed throughout therapy van de Beek a.

In adults who survive acute bacterial meningitis, cognitive impairment occurs frequently van de Beek ; van de Beek a. As corticosteroids may potentiate ischaemic injury to neurons Sapolsky , it is important to know whether corticosteroids have beneficial effects on hearing loss and mortality but worsen cerebral cortical functioning van de Beek b. Neuropsychological outcome was evaluated in patients included in the European Dexamethasone Study who survived pneumococcal or meningococcal meningitis Weisfelt For the analysis on severe hearing loss, significant heterogeneity between trials of high, medium and low quality was found.

When this study was left out a trend towards benefit of dexamethasone on any hearing loss was found Molyneux Several biases may have diminished the reliability of our results. The first confounding factor is selection bias. For patients admitted in a late state of disease, adjuvant corticosteroids are less protective and might even be harmful Prasad Inclusion of such patients might again lead to an underestimation of the treatment effect. A second bias is introduced when participants are withdrawn Prasad ; Qazi A total of participants were withdrawn after the randomisation process, often for unknown reasons.

Reasons for withdrawal include ineligibility according to the trial criteria or inability to complete the treatment protocol Prasad Withdrawals on the grounds on ineligibility may have been influenced by knowledge of outcome; if so, this would advantage the corticosteroid regimen. A third bias is introduced by competing risks.

The comparisons of hearing loss and neurologic sequelae other than hearing loss were made excluding all participants who died. Competing risks in this analysis will lead to an underestimation of the treatment effect of corticosteroids.

Finally, the included studies were heterogeneous with respect to the study protocols. The first study was published in Bennett , the last in Mathur Several different study interventions were used. Therefore, study population effect sizes were calculated as risk ratios. However, other countries that were included had only slightly higher HDIs at the time of inclusion Girgis , Egypt 0.

According to the classification of study quality used, most of these studies were of similar quality to those that were included. There may be several reasons for the difference in efficacy of corticosteroids such as delayed presentation, clinical severity, underlying anaemia, malnutrition, the antibiotics used, HIV infection or other unidentified differences between populations.

Recently, genetic factors were suggested to influence the patient's response to corticosteroids Brouwer Children in Malawi presented later and were more often comatose and malnourished, compared to children in Britain. Nevertheless, we stress the need for early diagnosis and treatment. Data from patients from five trials were included in the analysis HIV infection was confirmed or likely in Dexamethasone was not associated with a significant reduction in death of However, dexamethasone reduced hearing loss among survivors The differences between Malawi and the other clinical settings call into question the appropriateness of summary measures that combine the results, even if statistical tests of heterogeneity are deemed acceptable.

Treatment with adjunctive corticosteroids was not associated with harm. In order to establish with certainty whether or not dexamethasone has a place in the treatment of bacterial meningitis, a large multinational RCT in that subgroup would be necessary. Such a trial would need to include approximately 13, participants to show an odds ratio OR of 0. Three studies compared the prognosis of adult pneumococcal, meningococcal and Listeria monocytogenes meningitis between two nationwide prospective cohort studies; one was performed before and the other after the implementation of adjunctive dexamethasone Brouwer b ; Heckenberg b ; Koopmans No evidence of harm from dexamethasone was identified in studies on pneumococcal and meningococcal meningitis.

The beneficial effect of dexamethasone on pneumococcal meningitis was similar to that identified in the European Dexamethasone Study de Gans In a multivariate analysis bacterial genotype was found to be the main cause of the poorer prognosis. Dexamethasone was not associated with a change in mortality, hearing loss or sequelae in listerial meningitis. However, as adjunctive dexamethasone treatment was another major change between cohorts, it was suggested to discontinue dexamethasone when L monocytogenes is identified.

The study showed that over time mortality declined. This was attributed to the publication of the IDSA guideline of , which advised adjunctive dexamethasone for all suspected bacterial meningitis cases Castelblanco However, data on dexamethasone use were not available and therefore a causal relation could not be established. Both studies showed no effect of dexamethasone. However, in both studies the rationale to give or withhold dexamethasone was unclear and therefore confounding by indication patients with severe sickness get more medication, i.

Additional RCTs in neonatal meningitis are needed. We have read with interest the updated Review on Corticosteroids for acute bacterial meningitis. The figure for Analysis 3. These errors are not present in other figures for the quoted papers.

The Thomas paper is misplaced in Analysis 3. Analysis 5. The Scarborough paper is from Malawi and correctly categorised as from a low income country. The Bhaumik paper is categorised as from a high income country, but is in fact from India. The earlier text and all other analyses all place the Bhaumik paper in a low income country category. The Nguyen paper is categorised as from a high income country, but is in fact from Viet Nam.

The World Bank defines Viet Nam as a low middle income country. In fact the World Bank now defines India as a low middle income country. The only study clearly from high income countries is that by de Gans from Europe. The study which appears to demonstrate the greatest benefit from steroids on any hearing loss in adults is that by Nguyen in Viet Nam.

In that paper the authors comment on the high proportion of cases of meningitis due to Streptococcus suis, and in Asia this is a recognised cause of deafness. However S. This is another reason why placing the Nguyen study in the high income category is inappropriate. The distinction between adults and children varies by study and the Nguyen paper included individuals over 14 years of age.

There is clear evidence for benefit from steroids in reducing deafness from Haemophilus influenzae meningitis in children Analysis 4. Reference Okike IO et al. NG5 1PB. United Kingdom. I agree with the conflict of interest statement below: I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback. Analysis 3. We agree there are differences in epidemiology between studies, therefore we also performed a subgroup analysis for the major pathogens Analysis 4.

For all other analyses we pooled all available data irrespective of epidemiology to find an overall effect. In the applicability of the results it is good to realize the RCTs were performed in different time periods and multiple countries with variable epidemiology. Our assessment of trials included in the review that reported mortality and were deemed to be free of bias reveals an issue that we would like to highlight.

A sensitivity analysis that excludes the Scarborough et al. While one may argue that the upper bound of the confidence interval is close to the line of no difference, it is important to present the data this way as it is more reflective of the results of a pooling of less heterogeneous data and suggests that there may be benefit in an immunocompetent population.

In all four trials, selective outcome reporting is present. Specifically, none of the trials reported all adverse events AE. In addition, serious adverse events SAE data was not included in any of the trials. In two trials, AE were reported only if they were deemed by the investigator to be due to the study drug: the Scarborough et al.

We respectfully suggest the authors of this review revisit the inclusion of the Scarborough et al. In addition, a revision of the risk of bias table should be considered to provide readers with appropriate context with which to interpret the results, namely that AE were likely underreported in trials. References: 1. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. N Engl J Med. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.

The Lancet. Dexamethasone in adults with bacterial meningitis. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. Timothy S. Based on the chosen inclusion criteria we did not exclude studies from countries with high HIV positivity rates.

To identify differences between areas of inclusion, which include HIV positivity but also e. We agree there is lack of detail in the adverse events reporting in the included studies and thereby selective reporting. However, we feel this does not merit a full update of the review.

May I comment on the statistical significance of the mortality benefit of corticosteroids when used for patients with Streptococcus pneumoniae pneumococcal meningitis as shown in Analysis 4. On this measure Analysis 4. On this basis numerous guidelines around the world advocate the use of corticosteroids for meningitis in adults, particularly with St.

We need to appreciate more about what underpins this calculation and I would make four points. Exclusion of this single study results in loss of statistical significance. Thus is there sufficient power to reach a clinically significant conclusion and do corticosteroids benefit the brain or protect against systemic complications? References de Beek D, de Gans J. Dexamethasone and pneumococcal meningitis.

Ann Int Med ; We would like to stress that we have included all results as they were from the studies at hand, of which the selection was based on the criteria described in the methods. Furthermore, in our opinion the sole focus on mortality in pneumococcal meningitis to decide to advise to for or against dexamethasone in bacterial meningitis patients is not justified.

The other analyses on hearing loss, severe hearing loss and neurological sequelae also show a consistent beneficial effect of corticosteroids without harm identified in any of the RCTs. The comparison to the MRC Crash study does not hold. In addition, the summary of findings table grades evidence as moderate and high quality. This section also appears to confuse quality with the risk of bias assessments. Authors should not make recommendations. Also, this recommendation goes beyond the evidence for two reasons: the subgroup analyses Analysis 6.

This should be declared as a conflict of interest, and assurance given that the data extraction and quality assessment of this study was independent. We did not identify the Cochrane Handbook recommendation referred to by Dr.

Hine and Prof. Garner after checking the sections We agree this should have been mentioned as a conflict of interest and we have now changed the statement. Matthijs C Brouwer independently extracted data and assessed quality. Protocol first published: Issue 3, Review first published: Issue 3, We also contacted manufacturers and researchers in the field DvdB.

NWO Veni grant Brouwer; NWO Veni grant Matthijs C Brouwer: none known. Peter McIntyre: none known. Kameshwar Prasad: none known. Diederik van de Beek is a primary author of one of the included trials de Gans National Center for Biotechnology Information , U. Published online Sep Box , AmsterdamNetherlands, DE. Diederik van de Beek, Email: ln. Author information Copyright and License information Disclaimer. Corresponding author. This article is an update of " Corticosteroids for acute bacterial meningitis.

This article has been cited by other articles in PMC. Abstract Background In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Objectives To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.

Selection criteria Randomised controlled trials RCTs of corticosteroids for acute bacterial meningitis. Data collection and analysis We scored RCTs for methodological quality. Main results We included 25 studies involving participants children and adults; 93 mixed population. Authors' conclusions Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Background Acute bacterial meningitis is an infection of the meninges the system of membranes that envelops the brain and spinal cord , which often causes hearing loss.

Study characteristics The evidence is current to February Key results This review found that the corticosteroid dexamethasone did not significantly reduce the death rate Quality of the evidence Out of 25 studies, four were of high quality, 14 of medium quality and seven of low quality, leading to a moderate overall quality of evidence.

Summary of findings. Background Description of the condition Bacterial meningitis is a severe infection of the meninges the membrane lining of the brain and spinal cord that is associated with high mortality and morbidity rates despite optimal antibiotic therapy and advances in critical care Baraff ; Bohr ; Brouwer c ; van de Beek ; van de Beek b ; van de Beek b. Description of the intervention Intravenously or orally administered corticosteroids, such as prednisolone, hydrocortisone and dexamethasone, are given before, with or after antibiotic treatment for suspected or proven bacterial meningitis.

How the intervention might work In experimental animal studies, the outcome of meningitis worsens with increasing severity of the inflammatory process in the subarachnoidal space Scheld ; Tauber Why it is important to do this review In the s two randomised controlled trials RCTs evaluated the effect of corticosteroids in patients with bacterial meningitis Bennett ; DeLemos Types of participants Participants of any age and in any clinical condition. Primary outcomes Mortality Hearing loss Neurological sequelae Hearing loss was defined as severe when there was bilateral hearing loss greater than 60 dB or requiring bilateral hearing aids.

Searching other resources Besides the electronic search we identified relevant trials by searching references listed in published studies, handsearching congress abstracts, personal communication with researchers and experts in the field and from literature lists of pharmaceutical companies. Data collection and analysis Selection of studies Two review authors MD, DvdB independently screened the search results and retrieved the full articles of all potentially relevant trials.

Assessment of risk of bias in included studies For each study we completed a 'Risk of bias' table, scoring for adequacy of sequence generation, allocation concealment, blinding, if incomplete data were addressed, selective reporting and other sources of bias Higgins Measures of treatment effect All outcome measures were dichotomous.

Dealing with missing data We contacted the corresponding publication author in the case of unclear or missing data. Assessment of reporting biases We conducted visual inspection of the funnel plot of the studies for any obvious asymmetry that could indicate publication bias. Data synthesis We analysed the data using Review Manager 5. Results Description of studies Results of the search Since the first publication of this review we have retrieved a total of records.

Excluded studies We excluded 16 trials Characteristics of excluded studies. Risk of bias in included studies Summary of general risk of bias Four of 25 studies were free of bias, whereas the other 21 had one or more biases. Open in a separate window. Allocation The sequence generation for participant allocation was adequate in 20 studies.

Incomplete outcome data Missing data were addressed in 16 studies and were not addressed in eight Bademosi ; Belsey ; Bennett ; Bhaumik ; Girgis ; Kanra ; Schaad ; Thomas Analysis Comparison 1 All patients, Outcome 1 Mortality. Analysis Comparison 1 All patients, Outcome 2 Severe hearing loss. Analysis Comparison 1 All patients, Outcome 3 Any hearing loss. Analysis Comparison 1 All patients, Outcome 6 Adverse events.

Other potential sources of bias In 12 studies differences in baseline and clinical characteristics between treatment and control groups influenced comparability of groups Bademosi ; Belsey ; Bhaumik ; DeLemos ; Kanra ; Kilpi ; Lebel ; Mathur ; Peltola ; Sankar ; Thomas , indicating either insufficient sample size to equal out the random differences between randomisation arms or a selection bias.

Effects of interventions See: Table 1 Summary of findings for the main comparison Summary of findings table. CI: confidence interval; RR: risk ratio; OR: odds ratio GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Primary outcomes 1. Forest plot of comparison: 1 All patients, outcome: 1. Secondary outcome 1. Adverse events Adverse events were recorded in 20 studies: 16 evaluated gastrointestinal haemorrhage, 12 recurrent fever, six reactive arthritis, five herpes zoster, three persistent fever and one fungal infections Belsey ; Bennett ; Bhaumik ; de Gans ; Kanra ; Kilpi ; King ; Lebel a ; Lebel b ; Lebel ; Mathur ; Nguyen ; Odio ; Peltola ; Qazi ; Sankar ; Scarborough ; Schaad ; Thomas ; Wald Analysis 1.

Analysis Comparison 2 Children, Outcome 1 Mortality. Analysis Comparison 2 Children, Outcome 2 Severe hearing loss. Analysis Comparison 2 Children, Outcome 3 Any hearing loss. Analysis Comparison 3 Adults, Outcome 1 Mortality. Analysis Comparison 3 Adults, Outcome 2 Any hearing loss. Analysis Comparison 4 Causative species, Outcome 1 Mortality. Analysis Comparison 5 Income of countries, Outcome 3 Any hearing loss.

Analysis Comparison 5 Income of countries, Outcome 10 Any hearing loss adults. Analysis Comparison 6 Timing of steroids, Outcome 1 Mortality. Analysis Comparison 6 Timing of steroids, Outcome 2 Severe hearing loss. Analysis Comparison 6 Timing of steroids, Outcome 3 Any hearing loss. Analysis Comparison 7 Study quality, Outcome 1 Mortality. Analysis Comparison 7 Study quality, Outcome 2 Severe hearing loss.

Analysis Comparison 7 Study quality, Outcome 3 Any hearing loss. Applicability of evidence In children with acute bacterial meningitis, corticosteroids reduced hearing loss from Potential biases in the review process Several biases may have diminished the reliability of our results. Authors' conclusions Implications for practice.

Implications for research. Feedback Corticosteroids for acute bacterial meningitis, 3 October Summary We have read with interest the updated Review on Corticosteroids for acute bacterial meningitis. Reply Analysis 3. Contributors Matthijs Brouwer Diederik van de Beek. Tejani, BScPharm PharmD I agree with the conflict of interest statement below: I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

Reply Based on the chosen inclusion criteria we did not exclude studies from countries with high HIV positivity rates. Corticosteroids for acute bacterial meningitis, 11 September Summary May I comment on the statistical significance of the mortality benefit of corticosteroids when used for patients with Streptococcus pneumoniae pneumococcal meningitis as shown in Analysis 4. Contributors Matthijs Brouwer Diederik van der Beek. We would suggest that this review is updated to ensure transparency.

Reply We did not identify the Cochrane Handbook recommendation referred to by Dr. What's new Date Event Description 8 November Feedback has been incorporated Authors responded to feedback comments. History Protocol first published: Issue 3, Review first published: Issue 3, Date Event Description 20 August Feedback has been incorporated Feedback comment added to the review. Our conclusions remain unchanged. We did not identify any new trials for inclusion.

Appendices Appendix 1. Appendix 2. We performed the search without any language or publication restrictions. Appendix 3. Appendix 4. Appendix 5. Appendix 6. Appendix 7. Notes Edited no change to conclusions , comment added to review. Data and analyses Comparison 1 All patients.

Outcome or subgroup title No. Comparison 2 Children. Comparison 3 Adults. Comparison 4 Causative species. Comparison 5 Income of countries. Comparison 6 Timing of steroids. Comparison 7 Study quality. Characteristics of studies Characteristics of included studies [ordered by study ID] Bademosi Belsey Bennett Bhaumik Ciana DeLemos Girgis Kanra Kilpi Unevenly distributed between randomisation arms.

King In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.

We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.

We included 25 studies involving participants children and adults; 93 mixed population. Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. There was insufficient evidence that corticosteroids caused a reduction in mortality overall However they caused lower rates of severe hearing loss RR 0. Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae S pneumoniae meningitis RR 0.

Corticosteroids reduced severe hearing loss in children with H influenzae meningitis RR 0. In high-income countries, corticosteroids reduced severe hearing loss RR 0. Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies. Corticosteroid treatment was associated with an increase in recurrent fever RR 1. Background Acute bacterial meningitis is an infection of the meninges the system of membranes that envelops the brain and spinal cord , which often causes hearing loss.

We wanted to discover whether use of corticosteroids was better of worse than placebo. Study characteristics The evidence is current to February Key results This review found that the corticosteroid dexamethasone did not significantly reduce the death rate Quality of the evidence Out of 25 studies, four were of high quality, 14 of medium quality and seven of low quality, leading to a moderate overall quality of evidence.

Authors' conclusions:. Search strategy:. Selection criteria:.