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Corticosteroids for acute bacterial meningitis

  1. Matthijs C Brouwer1,
  2. Peter McIntyre2,
  3. Kameshwar Prasad3,
  4. Diederik van de Beek1,*

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 4 JUN 2013

Assessed as up-to-date: 18 JAN 2013

DOI: 10.1002/14651858.CD004405.pub4


How to Cite

Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD004405. DOI: 10.1002/14651858.CD004405.pub4.

Author Information

  1. 1

    Academic Medical Center University of Amsterdam, Department of Neurology, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, Netherlands

  2. 2

    Children's Hospital at Westmead and University of Sydney, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, Sydney, NSW, Australia

  3. 3

    All India Institute of Medical Sciences, Department of Neurology, New Delhi, India

*Diederik van de Beek, Department of Neurology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center University of Amsterdam, P.O. Box 22660, Amsterdam, 1100 DE, Netherlands. D.vandeBeek@amc.uva.nl.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 4 JUN 2013

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Characteristics of included studies [ordered by study ID]
Bademosi 1979

MethodsRandomised, unblinded


Participants10 to 59 years; bacteriologically proven pneumococcal meningitis


InterventionsHydrocortisone, 100 mg; followed by prednisolone 60 mg/d, 14 d; before or with antibiotics (AB)


OutcomesMortality


NotesAB - Sulf/pen, mortality 44%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation procedure is not specified

Allocation concealment (selection bias)High riskThe treatment allocation is not concealed

Blinding (performance bias and detection bias)
All outcomes
High riskThe study is not blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)Unclear riskNo information provided

Other biasHigh riskLimited data presented; unevenly distributed severity of disease

Belsey 1969

MethodsRandomised, double-blind


Participants0 to 17 years; purulent meningitis


InterventionsDXM 1.2 mg/m2/d, 4 d; timing unclear


OutcomesMortality, hearing loss, adverse events (herpes zoster infections)


NotesAB - Chlor/sulf/pen, mortality 3%
Other - matching of patients and controls in 48 categories


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation procedure not specified

Allocation concealment (selection bias)Unclear riskNo information on allocation concealment is provided

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blinded trial

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High risk16 randomised patients that could not be matched were not included; patients dying < 18 hours of hospitalisation were excluded from the analysis. No intention-to-treat analysis

Other biasHigh riskUnevenly distributed severity of disease at admission (control group worse)

Bennett 1963

MethodsRandomised, double-blind


ParticipantsAll ages; life-threatening infectious diseases, subgroup meningitis


InterventionsHydrocortisone scheme, 7 d; after AB


OutcomesMortality


NotesAB - not specified, mortality 45%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation procedure not specified

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis for suspected bacterial meningitis patients. Selection of culture-proven bacterial meningitis patients from a large cohort of severely ill patients

Other biasUnclear riskBaseline characteristics and treatment specifications of DXM and control groups are not reported

Bhaumik 1998

MethodsRandomised, unblinded


Participants12 to 75 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 16 mg/day, 4 d, plus 3 d scheme; after AB


OutcomesMortality, neurological sequelae, adverse events (not specified)


NotesAB - pen/chlor or ceph, mortality 13%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised table chart

Allocation concealment (selection bias)High riskThe treatment allocation was not concealed

Blinding (performance bias and detection bias)
All outcomes
High riskThe study is not blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)Unclear riskNo intention-to-treat analysis

Other biasHigh riskUnevenly distributed baseline and clinical characteristics

Ciana 1995

MethodsRandomised, unblinded


Participants2 months to 6 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.4 mg/kg, 3 d; timing unclear


OutcomesMortality, neurological sequelae, adverse events (recurrent fever)


NotesAB - ampi/chlor, mortality 28%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation procedure not specified

Allocation concealment (selection bias)High riskThe treatment allocation was not concealed

Blinding (performance bias and detection bias)
All outcomes
High riskThe study is not blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskPatient retrospectively excluded because of different diagnosis; high number of comatose patients compared to other trials. No intention-to-treat analysis

Other biasUnclear riskLimited clinical data available

de Gans 2002

MethodsRandomised, double-blind


ParticipantsOlder than 16 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 40 mg/d, 4 d; before or with AB


OutcomesMortality, neurological sequelae, adverse events (herpes zoster/fungal infections, gastrointestinal bleeding, hyperglycaemia)


NotesAB - various, mortality 11%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list, block size 6

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up

Selective reporting (reporting bias)Low riskInclusion chart provided. Intention-to-treat analysis

Other biasLow riskNo indication of other bias

DeLemos 1969

MethodsRandomised, double-blind


Participants1 month to 17 years; diagnosis bacterial meningitis


InterventionsMethylprednisolone 120 mg/d, 3 d; after AB


OutcomesMortality


NotesAB - chlor/sulf/pen, mortality 3%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised, block size 12

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskAntibiotic pretreatment unevenly distributed between randomisation arms

Girgis 1989

MethodsRandomised, unblinded


Participants3 months to 70 years; diagnosis bacterial meningitis


InterventionsDXM 16 to 24 mg/d, 4 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae


NotesAB - chlor/ampi, mortality 15%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPre-designed randomisation chart

Allocation concealment (selection bias)High riskThe treatment allocation was not concealed

Blinding (performance bias and detection bias)
All outcomes
High riskStudy was not blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskThe very high number of comatose patients compared to other studies suggests a selection bias

Kanra 1995

MethodsRandomised, double-blind


Participants2 to 6 years; bacteriologically proven pneumococcal meningitis


InterventionsDXM 0.6 mg/kg/d, 4 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (recurrent fever)


NotesAB - sulf/ampi, mortality 5%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskStudy was double-blind

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis; selection of pneumococcal meningitis patients

Other biasHigh riskUnevenly distributed severity of disease (Glasgow Coma Scale) at admission (control group better)

Kilpi 1995

MethodsRandomised, unblinded


Participants3 months to 15 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 1.5 mg/kg/d, 3 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding)


NotesAB - ceph, mortality 2%
Other - trial also evaluated adjunctive glycerol and combined adjunctive glycerol and DXM therapy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list of random therapy assignments

Allocation concealment (selection bias)High riskThe treatment allocation was not concealed

Blinding (performance bias and detection bias)
All outcomes
High riskStudy was not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskHigh number of pre-treated patients compared to other studies. Unevenly distributed between randomisation arms

King 1994

MethodsRandomised, double-blind


Participants1 month to 13 years; suspected bacterial meningitis with CSF or blood criterion; also patients with suspected bacterial meningitis who were too unstable for lumbar puncture


InterventionsDXM 0.6 mg/kg/d, 4 d; after AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, persistent fever, recurrent fever)


NotesAB - various, mortality 1%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStratified computer-generated randomisation

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis; more patients were excluded in the dexamethasone group because of final diagnosis other than bacterial meningitis

Other biasUnclear riskInsufficient information to determine other bias

Lebel 1988a

MethodsRandomised, double-blind


Participants2 months to 16 years; suspected or proven bacterial meningitis


InterventionsDXM 0.6 mg/kg/d, 4 d; after AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, recurrent fever, arthritis)


NotesAB - ceph, mortality 2%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasUnclear riskInsufficient information to determine other bias

Lebel 1988b

MethodsRandomised, double-blind


Participants2 months to 16 years; suspected or proven bacterial meningitis


InterventionsDXM 0.6 mg/kg/d, 4 d; after AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, recurrent fever, arthritis)


NotesAB - ceph, mortality 2%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasUnclear riskInsufficient information to determine other bias

Lebel 1989

MethodsRandomised, double-blind


Participants2 months to 16 years; suspected or proven bacterial meningitis


InterventionsDXM 0.6 mg/kg/d, 4 d; after AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, recurrent fever, arthritis)


NotesAB - ceph, mortality 2%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskUnevenly distributed number of antimicrobial resistance rates between treatment groups (control group worse)

Mathur 2013

MethodsRandomised, unblinded


ParticipantsNeonates (not defined)


InterventionsDXM 0.6 mg/kg/d, 2 days, with AB


OutcomesMortality, hearing loss, CSF parameters of inflammation at 24 h, disease severity


NotesAB - ceph/amikacine + meropenem in severe cases, mortality 26%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskWeb-based randomisation

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskData complete, no patients lost to follow-up or discontinued treatment

Selective reporting (reporting bias)Low riskData complete, no patients lost to follow-up or discontinued treatment

Other biasHigh riskDifferences in causative bacteria and culture-positive cases between treatment groups

Molyneux 2002

MethodsRandomised, double-blind


Participants2 months to 13 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.8 mg/kg/d, 2 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae


NotesAB - pen/chlor, mortality 31%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)Low riskIntention-to-treat analysis

Other biasLow riskNo indication of other bias

Nguyen 2007

MethodsRandomised, double-blind


ParticipantsOlder than 14 years; culture-proven bacterial meningitis or suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.8 mg/kg/d, 4 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (herpes zoster infection, gastrointestinal bleeding)


NotesAB - various; mortality 11%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list, block size 100

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)Low riskIntention-to-treat analysis

Other biasLow riskNo indication of other bias

Odio 1991

MethodsRandomised, double-blind


Participants6 weeks to 16 years; culture-proven bacterial meningitis or suspected bacterial meningitis with CSF inflammation


InterventionsDXM 0.6 mg/kg/d, 4 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, persistent fever, recurrent fever, arthritis)


NotesAB - ceph, mortality - 2%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasUnclear riskInsufficient information to determine other bias

Peltola 2007

MethodsRandomised, double-blind


Participants2 months to 16 years; proven or suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.6 mg/kg/d, 4 d; before or with AB


OutcomesMortality, neurological sequelae, hearing loss, adverse events (gastrointestinal bleeding, recurrent fever)


NotesAB - ceph, mortality 15%

Other - trial also evaluated adjunctive glycerol and combined adjunctive glycerol and DXM therapy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation list, block size 24

Allocation concealment (selection bias)Unclear riskPartial allocation concealment: 2 hospitals did not allow double placebo treatment

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)Low riskIntention-to-treat analysis

Other biasUnclear riskUnevenly distributed antibiotic pretreatment between randomisation arms

Qazi 1996

MethodsRandomised, double-blind


Participants2 months to 12 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.6 mg/kg/d, 4 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding)


NotesAB - ampi/chlor, mortality 19%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskHigh rate of culture-negative patients. High mortality but low rate of hearing loss. More changes in antibiotic therapy in control population

Sankar 2007

MethodsRandomised, double-blind


Participants2 months to 12 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.9 mg/kg, 2 d; timing unclear


OutcomesMortality, neurological sequelae, adverse events (gastrointestinal bleeding)


NotesAB - ceph, mortality 4%

Other - trial also evaluated adjunctive glycerol and combined adjunctive glycerol and DXM therapy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)Low riskIntention-to-treat analysis

Other biasUnclear riskOnly 1 patient with positive culture in DXM randomisation arm. Unevenly distributed numbers in randomisation arms. Large differences in baseline characteristics between randomisation arms

Scarborough 2007

MethodsRandomised, double-blind


ParticipantsOlder than 15 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 32 mg/day, 4 d; before or with AB


OutcomesMortality, neurological sequelae, hearing loss, adverse events (herpes zoster infection, gastrointestinal bleeding, recurrent fever)


NotesAB - ceph, mortality 54%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list, block size 8

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)Low riskIntention-to-treat analysis

Other biasLow riskNo indication of other bias

Schaad 1993

MethodsRandomised, double-blind


Participants3 months to 16 years; suspected or proven bacterial


InterventionsDXM 0.8 mg/kg/d, 2 d; before or with AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, recurrent fever, persistent fever, arthritis)


NotesAB - ceph, mortality 0%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasUnclear riskInsufficient information to determine other bias

Thomas 1999

MethodsRandomised, double-blind


Participants17 to 99 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 40 mg/d, 3 d; after AB


OutcomesMortality, neurological sequelae, adverse events (herpes zoster infection, gastrointestinal bleeding)


NotesAB - amox, mortality 13%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStratified, equilibrated randomisation list

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
High riskIncomplete outcome data not addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasHigh riskLimited baseline and clinical characteristics. Age of participants unevenly distributed between randomisation arms

Wald 1995

MethodsRandomised, double-blind


Participants2 months to 12 years; suspected bacterial meningitis with CSF criteria


InterventionsDXM 0.6 mg/kg/d, 4 d; after AB


OutcomesMortality, hearing loss, neurological sequelae, adverse events (gastrointestinal bleeding, recurrent fever, arthritis)


NotesAB - cephalosporin, mortality - 1%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list, block size 10

Allocation concealment (selection bias)Low riskAllocation was concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskThe study was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskIncomplete outcome data addressed

Selective reporting (reporting bias)High riskNo intention-to-treat analysis

Other biasUnclear riskDistribution of resistant bacterial strains (23 out of 143 strains) between randomisation arms is not reported

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ayaz 2008Inadequate sequence generation

Baldy 1986Inadequate sequence generation

Daoud 1999Inadequate sequence generation

Farina 1995Not enough data for inclusion (abstract only)

Gijwani 2002Inadequate sequence generation

Gupta 1996Inadequate sequence generation

Jensen 1969Inadequate sequence generation

Lepper 1959Inadequate sequence generation

Marguet 1993No randomisation

Ozen 2006No randomisation

Passos 1979Inadequate sequence generation

Peltola 2004Not enough data for inclusion

Shembesh 1997Inadequate sequence generation

Singhi 2008Data previously published (Sankar 2007)

Syrogiannopoulos 1994No placebo group, compared 2-day 4-day regimen of dexamethasone

Tolaj 2010No randomisation

 
Comparison 1. All patients

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality254121Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.80, 1.01]

 2 Severe hearing loss172437Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.51, 0.88]

 3 Any hearing loss202785Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.63, 0.87]

 4 Short-term neurological sequelae131756Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.69, 1.00]

 5 Long-term neurological sequelae131706Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.74, 1.10]

 6 Adverse events20Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 Gastrointestinal bleeding
162560Risk Ratio (M-H, Fixed, 95% CI)1.45 [0.86, 2.45]

    6.2 Herpes zoster infection
61432Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.86, 1.37]

    6.3 Persistent fever
3316Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.12, 0.70]

    6.4 Recurrent fever
121723Risk Ratio (M-H, Fixed, 95% CI)1.27 [1.09, 1.47]

    6.5 Fungal infection
1301Risk Ratio (M-H, Fixed, 95% CI)1.83 [0.56, 5.96]

    6.6 Arthritis
6618Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.27, 1.53]

 
Comparison 2. Children

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality182511Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.74, 1.07]

 2 Severe hearing loss141524Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.49, 0.91]

 3 Any hearing loss161961Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.61, 0.86]

 
Comparison 3. Adults

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality71517Risk Ratio (M-H, Random, 95% CI)0.74 [0.53, 1.05]

 2 Any hearing loss4844Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.56, 0.98]

 3 Short-term neurological sequelae4542Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.51, 1.01]

 
Comparison 4. Causative species

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality18Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Haemophilus influenzae
11825Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.53, 1.09]

    1.2 Streptococcus pneumoniae
171132Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.72, 0.98]

    1.3 Neisseria meningitidis
13618Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.35, 1.46]

 2 Severe hearing loss in children - non-Haemophilus influenzae species13860Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.65, 1.39]

 3 Severe hearing loss in children - Haemophilus influenzae10756Risk Ratio (M-H, Fixed, 95% CI)0.34 [0.20, 0.59]

 
Comparison 5. Income of countries

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality - all patients254121Risk Ratio (IV, Random, 95% CI)0.88 [0.75, 1.03]

    1.1 Low-income countries
91873Risk Ratio (IV, Random, 95% CI)0.87 [0.67, 1.15]

    1.2 High-income countries
162248Risk Ratio (IV, Random, 95% CI)0.81 [0.63, 1.05]

 2 Severe hearing loss - all patients172445Risk Ratio (IV, Fixed, 95% CI)0.74 [0.58, 0.94]

    2.1 Low-income countries
5944Risk Ratio (IV, Fixed, 95% CI)0.99 [0.72, 1.38]

    2.2 High-income countries
121501Risk Ratio (IV, Fixed, 95% CI)0.51 [0.35, 0.73]

 3 Any hearing loss202805Risk Ratio (IV, Fixed, 95% CI)0.79 [0.69, 0.89]

    3.1 Low-income countries
71051Risk Ratio (IV, Fixed, 95% CI)0.89 [0.76, 1.04]

    3.2 High-income countries
131754Risk Ratio (IV, Fixed, 95% CI)0.58 [0.45, 0.73]

 4 Short-term neurological sequelae - all patients141814Risk Ratio (IV, Fixed, 95% CI)0.84 [0.70, 1.02]

    4.1 Low-income countries
5735Risk Ratio (IV, Fixed, 95% CI)1.03 [0.81, 1.31]

    4.2 High-income countries
91079Risk Ratio (IV, Fixed, 95% CI)0.64 [0.48, 0.85]

 5 Mortality - children172486Risk Ratio (IV, Fixed, 95% CI)0.92 [0.77, 1.11]

    5.1 Low-income countries
51119Risk Ratio (IV, Fixed, 95% CI)0.91 [0.75, 1.12]

    5.2 High-income countries
121367Risk Ratio (IV, Fixed, 95% CI)0.96 [0.61, 1.50]

 6 Severe hearing loss - children141531Risk Ratio (IV, Fixed, 95% CI)0.74 [0.56, 0.98]

    6.1 Low-income countries
3387Risk Ratio (IV, Fixed, 95% CI)1.00 [0.69, 1.47]

    6.2 High-income countries
111144Risk Ratio (IV, Fixed, 95% CI)0.52 [0.35, 0.78]

 7 Short-term neurological sequelae - children101271Risk Ratio (IV, Fixed, 95% CI)0.90 [0.72, 1.13]

    7.1 Low-income countries
3506Risk Ratio (IV, Fixed, 95% CI)1.08 [0.81, 1.43]

    7.2 High-income countries
7765Risk Ratio (IV, Fixed, 95% CI)0.67 [0.46, 0.97]

 8 Severe hearing loss in children due to non-Haemophilus influenzae species13862Risk Ratio (IV, Fixed, 95% CI)0.97 [0.66, 1.42]

    8.1 Low-income countries
2297Risk Ratio (IV, Fixed, 95% CI)1.20 [0.72, 2.00]

    8.2 High-income countries
11565Risk Ratio (IV, Fixed, 95% CI)0.73 [0.41, 1.31]

 9 Mortality - adults71517Risk Ratio (IV, Fixed, 95% CI)0.95 [0.82, 1.10]

    9.1 Low-income countries
3636Risk Ratio (IV, Fixed, 95% CI)1.02 [0.86, 1.20]

    9.2 High-income countries
4881Risk Ratio (IV, Fixed, 95% CI)0.76 [0.56, 1.04]

 10 Any hearing loss adults4844Risk Ratio (IV, Fixed, 95% CI)0.76 [0.57, 1.00]

    10.1 Low-income countries
1195Risk Ratio (IV, Fixed, 95% CI)0.86 [0.58, 1.28]

    10.2 High-income countries
3649Risk Ratio (IV, Fixed, 95% CI)0.67 [0.45, 0.99]

 
Comparison 6. Timing of steroids

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality223940Risk Ratio (IV, Random, 95% CI)0.87 [0.73, 1.05]

    1.1 Before or with first dose antibiotic
133143Risk Ratio (IV, Random, 95% CI)0.87 [0.69, 1.09]

    1.2 After first dose antibiotic
9797Risk Ratio (IV, Random, 95% CI)0.83 [0.55, 1.26]

 2 Severe hearing loss162300Risk Ratio (IV, Fixed, 95% CI)0.82 [0.64, 1.06]

    2.1 Before or with first dose antibiotic
101866Risk Ratio (IV, Fixed, 95% CI)0.81 [0.62, 1.07]

    2.2 After first dose antibiotic
6434Risk Ratio (IV, Fixed, 95% CI)0.89 [0.47, 1.68]

 3 Any hearing loss182754Risk Ratio (IV, Fixed, 95% CI)0.78 [0.68, 0.88]

    3.1 Before or with antibiotics
122257Risk Ratio (IV, Fixed, 95% CI)0.80 [0.70, 0.92]

    3.2 After first dose of antibiotics
6497Risk Ratio (IV, Fixed, 95% CI)0.62 [0.43, 0.89]

 4 Short-term neurologic sequelae121739Risk Ratio (IV, Fixed, 95% CI)0.85 [0.71, 1.03]

    4.1 Before or with first dose antibiotic
61282Risk Ratio (IV, Fixed, 95% CI)0.91 [0.73, 1.13]

    4.2 After first dose antibiotic
6457Risk Ratio (IV, Fixed, 95% CI)0.70 [0.47, 1.04]

 
Comparison 7. Study quality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality254121Risk Ratio (IV, Fixed, 95% CI)0.95 [0.85, 1.06]

    1.1 High quality
41793Risk Ratio (IV, Fixed, 95% CI)1.00 [0.88, 1.14]

    1.2 Medium quality
141477Risk Ratio (IV, Fixed, 95% CI)0.81 [0.57, 1.17]

    1.3 Low quality
7851Risk Ratio (IV, Fixed, 95% CI)0.79 [0.60, 1.04]

 2 Severe hearing loss172442Risk Ratio (IV, Fixed, 95% CI)0.72 [0.55, 0.95]

    2.1 High quality
3857Risk Ratio (IV, Fixed, 95% CI)0.99 [0.69, 1.41]

    2.2 Medium quality
101051Risk Ratio (IV, Fixed, 95% CI)0.47 [0.29, 0.75]

    2.3 Low quality
4534Risk Ratio (IV, Fixed, 95% CI)0.50 [0.20, 1.29]

 3 Any hearing loss202806Risk Ratio (IV, Fixed, 95% CI)0.79 [0.69, 0.90]

    3.1 High quality
41119Risk Ratio (IV, Fixed, 95% CI)0.90 [0.73, 1.12]

    3.2 Medium quality
121150Risk Ratio (IV, Fixed, 95% CI)0.73 [0.62, 0.87]

    3.3 Low quality
4537Risk Ratio (IV, Fixed, 95% CI)0.76 [0.38, 1.51]

 4 Short-term neurological sequelae131756Risk Ratio (IV, Fixed, 95% CI)0.85 [0.70, 1.03]

    4.1 High quality
3896Risk Ratio (IV, Fixed, 95% CI)0.97 [0.77, 1.23]

    4.2 Medium quality
8784Risk Ratio (IV, Fixed, 95% CI)0.63 [0.45, 0.89]

    4.3 Low quality
276Risk Ratio (IV, Fixed, 95% CI)0.83 [0.35, 1.95]

 
Comparison 8. Sensitivity analysis - worst-case scenario

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hearing loss172694Risk Ratio (M-H, Random, 95% CI)1.25 [0.81, 1.93]

 2 Any hearing loss203029Risk Ratio (M-H, Random, 95% CI)0.98 [0.71, 1.35]

 3 Short-term neurological sequelae131850Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.82, 1.18]

 4 Long-term neurological sequelae131758Risk Ratio (M-H, Random, 95% CI)1.18 [0.78, 1.78]