Do corticosteroids prevent hearing loss in pediatric bacterial meningitis? An analysis of the evidence.Abstract We reviewed the MEDLINE database of articles published from January 1966 through December 2001 in search of data on the ability of the corticosteroid dexamethasone dexamethasone /dex·a·meth·a·sone/ (dek?sah-meth´ah-son) a synthetic glucocorticoid used primarily as an antiinflammatory in various conditions, including collagen diseases and allergic states; it is the basis of a screening test in the diagnosis of Cushing's syndrome; used also as the acetate or sodium phosphate salt. to protect against sensorineural hearing loss in children with meningitis. We found 1,034 articles that matched our keyword entries, and after various exclusions, we winnowed this number down to 16 articles that contained adequate data regarding audiometric evaluation and follow-up. The 16 articles included reports of 11 randomized controlled trials (only 10 are considered in this analysis), two meta-analyses, two retrospective case series, and two consensus statements. Of the 10 clinical trials (all of which contained level I evidence), four showed that dexamethasone had a protective effect and six showed that it did not. The authors of the two meta-analyses (both level I) concluded that there was a protective effect, and the authors of the two retrospective case series (both level IV) concluded that there was not. Both consensus statements (both level V) recommended the use of dexamethasone only in Haemophilus influenzae meningitis. We conclude that well-designed studies with level I evidence have shown that the benefit of dexamethasone in preventing hearing loss in children with meningitis remains unclear. Significant variables in treatment response include the specific pathogen, the type of antibiotic, and the timing of dexamethasone administration. Introduction Bacterial meningitis affects approximately 15,000 infants and children in the United States each year. (1) Despite the availability of potent antimicrobial agents, 1.5 to 5% of children with bacterial meningitis die; among the survivors, 15 to 20% have significant long-term neurologic sequelae, such as epilepsy, motor dysfunction, and retardation. (2-4) These sequelae are more common in patients who have more severe disease at presentation, as is frequently seen in developing countries. (5-8) By far, the most common long-term effect of bacterial meningitis in children is sensorineural hearing loss (SNHL), which is often severe or profound and bilateral. (2,9,10) The reported incidence of SNHL ranges from 5% to more than 20%, depending on the type of audiologic surveillance. (11) During the past 2 decades, several excellent randomized trials have been conducted to investigate the effectiveness of the corticosteroid dexamethasone in preventing the sequelae of bacterial meningitis in infants and children. (12-21) However, results have been conflicting. (22,23) The aim of our review was to evaluate the quality of the evidence in these studies in the hope of arriving at a definitive conclusion about the ability of dexamethasone to protect against SNHL in children with bacterial meningitis. Materials and methods We searched the MEDLINE database of articles published from January 1966 through December 2001 using the MESH terms meningitis, hearing loss, and dexamethasone. The search identified 1,034 articles that matched the keyword entries. Of these, 170 articles were relevant to the protective effect of dexamethasone in bacterial meningitis. The abstracts of these articles were reviewed by 5 individuals: 3 senior otolaryngology faculty members, 1 pediatric otolaryngology fellow, and 1 senior resident. The reviewers categorized each report according to the 5-point grading system for data class developed by the Oxford Centre for Evidence-Based Medicine. After excluding reviews, case reports, non-English-language publications, editorial comments, etc., we were left with 65 articles that addressed the issue of dexamethasone and meningitis. Of these, 16 contained adequate data regarding audiometric evaluation and follow-up, and these articles served as the foundation of this evidence-based analysis. Results The 16 articles included 11 randomized controlled trials (only 10 of which are included in this analysis), (12-21) two meta-analyses, (22,23) two retrospective case series, (24,25) and two consensus statements (1,26) (tables 1 and 2). The evidence contained in all the clinical trials and both meta-analyses was rated as level I. The 2 case series were rated level IV, and the two consensus statements were rated level V. Of the level I reports, four randomized controlled trials (13,17,20,21) and both meta-analyses showed that dexamethasone did confer some beneficial effect in preventing SNHL, and six randomized controlled trials (12,14-16,18,19) showed that it did not (table 1). The authors of the two retrospective case series concluded that dexamethasone conferred no protective benefit. (24,25) Both consensus statements recommend the use of dexamethasone only in patients with Haemophilus influenzae meningitis. (1,26) We conclude, therefore, that the benefit of dexamethasone in preventing SNHL in children with meningitis remains unclear, despite the publication of well-designed studies with level I evidence. Significant variables affecting treatment response include the specific pathogen, the type of antibiotic, and the timing of dexamethasone administration. Discussion Two strategies have evolved to reduce the disease burden in patients with bacterial meningitis: (1) active immunization against the most common pathogens and (2) reduction of central nervous system inflammation with anti-inflammatory therapy. (18) Immunization is highly effective, and it has already significantly reduced the number of meningitis cases caused by H influenzae. (27-29) Steroids are the only anti-inflammatory agents that have been extensively studied in clinical trials for the prevention of neurologic complications of meningitis, including SNHL. There is good evidence that the inflammatory cascade induced by bacterial products during bacterial lysis is initiated and maintained by cytokines--tumor necrosis factor alpha (TNF-[alpha]) and interleukin- 1-beta (IL-1[beta]) in particular. (30-32) Studies in rabbits have shown that pretreatment with a steroid prior to intrathecal injection with H influenzae results in a reduction in concentrations of TNF-[alpha] and IL-1[beta]. (33-35) Similar findings have been seen in animal models of pneumococcal meningitis. (36,37) The modern era of steroid use in bacterial meningitis trials began in Dallas with a report of two double-blind, randomized trials by Lebel et al in 1988. (21) The first trial showed that patients who received adjunctive dexamethasone had a significantly lower rate of SNHL than did patients who received antibiotic alone. However, the antibiotic used in the first trial was cefuroxime cefuroxime /cef·u·rox·ime/ (sef?u-rok´sem) a semisynthetic, ß–resistant, second-generation cephalosporin effective against a wide range of gram-positive and gram-negative bacteria; used as the sodium salt and the axetil ester. cef·u·rox·ime (s, an agent that is not often used because it requires a relatively long time to sterilize the cerebrospinal fluid (CSF). (38,39) Additionally, most of the patients in that trial (77%) had H influenzae type b meningitis, which is believed to be more responsive to dexamethasone. Therefore, we did not include the results of that first study in this analysis. In the second arm of this study, which is included in this analysis, the authors used ceftriaxone ceftriaxone /cef·tri·ax·one/ (cef?tri-ak´son) a semisynthetic, ß–resistant, third-generation cephalosporin effective against a wide range of gram-positive and gram-negative bacteria, used as the sodium salt. cef·tri·ax·one (s, which is a much more effective agent and rapidly sterilizes CSE Dexamethasone was found to be protective in this study, as well. The reasons for the lack of definitive findings in these level I trials can be attributed to three variables: (1) the specific pathogen, (2) the type of antibiotic administered, and (3) the timing of dexamethasone administration. Pathogen. The three most common causative bacteria are H influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Dexamethasone was most protective in patients who had H influenzae meningitis. Those who had Spneumoniae or N meningitidis meningitis either did not respond to the steroid or their numbers were too small to allow for a meaningful conclusion. (1,24-26) Type of antibiotic. Ceftriaxone is more effective than both cefotaxime cefotaxime /cef·o·tax·ime/ (-tak´sem) a semisynthetic, broad-spectrum, ß–resistant, third-generation cephalosporin effective against a wide variety of gram-negative bacteria but less active against gram-positive cocci than are the first- and second-generation cephalosporins; used as the sodium salt. and cefuroxime in treating meningitis. (38,39) Studies in which cefotaxime and cefuroxime were used are potentially biased because these drugs enhance the protective effect of steroids. These two cephalosporins take a longer time to sterilize CSF in meningitis, and therefore the period of inflammation is extended. (40,41) There are no conclusive data on CSF sterilization with ampicillin ampicillin /am·pi·cil·lin/ (am?pi-sil´in) a semisynthetic, acid-resistant, penicillinase-sensitive penicillin used as an antibacterial against many gram-negative and gram-positive bacteria; also used as the sodium salt. am·pi·cil·lin ( plus chloramphenicol chloramphenicol /chlor·am·phen·i·col/ (klor?am-fen´i-kol) a broad-spectrum antibiotic effective against rickettsiae, gram-positive and gram-negative bacteria, and certain spirochetes; used also as the palmitate ester and as the sodium succinate derivative. or with other antibiotics that have been studied. Timing of the steroid dosage. In the four studies that showed that dexamethasone had a protective effect against SNHL, the steroid was administered either before the antibiotic, (13,21) concurrently with the antibiotic, (20) or within 4 hours of antibiotic administration. (17) A power analysis was not performed in any of the clinical trials. The only such analysis was conducted by Geiman and Smith in their meta-analysis. (23) Their power analysis showed that bilateral SNHL occurred with greater frequency in patients who did not receive a steroid. This was significant in view of the number of patients who were included in the analysis. However, one of the studies in this meta-analysis included adults. In the meta-analysis by McIntyre et al, the authors reached a similar conclusion without a power analysis. (22) However, the beneficial effect of dexamethasone was seen only in patients who had H influenzae b infection. Also, in patients with S pneumoniae meningitis, the meta-analysis found that dexamethasone had a protective effect only when it was administered prior to antibiotic administration. No statistically significant incidence of steroid-related side effects in the treatment of meningitis has been reported. (23,25) The duration of steroid treatment does not influence its protective effect, as shown by Syrogiannopoulos et al in a comparison of 2- and 4-day regimens. (42) Audiometric follow-up in the 16 studies varied widely, and the stability of SNHL was not examined. However, experience gained during two other studies indicates that SNHL after meningitis can be progressive in patients with H influenzae and Spneumoniae infections. (43,44) An additional consideration is ossification of the labyrinth in children with SNHL after meningitis; in a retrospective study (level IV) reported by Hartnick et al in 2001, dexamethasone was shown to have a protective effect against cochlear ossification after meningitis. (45) In conclusion, the current literature suggests that there is grade B evidence in favor of the use of dexamethasone in patients with H influenzae-associated meningitis and grade C evidence for its use in patients with other bacteria. (A grade of B indicates consistent results in level II or III studies or extrapolations from level I studies; a grade of C indicates data from level IV studies or extrapolations from level II or III studies.) References (1.) American Academy of Pediatrics Committee on Infectious Diseases: Dexamethasone therapy for bacterial meningitis in infants and children. Pediatrics 1990;86:130-3. (2.) Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD. Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 1990;323:1651-7. (3.) Oostenbrink R, Maas M, Moons KG, Moll HA. Sequelae after bacterial meningitis in childhood. Scand J Infect Dis 2002;34: 379-82. (4.) del Rio MA, Chrane D, Shelton S, et al. Ceftriaxone versus ampicillin and chlorampbenicol for treatment of bacterial meningitis in children. Lancet 1983;1:1241-4. (5.) Salih MA, Khaleefa OH, Bushara M, et al. Long term sequelae of childhood acute bacterial meningitis in a developing country. A study from the Sudan. Scand J Infect Dis 1991;23:175-82. (6.) Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: A randomised controlled trial. Lancet 2002;360:211-8. (7.) McCracken GH Jr. Rich nations, poor nations, and bacterial meningitis. Lancet 2002;360:183. (8.) Kilpi T, Anttila M, Kallio MJ, Peltola H. Length of prediagnostic history related to the course and sequelae of childhood bacterial meningitis. Pediatr Infect Dis J 1993;12:184-8. (9.) Rasmussen N, Johnsen NJ, Bohr VA. Otologic sequelae after pneumococcal meningitis: A survey of 164 consecutive cases with a follow-up of 94 survivors. Laryngoscope 1991;101:876-82. (10.) Yurkowski PJ, Plaisance KI. Prevention of auditory sequelae in pediatric bacterial meningitis: A meta-analysis. Pharmacotherapy 1993;13:494-9. (11.) 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;311:869-74. (12.) Daoud AS, Batieha A, Al-Sheyyab M, et al. Lack of effectiveness of dexamethasone in neonatal bacterial meningitis. Eur J Pediatr 1999;158:230-3. (13.) Kulahli I, Ozturk M, Bilen C, et al. Evaluation of hearing loss with auditory brainstem responses in the early and late period of bacterial meningitis in children. J Laryngol Otol 1997;111:223-7. (14.) Qazi SA, Khan MA, Mughal N, et al. Dexamethasone and bacterial meningitis in Pakistan. Arch Dis Child 1996;75:482-8. (15.) Kilpi T, Peltola H, Jauhiainen T, Kallio MJ. Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group. Pediatr Infect Dis J 1995;14:270-8. (16.) Kanra GY, Ozen H, Secmeer G, et al. Beneficial effects of dexamethasone in children with pneumococcal meningitis. Pediatr Infect Dis J 1995:14:490-4. (17.) Wald ER, Kaplan SL, Mason EO Jr., et al. Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group. Pediatrics 1995;95:21-8. (18.) Schaad UB, Lips U, Gnehm HE, et al. Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group. Lancet 1993;342:457-61. (19.) Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991;324:1525-31. (20.) Girgis NI, Farid Z, Mikhail IA, et al. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 1989:8:848-51. (21.) Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. N Engl J Med 1988;319:964-71. (22.) McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA 1997;278:925-31. (23.) Geiman BJ, Smith AL. Dexamethasone and bacterial meningitis. A meta-analysis of randomized controlled trials. West J Med 1992;157:27-31. (24.) Arditi M, Mason EO Jr., Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: Clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998;102:1087-97. (25.) Kennedy WA, Hoyt MJ, McCracken GH Jr. The role of corticosteroid therapy in children with pneumococcal meningitis. Am J Dis Child 1991;145:1374-8. (26.) The Meningitis Working Party of the British Paediatric Immunology and Infectious Diseases Group. Should we use dexamethasone in meningitis? Arch Dis Child 1992;67:1398-1401. (27.) Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: Global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 2000;13: 302-17. (28.) Wenger JD. Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus influenzae type b conjugate vaccines in the United States and Canada. Pediatr Infect Dis J 1998;17 (9 suppl):S 132-6. (29.) Stein LK, Boyer KM. Progress in the prevention of hearing loss in infants. Ear Hear 1994:15:116-25. (30.) Tracey KJ, Vlassara H, Cerami A. Cachectin cachectin /ca·chec·tin/ (-tin) former name for tumor necrosis factora. ca·chec·tin (k -k k/tumour necrosis
factor. Lancet 1989;1:1122-6.(31.) Dinarello CA, Cannon JG, Wolff SM. New concepts on the pathogenesis of fever. Rev Infect Dis 1988;10:168-89. (32.) Dinarello CA. Interleukin-1. Rev Infect Dis 1984;6:51-95. (33.) Mustafa MM, Ramilo O, Mertsola J, et al. Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis. J Infect Dis 1989;160: 818-25. (34.) Mustafa MM, Ramilo O, Saez-Llorens X, et al. Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients. Am J Dis Child 1990;144:883-7. (35.) Bakhiet M, Mustafa M, Zhu J, et al. Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis. Clin Exp Immunol 1998;114: 398-402. (36.) Tauber MG, Khayam-Bashi H, Sande MA. Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis. J Infect Dis 1985;151:528-34. (37.) Ramilo O, Saez-Llorens X, Mertsola J, et al. Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med 1990;172:497-507. (38.) Lebel MH, McCracken GH Jr. Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. Pediatrics 1989;83:161-7. (39.) Schaad UB, Suter S, Gianella-Borradori A, et al. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 1990;322:141-7. (40.) Kaplan SL. Adjuvant therapy in meningitis. Adv Pediatr Infect Dis 1995;10:167-86. (41.) Kaplan SL. Dexamethasone for children with bacterial meningitis. Should it be routine therapy? Am J Dis Child 1989;143:290-2. (42.) Syrogiannopoulos GA, Lourida AN, Theodoridou MC, et al. Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen. J Infect Dis 1994;169:853-8. (43.) Bhatt SM, Lauretano A, Cabellos C, et al. Progression of hearing loss in experimental pneumococcal meningitis: Correlation with cerebrospinal fluid cytochemistry cytochemistry /cy·to·chem·is·try/ (-kem´is-tre) the identification and localization of the different chemical compounds and their activities within the cell. cy·to·chem·is·try (s . J Infect Dis 1993;167:675-83.(44.) Silkes ED, Chabot J. Progressive hearing loss following Haemophilus influenzae meningitis. Int J Pediatr Otorhinolaryngol 1985:9:249-56. (45.) Hartnick CJ, Kim HH, Chute PM, Parisier SC. Preventing labyrinthitis ossificans: The role of steroids. Arch Otolaryngol Head Neck Surg 2001;127:180-3. From the Department of Otolaryngology--Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York City. Reprint requests: Spiros Manolidis, MD, Department of Otolaryngology--Head and Neck Surgery, Columbia University, HP813, 180 Fort Washington, New York, NY 10032. Phone: (212) 305-5335; fax: (212) 305-3975; e-mail: smanolidis@mac.com Spiros Manolidis MD; Romaine Johnson, MD
Table 1. Summary of the 16 articles
Evidence
Authors Description level
Daoud (RCT) examined the effects of dexamethasone I
et al, (12) on neurologic sequelae in
1999 neonates with bacterial meningitis.
N = 52
Kulahli RCT compared adjunctive dexamethasone I
et al, (13) with placebo in reducing the risk of
SNHL in bacterial meningitis in children.
Dexamethasone was given 20 minutes
prior to parenteral antibiotics at a dose of
0.6 mg/kg/day for 4 doses.
N=50
Qazi et RCT compared dexamethasone's effects I
al, (14) on hearing loss and neurologic and
1996 developmental outcomes in children with
bacterial meningitis. Dexamethasone was
given prior to parenteral antibiotics at 0.6
mg/kg/day in four doses.
N = 89
Kilpi et RCT measured the effects of I
al, (15) dexamethasone and glycerol in the
1995 treatment of bacterial meningitis in infants
and children.
N = 122
Kanra et RCT compared dexamethasone with I
al, (16) placebo in children older than 2 years
1995 who had pneumococcal meningitis.
Dexamethasone was given 20 minutes
prior to parenteral antibiotics at 0.6 mg/
kg/day in four doses.
N=60
Wald et Multicenter RCT was conducted to I
al, (17) assess the efficacy of dexamethasone
1995 as an adjunctive therapy for bacterial
meningitis in children. Dexamethasone
was given at a dose of 0.15 mg/kg/day
for 4 days within 4 hours of the antibiotic
dose.
N = 173
Schaad et RCT examined the use of dexamethasone I
al, (18) in children with bacterial meningitis.
1993 Dexamethasone was given 10 minutes
prior to a parenteral antibiotic at a dose
of 0.4 mg/kg/day for 2 days.
N=115
Odio et RCT assessed the effects of adjuvant I
al, (19) dexamethasone in bacterial meningitis in
1991 children. The steroid was given 15 to 20
minutes prior to a parenteral antibiotic
for 4 days at a dose of 0.6 mg/kg/day.
N= 101
Girgis et RCT assessed ampicillin and I
al, (20) chloramphenicol with and without
1989 dexamethasone given on a nonselective
alternating basis to children and adults
(8 mg for patients younger than 12 years
and 12 mg for those older) for 3 days. The
steroid was given concomitantly with the
antibiotics.
N = 429
Lebel et Two RCTs compared the efficacy of an I
al (21) antibiotic with and without adjunctive
1988 dexamethasone in the treatment
of bacterial meningitis in children.
Dexamethasone was given at a dose of
0.15 mg/kg/day for 4 days.
N = 200
McIntyre et Meta-analysis included 11 RCTs published I
al, (22) from January 1988 through November
1997 1996 on the use of dexamethasone as an
adjunctive therapy for bacterial meningitis.
Geiman and Meta-analysis evaluated 5 RCTs in children I
Smith, and 1 study with children and adults to
(23) 1992 evaluate the effect of dexamethasone as
an adjunctive therapy for the treatment
of bacterial meningitis. Studies were
published between 1989 and 1991.
Arditi et Retrospective case series looked at IV
al, (24) children with pneumococcal meningitis.
1998 Some 40 children (22%) were treated with
dexamethasone.
N = 180
Kennedy et Retrospective case series reviewed IV
al, (25) patients admitted and treated for
1991 pneumococcal meningitis and given
steroids. Some patients were part of
clinical trials of dexamethasone therapy.
N=97
British Consensus statement addressed the V
Paediatric efficacy and safety of dexamethasone in
Immunology children with bacterial meningitis.
and
Infectious
Diseases
Group,
(26) 1992
American Consensus statement addressed V
Academy of dexamethasone therapy for bacterial
Pediatrics, meningitis in infants and children,
(1) 1990
Authors Summary
Daoud The dexamethasone group had 2 infants
et al, (12) with SNHL, compared with 1 in the control
1999 group (7.4 vs. 4%). The difference was not
statistically significant. No power analysis
was performed.
Kulahli Fewer patients in the dexamethasone
et al, (13) group developed mild and severe persistent
hearing loss (19 vs. 38%). No power
analysis was performed. No p values for
cumulative hearing loss data were reported.
Qazi et Authors found no statistically significant
al, (14) difference in outcomes between the
1996 dexamethasone group and the placebo
controls with respect to hearing loss at 1
and 12 months postinfection. Authors used
multivariate analysis to control for factors
other than dexamethasone use, including
duration of illness prior to admission.
Kilpi et Some 10% of study participants
al, (15) developed SNHL. Hearing loss was more
1995 common in patients who were not given
dexamethasone, although the difference
did not reach statisical significance
(p=0.14). No power analysis was performed.
Kanra et The incidence of both unilateral and
al, (16) bilateral SNHL was lower in the
1995 dexamethasone-treated group, but the
difference was not statistically significant
(7.4 vs. 23%; p = 0.11). No power analysis
was performed.
Wald et Overall, no difference in audiometric
al, (17) outcomes between the dexamethasone
1995 group and the placebo controls was
observed. However, patients with
Hib-induced meningitis who were treated with
dexamethasone had a significantly lower
rate of SIN HL (p=0.02).
Schaad et Authors found a higher incidence of SNHL
al, (18) in the placebo group, but the difference
1993 did not reach statistical significance (5 vs.
15%; p = 0.11). No power analysis was
performed.
Odio et SNHL was more common in the placebo
al, (19) controls, but the difference did not reach
1991 statistical significance (6 vs. 16%; p=
0.18). No power analysis was performed.
Girgis et The incidence of SNHL was lower among
al, (20) those who received dexamethasone, but
1989 the advantage was statistically significant
only in patients who had Streptococcus
pneumoniae infections (p = 0.05).
Lebel et Children who received dexamethasone
al (21) were significantly less likely to experience
1988 SNHL than were placebo controls (3 vs.
15.5%; p < 0.01). *
* Second arm of this study.
McIntyre et Dexamethasone provided protection
al, (22) against SNHL in patients with Hib
1997 meningitis and pneumococcal infection
when given prior to parenteral antibiotics.
Geiman and Placebo controls had a higher relative
Smith, risk of bilateral SNHL and the need for
(23) 1992 hearing aids (relative risks: 4.12 and 20.94,
respectively). The difference between
groups in unilateral hearing loss was not
statistically significant (relative
risk: 1.09).
Arditi et The incidence of SNHL was higher in
al, (24) dexamethasone patients than in placebo
1998 controls (46 vs. 23%). However, the
authors noted a trend toward giving the
steroid to sicker children; when this trend
was taken into account, the difference
in SNHL was no longer statistically
significant.
Kennedy et Moderate or worse bilateral hearing loss
al, (25) was less common in the steroid-treated
1991 patients, but not significantly so
(p = 0.13).
British Children with Hib meningitis probably
Paediatric benefit from dexamethasone in terms of
Immunology SNHL, but there is no current evidence
and that children with pneumococcal meningitis
Infectious have better outcomes when they are
Diseases treated with steroids.
Group,
(26) 1992
American Dexamethasone probably prevents SNHL
Academy of in patients with Hib meningitis, and it
Pediatrics, should be considered on an individual
(1) 1990 basis. The steroid should be administered
at the time of the first dose of antibiotic.
Its utility for treatment of pneumococcal or
meningococcal meningitis is not known.
Key: RCT = randomized controlled trial; SNHL = sensorineural
hearing loss; Hib = Haemophilus influenzae type b
Table 2. Additional data on the 10 randomized
controlled trials and 2 case series
Timing of
Authors Bacteria (% of cases) steroid dose
Daoud et al, (12) Klebsiella pneumoniae, 44% Before
1999 Enterobacter spp., 17% antibiotic
Staphylococcus aureus, 4%
Kulahli et al, (13) Streptococcus pneumoniae, 20% Before
1997 Neisseria meningitidis, 20% antibiotic
Haemophilus influenzae, 12%
Qazi et al, (14) H influenzae type b, 45% Before
1996 N meningitidis, 17% antibiotic
S pneumoniae, 13%
Kilpi et al, (15) H influenzae type b, 53% Concomitantly
1995 N meningitides, 33%
S pneumoniae, 10%
Kanra et al, (16) S pneumoniae, 100% Before
1995 antibiotic
Wald et al, (17) H influenzae type b, 58% Within
1995 S pneumoniae, 23% 4 hours of
N meningitides, 17% antibiotic
Schaad et al, (18) H influenzae type b, 58% Before
1993 N meningitidis, 24% antibiotic
S pneumoniae, 9%
Odio et al, (19) H influenzae type b, 78% Before
1991 N meningitidis, 8% antibiotic
S pneumoniae, 2%
Girgis et al, (20) N meningitidis, 60% Concomitantly
1989 S pneumoniae, 25%
H influenzae type b, 13%
Lebel et al, (21) H influenzae type b, 77% Before
1988 N meningitides, 8% antibiotic
S pneumoniae, 8%
Arditi et al, (24) S pneumoniae, 100% Before
1998 antibiotic
Kennedy et al, (25) S pneumoniae, 100% Not
1991 reported
Audiometric
Authors Antibiotic follow-up
Daoud et al, (12) Cefotaxime plus Year 2
1999 ampicillin
Kulahli et al, (13) Penicillin G Days 2 and 10,
1997 Chloramphenicol week 8
Qazi et al, (14) Ampicillin Months 1, 4,
1996 Chloramphenicol and 12
Kilpi et al, (15) Ceftriaxone 2 months
1995 postdischarge
Kanra et al, (16) Ampicillin/ Week 6, month
1995 sulbactam 3, year 1
Wald et al, (17) Ceftriaxone Admission,
1995 week 6, month
12
Schaad et al, (18) Ceftriaxone Days 2 and
1993 4, discharge,
months 3 and 9
Odio et al, (19) Cefotaxime Discharge,
1991 months 4 and
24
Girgis et al, (20) Ampicillin When awake,
1989 Chloramphenicol months 1
through 6
Lebel et al, (21) Ceftriaxone * Within 6 weeks
1988 * Second
arm of this
study
Arditi et al, (24) Cefotaxime Not reported
1998 Ceftriaxone
Penicillin
Vancomycin
Meropenem
Clindamycin
Kennedy et al, (25) Cefotaxime End of therapy,
1991 Ceftriaxone months 2
Cefuroxime through 6
Ampicillin
Penicillin
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