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September 1989, Vol 143, No. 9 >
Article | September 1989

Corticosteroids as Adjunctive Therapy in Bacterial Meningitis:  A Meta-analysis of Clinical Trials FREE

Peter L. Havens, MD, MS; Karen J. Wendelberger, MD; George M. Hoffman, MD; Martha B. Lee, PhD; Michael J. Chusid, MD
[+] Author Affiliations

Accepted for publication February 13, 1989.

Reprint requests to Children's Hospital of Wisconsin, PO Box 1997, Milwaukee. WI 53201 (Dr Havens).


Am J Dis Child. 1989;143(9):1051-1055. doi:10.1001/archpedi.1989.02150210085023.
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References
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• A meta-analysis of all nine available controlled trials of corticosteroids for adjunctive therapy for bacterial meningitis was performed. Risks of various outcomes were assessed for control and treatment groups from each study, and risk differences were determined. For each outcome a weighted average of the individual risk differences was calculated. The results show that corticosteroid administration did not reduce the risk of death or neurologic abnormality at hospital discharge or follow-up examination. Based on statistically combined results of the three most recent trials, there is evidence that dexamethasone reduces the risk of bilateral moderate or more severe hearing loss (risk difference, − 9%; 95% confidence limits, −15% and −3%). However, this may be true only for children with meningitis caused by Haemophilus influenzae type b. There are inadequate data in adults or in children with meningitis due to other organisms to demonstrate the benefit of dexamethasone administration. Further study is necessary to fully assess the benefits and risks of corticosteroids for adjunctive therapy for bacterial meningitis.

(AJDC. 1989;143:1051-1055)

REFERENCES

1 +
Klein JO, Feigin RD, McCracken GH.  Report of the task force on diagnosis and management of meningitis . Pediatrics . 1986;;78:955-982.
2 +
Marks WA, Stutman HR. Marks MI, et al.  Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial . J Pediatr . 1986;:109:123-130
3 +
Congeni BL.  Comparison of ceftriaxone and traditional therapy of bacterial meningitis . Antimicrob Agents Chemother . 1984;;25:40-44.
4 +
DelRio MA, Chrane D, Shelton S, McCracken GH, Nelson JD.  Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children . Lancet . 1983;;1:1241-1244.
5 +
Swedish Study Group.  Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis . Lancet . 1982;;1:295-298.
6 +
Feigin RD, Stechenberg BW, Chang MJ, et al.  Prospective evaluation of treatment of Hemophilus influenzae meningitis . J Pediatr . 1976;;88: 542-548.
7 +
Herson VC, Todd JK.  Prediction of morbidity in Hemophilus influenzae meningitis . Pediatrics . 1977;;59:35-39.
8 +
Lindberg J, Rosenhall U, Nylen O, Ringner A.  Long-term outcome of Hemophilus influenzae meningitis related to antibiotic treatment . Pediatrics . 1977;;60:1-6.
9 +
Feldman WE, Ginsburg CM, McCracken GH, et al.  Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis . J Pediatr . 1982;;100:209-212.
10 +
Sell S.  Long term sequelae of bacterial meningitis in children . Pediatr Infect Dis . 1983;;2:90-93.
11 +
Claesson B, Trollfors B, Jodal U, Rosenhall U.  Incidence and prognosis of Haemophilus influenzae meningitis in children in a Swedish region . Pediatr Infect Dis . 1984;;3:35-39.
12 +
Smith AL.  Neurologic sequelae of meningitis . N Engl J Med . 1988;;319:1012-1014.
13 +
Kaplan SL, Catlin FI, Weaver T, Feigin RD.  Onset of hearing loss in children with bacterial meningitis . Pediatrics . 1984;;73:575-578.
14 +
Vienny H, Despland PA, Lutschg J, Deonna T, Dutoit-Marco ML, Gander C.  Early diagnosis and evolution of deafness in childhood bacterial meningitis: a study using brainstem auditory evoked potentials . Pediatrics . 1984;;73:579-586.
15 +
Dodge PR, Davis H, Feigin RD, et al.  Prospective evaluation of hearing impairment as a sequela of acute bacterial meningitis . N Engl J Med . 1984;;311:869-874.
16 +
Ozdamar O, Kraus N, Stein L.  Auditory brainstem responses in infants recovering from bacterial meningitis . Arch Otolaryngol Head Neck Surg . 1983;;109:13-18.
17 +
Cassidy JE.  Therapy in collapse due to meningococcus infection . Ann Intern Med . 1957;; 46:1099-1104.
18 +
Lepper MH, Spies HW.  The use of intravenous hydrocortisone as supplemental treatment in acute bacterial meningitis . Antibiot Annu . 1957;-1958:336-349.
19 +
Ribble JC, Braude AI.  ACTH and adrenal steroids in the treatment of pneumococcal meningitis in adults . Am J Med . 1958;;24:68-79.
20 +
Lepper MH, Spies HW.  Treatment ofpneumococcic meningitis . Arch Intern Med . 1959;;104: 252-259.
21 +
Cooperative Study Group.  The effectiveness of hydrocortisone in the management of severe infections . JAMA . 1963;;183:462-465.
22 +
Reynolds RC.  Pneumococcal meningitis: the effect of adrenal steroids on the level of consciousness . Bull Johns Hopkins Hosp . 1966;;119:276-282.
23 +
Weiss W, Figueroa W, Shapiro WH, Flippin HF.  Prognostic factors in pneumococcal meningitis . Arch Intern Med . 1967;;120:517-524.
24 +
DeLemos RA, Haggerty RJ.  Corticosteroids as an adjunct to treatment in bacterial meningitis: a controlled clinic trial . Pediatrics . 1969;; 44:30-34.
25 +
Belsey MA, Hoffpauir CW, Smith MH.  Dexamethasone in the treatment of acute bacterial meningitis: the effect of study design on the interpretation of results . Pediatrics . 1969;;44:503-513.
26 +
Jensen K, Ranek L, Rosdahl N.  Bacterial meningitis: a review of 356 cases with special reference to corticosteroid and antiserum treatment . Scand J Infect Dis . 1969;;1:21-30.
27 +
Abello VB, Riley HD.  The use of adrenal corticosteroids in the management of meningitis . Okla State Med Assoc J . 1972;;65:255-261.
28 +
Bademosi O, Osuntokun BO.  Prednisolone in the treatment of pneumococcal meningitis . Trop Geogr Med . 1979;;31:53-56.
29 +
Lebel MH, Freji BJ, Syrogiannopoulos GA, et al.  Dexamethasone therapy for bacterial meningitis: results of two double-blind, placebo-controlled trials . N Engl J Med . 1988;;319:964-971.
30 +
Lebel MH, Hoyt MJ, Waagner DC, Rollins NK, Finitzo T, McCracken GH Jr.  Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis . AJDC . 1989;;143:301-306.
31 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials . Controlled Clin Trials . 1986;;77:177-188.
32 +
Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC.  Meta-analyses of randomized controlled trials . N Engl J Med . 1987;;316:450-455.
33 +
Bulpitt CJ.  Meta-analysis . Lancet . 1988;;2: 93-94.
34 +
Harbin GL, Hodges GR.  Corticosteroids as adjunctive therapy for acute bacterial meningitis . South Med J. 1979;;72:977-980.
35 +
Tuomanen E.  Partner drugs: a new outlook for bacterial meningitis . Ann Intern Med . 1988;; 109:690-692.
36 +
 Steroids in bacterial meningitis: helpful or harmful? Lancet . 1982;;1:1164. Editorial.
37 +
Weitman S, Berger S.  Clinical trial design in studies of corticosteroids for bacterial infections . Ann Intern Med . 1974;;81:36-42.
38 +
Krober M.  Use of corticosteroids in the treatment of infectious diseases . South Med J . 1974;;67:728-732.
39 +
Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons Inc; 1981;.
40 +
Feigin RD.  Bacterial meningitis beyond the neonatal period.  In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases . Philadelphia, Pa: WB Saunders Co; 1987;:439-465.
41 +
Jones FE, Hanson DR. H. influenzae meningitis treated with ampicillin or choloramphenicol, and subsequent hearing loss. Dev Med Child Neurol . 1977;;19:593-597.
42 +
Richner B, Hof E, Prader A.  Hearing impairment following therapy of Haemophilus influenzae meningitis . Helv Paediatr Acta . 1979;; 34:443-447.
43 +
Kaplan SL.  Dexamethasone for children with bacterial meningitis: should it be routine therapy? AJDC . 1989;;143:290-292.
44 +
Leeder JS, Gold R.  Cephalosporins . In: Koren G, Prober CG, Gold R, eds. Antimicrobial Therapy in Infants and Children . New York, NY: Marcel Dekker Inc; 1988;:173-235.
45 +
Schaad UB, Nelson JD, McCracken GH.  Recrudescence and relapse in bacterial meningitis of childhood . Pediatrics . 1981;;67:188-195.
46 +
Brady MT, Kaplan SL, Taber LH.  Association between persistence of pneumococcal meningitis and dexamethasone administration . J Pediatr . 1981;;99:924-926.

Figures

Tables

Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Klein JO, Feigin RD, McCracken GH.  Report of the task force on diagnosis and management of meningitis . Pediatrics . 1986;;78:955-982.
2 +
Marks WA, Stutman HR. Marks MI, et al.  Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial . J Pediatr . 1986;:109:123-130
3 +
Congeni BL.  Comparison of ceftriaxone and traditional therapy of bacterial meningitis . Antimicrob Agents Chemother . 1984;;25:40-44.
4 +
DelRio MA, Chrane D, Shelton S, McCracken GH, Nelson JD.  Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children . Lancet . 1983;;1:1241-1244.
5 +
Swedish Study Group.  Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis . Lancet . 1982;;1:295-298.
6 +
Feigin RD, Stechenberg BW, Chang MJ, et al.  Prospective evaluation of treatment of Hemophilus influenzae meningitis . J Pediatr . 1976;;88: 542-548.
7 +
Herson VC, Todd JK.  Prediction of morbidity in Hemophilus influenzae meningitis . Pediatrics . 1977;;59:35-39.
8 +
Lindberg J, Rosenhall U, Nylen O, Ringner A.  Long-term outcome of Hemophilus influenzae meningitis related to antibiotic treatment . Pediatrics . 1977;;60:1-6.
9 +
Feldman WE, Ginsburg CM, McCracken GH, et al.  Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis . J Pediatr . 1982;;100:209-212.
10 +
Sell S.  Long term sequelae of bacterial meningitis in children . Pediatr Infect Dis . 1983;;2:90-93.
11 +
Claesson B, Trollfors B, Jodal U, Rosenhall U.  Incidence and prognosis of Haemophilus influenzae meningitis in children in a Swedish region . Pediatr Infect Dis . 1984;;3:35-39.
12 +
Smith AL.  Neurologic sequelae of meningitis . N Engl J Med . 1988;;319:1012-1014.
13 +
Kaplan SL, Catlin FI, Weaver T, Feigin RD.  Onset of hearing loss in children with bacterial meningitis . Pediatrics . 1984;;73:575-578.
14 +
Vienny H, Despland PA, Lutschg J, Deonna T, Dutoit-Marco ML, Gander C.  Early diagnosis and evolution of deafness in childhood bacterial meningitis: a study using brainstem auditory evoked potentials . Pediatrics . 1984;;73:579-586.
15 +
Dodge PR, Davis H, Feigin RD, et al.  Prospective evaluation of hearing impairment as a sequela of acute bacterial meningitis . N Engl J Med . 1984;;311:869-874.
16 +
Ozdamar O, Kraus N, Stein L.  Auditory brainstem responses in infants recovering from bacterial meningitis . Arch Otolaryngol Head Neck Surg . 1983;;109:13-18.
17 +
Cassidy JE.  Therapy in collapse due to meningococcus infection . Ann Intern Med . 1957;; 46:1099-1104.
18 +
Lepper MH, Spies HW.  The use of intravenous hydrocortisone as supplemental treatment in acute bacterial meningitis . Antibiot Annu . 1957;-1958:336-349.
19 +
Ribble JC, Braude AI.  ACTH and adrenal steroids in the treatment of pneumococcal meningitis in adults . Am J Med . 1958;;24:68-79.
20 +
Lepper MH, Spies HW.  Treatment ofpneumococcic meningitis . Arch Intern Med . 1959;;104: 252-259.
21 +
Cooperative Study Group.  The effectiveness of hydrocortisone in the management of severe infections . JAMA . 1963;;183:462-465.
22 +
Reynolds RC.  Pneumococcal meningitis: the effect of adrenal steroids on the level of consciousness . Bull Johns Hopkins Hosp . 1966;;119:276-282.
23 +
Weiss W, Figueroa W, Shapiro WH, Flippin HF.  Prognostic factors in pneumococcal meningitis . Arch Intern Med . 1967;;120:517-524.
24 +
DeLemos RA, Haggerty RJ.  Corticosteroids as an adjunct to treatment in bacterial meningitis: a controlled clinic trial . Pediatrics . 1969;; 44:30-34.
25 +
Belsey MA, Hoffpauir CW, Smith MH.  Dexamethasone in the treatment of acute bacterial meningitis: the effect of study design on the interpretation of results . Pediatrics . 1969;;44:503-513.
26 +
Jensen K, Ranek L, Rosdahl N.  Bacterial meningitis: a review of 356 cases with special reference to corticosteroid and antiserum treatment . Scand J Infect Dis . 1969;;1:21-30.
27 +
Abello VB, Riley HD.  The use of adrenal corticosteroids in the management of meningitis . Okla State Med Assoc J . 1972;;65:255-261.
28 +
Bademosi O, Osuntokun BO.  Prednisolone in the treatment of pneumococcal meningitis . Trop Geogr Med . 1979;;31:53-56.
29 +
Lebel MH, Freji BJ, Syrogiannopoulos GA, et al.  Dexamethasone therapy for bacterial meningitis: results of two double-blind, placebo-controlled trials . N Engl J Med . 1988;;319:964-971.
30 +
Lebel MH, Hoyt MJ, Waagner DC, Rollins NK, Finitzo T, McCracken GH Jr.  Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis . AJDC . 1989;;143:301-306.
31 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials . Controlled Clin Trials . 1986;;77:177-188.
32 +
Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC.  Meta-analyses of randomized controlled trials . N Engl J Med . 1987;;316:450-455.
33 +
Bulpitt CJ.  Meta-analysis . Lancet . 1988;;2: 93-94.
34 +
Harbin GL, Hodges GR.  Corticosteroids as adjunctive therapy for acute bacterial meningitis . South Med J. 1979;;72:977-980.
35 +
Tuomanen E.  Partner drugs: a new outlook for bacterial meningitis . Ann Intern Med . 1988;; 109:690-692.
36 +
 Steroids in bacterial meningitis: helpful or harmful? Lancet . 1982;;1:1164. Editorial.
37 +
Weitman S, Berger S.  Clinical trial design in studies of corticosteroids for bacterial infections . Ann Intern Med . 1974;;81:36-42.
38 +
Krober M.  Use of corticosteroids in the treatment of infectious diseases . South Med J . 1974;;67:728-732.
39 +
Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons Inc; 1981;.
40 +
Feigin RD.  Bacterial meningitis beyond the neonatal period.  In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases . Philadelphia, Pa: WB Saunders Co; 1987;:439-465.
41 +
Jones FE, Hanson DR. H. influenzae meningitis treated with ampicillin or choloramphenicol, and subsequent hearing loss. Dev Med Child Neurol . 1977;;19:593-597.
42 +
Richner B, Hof E, Prader A.  Hearing impairment following therapy of Haemophilus influenzae meningitis . Helv Paediatr Acta . 1979;; 34:443-447.
43 +
Kaplan SL.  Dexamethasone for children with bacterial meningitis: should it be routine therapy? AJDC . 1989;;143:290-292.
44 +
Leeder JS, Gold R.  Cephalosporins . In: Koren G, Prober CG, Gold R, eds. Antimicrobial Therapy in Infants and Children . New York, NY: Marcel Dekker Inc; 1988;:173-235.
45 +
Schaad UB, Nelson JD, McCracken GH.  Recrudescence and relapse in bacterial meningitis of childhood . Pediatrics . 1981;;67:188-195.
46 +
Brady MT, Kaplan SL, Taber LH.  Association between persistence of pneumococcal meningitis and dexamethasone administration . J Pediatr . 1981;;99:924-926.

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