ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 1 مورد

Bacterial meningitis in children: Role of dexamethasone

Bacterial meningitis in children: Role of dexamethasone
Author:
Sheldon L Kaplan, MD
Section Editors:
Morven S Edwards, MD
Douglas R Nordli, Jr, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Apr 2025. | This topic last updated: Mar 21, 2025.

INTRODUCTION — 

Bacterial meningitis can cause substantial morbidity and mortality. The risk of dying or of developing complications depends upon the causative pathogen, age of the patient, comorbidities, severity of illness, and timeliness of antibiotic therapy. (See "Bacterial meningitis in children older than one month: Treatment and prognosis".)

Potential acute and long-term neurologic complications of bacterial meningitis include (see "Bacterial meningitis in children: Neurologic complications"):

●Acute complications:

•Seizures

•Subdural effusion and empyema

•Cerebrovascular complications (eg, arterial stoke, cerebral venous thrombosis)

•Cerebral edema

•Ventricular enlargement or hydrocephalus

•Brain abscess

●Long-term complications:

•Hearing loss

•Vision impairment

•Seizures

•Hydrocephalus

•Behavior and emotional disorders (eg, attention deficit hyperactivity disorder, mood disorders, social difficulties)

•Cognitive impairment

•Motor disability (including cerebral palsy)

The use of dexamethasone to prevent neurologic complications of bacterial meningitis in children will be discussed here. Other aspects of treatment of bacterial meningitis in infants and children and details regarding neurologic complications of bacterial meningitis are discussed separately:

●(See "Bacterial meningitis in children older than one month: Treatment and prognosis".)

●(See "Bacterial meningitis in children: Neurologic complications".)

●(See "Bacterial meningitis in the neonate: Treatment and outcome".)

●(See "Bacterial meningitis in the neonate: Neurologic complications".)

DEXAMETHASONE

Rationale — Long-term neurologic sequelae (eg, hearing loss, cognitive impairment, motor disability) are common in survivors of bacterial meningitis, particularly patients with pneumococcal meningitis. These complications are as much a consequence of the host response to the infection as they are of the infection itself. (See "Bacterial meningitis in children: Neurologic complications" and "Pathogenesis and pathophysiology of bacterial meningitis".)

Animal studies suggest that hearing loss and other adverse neurologic outcomes may be related to the severity of the inflammatory response to meningeal infection [1-3]. These observations led to the evaluation of anti-inflammatory agents (most commonly, dexamethasone) as an adjunct to antimicrobial therapy in the treatment of bacterial meningitis. (See 'Efficacy' below.).

The theory is that anti-inflammatory therapy might reduce the risk of neurologic complications of bacterial meningitis by reducing inflammation and cerebral edema [4-11].

Considerations in decision-making — The decision to use dexamethasone in children with presumptive bacterial meningitis must be individualized. In addition to the potential benefits and adverse effects described below (see 'Efficacy' below and 'Adverse effects' below), factors to be weighed in this decision include:

●The likely pathogen (see 'Pathogen' below)

●The feasibility of administering dexamethasone before or at the same time as the first dose of antibiotic therapy (see 'Timing' below)

●The empiric antibiotic regimen (see 'Antibiotic regimen' below)

Pathogen — The efficacy of dexamethasone therapy appears to vary depending upon the pathogen. Dexamethasone is most effective in reducing hearing loss in children with Haemophilus influenzae type b (Hib) meningitis, which is a rare cause of bacterial meningitis in immunized children [12]. (See 'Efficacy' below.)

Experts continue to debate the efficacy of dexamethasone for children with meningitis caused by other organisms, including pneumococcus [13,14].

In clinical practice, it usually is not possible to know with certainty what the infecting pathogen is at the time of decision-making since dexamethasone should optimally be started at the same time as the first dose of antibiotic therapy. Thus, the clinician must make their best determination of what the likely pathogen is. Often, this determination relies on the results of the Gram stain or other rapid diagnostic test (eg, multiplex PCR testing). (See 'Pathogen-based approach' below.)

Timing — If dexamethasone is to be administered, it should optimally be given before or at the same time as the first dose of antibiotics. It is probably of no benefit if given more than one to two hours later, although this time interval has not been clearly defined [12,15,16].

Adjuvant dexamethasone may be less beneficial in children with delayed presentation to medical attention. Delay between onset of infection and initiation of appropriate antibiotic therapy may account for the relative lack of efficacy of dexamethasone in children from resource-limited versus resource-abundant countries and pneumococcal versus Hib meningitis [17,18]. (See 'Efficacy' below.)

In the Pediatric Multicenter Pneumococcal study on pneumococcal meningitis in eight children's hospitals from 2007 through 2013, dexamethasone was administered to 35 percent (n = 60) of 173 children; timely administration occurred in only 22 patients [19]. The 22 children who received dexamethasone in a timely manner did not differ from the 113 children who did not with respect to severity of illness or complications, including hearing loss.

Antibiotic regimen — The benefits of dexamethasone therapy may depend, in part, upon the empiric antibiotic regimen. Patients with possible penicillin-resistant pneumococcal meningitis are typically treated with vancomycin plus either ceftriaxone or cefotaxime, pending results of susceptibility testing. However, there is concern that the entry of vancomycin into the cerebrospinal fluid (CSF) could be reduced in patients who receive adjunctive dexamethasone [20-24].

These concerns are largely based on observations from experimental animal studies [20], and it is uncertain if the findings in animal studies apply to bacterial meningitis in humans. In two small clinical studies involving 9 children and 13 adults with pneumococcal meningitis who were treated with dexamethasone and vancomycin plus either ceftriaxone or cefotaxime, all patients achieved therapeutic vancomycin levels in the CSF [25,26].

Nevertheless, given the uncertainty, some experts suggest that if dexamethasone is administered, rifampin should be added to the empiric regimen [16]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

Pathogen-based approach — Our approach to adjunctive dexamethasone therapy is to base the decision upon the likely cause of meningitis. Common pathogens in pediatric bacterial meningitis are summarized in the table (table 1) and discussed in greater detail separately. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Microbiology'.)

However, in clinical practice, it usually is not possible to know with certainty what the infecting pathogen is at the time the decision is made (ie, before or at the same time as the first dose of antibiotic therapy). Thus, the clinician must make their best determination of what the likely pathogen is based on the child's age, immunization status, comorbidities, and results of rapid diagnostic tests (eg, Gram stain, multiplex PCR testing).

●Hib meningitis – For children in whom Hib is highly suspected as the cause of meningitis, we recommend adjunctive therapy with dexamethasone, provided that it can be administered before or at the same time as the first dose of antimicrobial therapy [27]. In clinical practice, this scenario is fairly uncommon since the causative organism usually is unknown at the time of the initial antibiotic dose. In addition, Hib is a rare cause of bacterial meningitis in immunized children. However, if results of the Gram stain (or other rapid diagnostic test) are readily available and suggest H. influenza, adjunctive therapy with dexamethasone is recommended. It is unknown if dexamethasone is beneficial for bacterial meningitis due to nontype b H. influenzae meningitis such as types a or f nontypeable, which are now more common than type b isolates causing invasive infections in children in the United States. (See "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Epidemiology'.)

●Other bacterial pathogens (pneumococcus, meningococcus, or unknown etiology) – For children with suspected pneumococcal or meningococcal meningitis, and those with presumptive bacterial meningitis of unknown etiology, the benefits of dexamethasone are less certain and the decision is individualized [14].

There is considerable practice variation regarding use of dexamethasone in this setting. The author of this topic does not routinely administer dexamethasone to children with presumptive meningitis due to pneumococcus, meningococcus, or other unspecified bacterial pathogen. Other experts may choose to use dexamethasone in this setting, particularly in young children (ie, ≥6 weeks to ≤5 years old) and children with sickle cell disease or hyposplenism. In addition, it is reasonable to use dexamethasone in older adolescent patients since it is a recommended component of therapy for adult patients with presumptive bacterial meningitis, as discussed separately. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'Adjunctive dexamethasone'.)

In a study of 173 children with pneumococcal meningitis treated in the United States from 2007 through 2013, 35 percent received dexamethasone [19].

●Nonbacterial or gram-negative enteric meningitis – Dexamethasone is not indicated in the treatment of patients with presumed aseptic, nonbacterial, or gram-negative enteric meningitis [16]. If dexamethasone is initiated before the diagnosis is made, it should be discontinued as soon as a diagnosis of nonbacterial or gram-negative enteric meningitis is confirmed.

●Young infants and patients with central nervous system anomalies – Dexamethasone is not indicated in the treatment of bacterial meningitis in young infants (<6 weeks old) or in those with congenital or acquired abnormalities of the central nervous system [16].

●Tuberculous meningitis – Glucocorticoid therapy appears to be beneficial in selected children and adults with tuberculous meningitis. This issue is discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Glucocorticoids'.)

Major society guidelines vary regarding guidance on adjunctive dexamethasone therapy in children with presumptive bacterial meningitis [14,16,27-29]. Guidelines from the American Academy of Pediatrics (AAP) and the Canadian Pediatric Society (CPS) recommend dexamethasone for pediatric patients with confirmed or suspected H. influenza meningitis, and they say dexamethasone "can be considered" in patients with presumptive pneumococcal meningitis [14,27,29]. In contrast, guidelines from the European Society of Clinical Microbiology and Infectious Diseases advise initiating dexamethasone in all cases of presumptive bacterial meningitis, though they advise discontinuing therapy if pathogens other than H. influenza or pneumococcus are identified [28]. Links to these and other society guidelines are provided separately. (See 'Society guideline links' below.)

Dose — If the decision is made to use dexamethasone, it should be given before or concurrently with the first dose of antibiotics. Appropriate dosing for dexamethasone in this setting is as follows:

●Dexamethasone (0.15 mg/kg per dose) given intravenously every six hours for two to four days [16]; a two-day course appears to be as effective as longer courses and is associated with a lower risk of adverse effects [30]. (See 'Adverse effects' below.)

Efficacy — The use of adjuvant dexamethasone in the treatment of pediatric bacterial meningitis has been studied in clinical trials, meta-analyses of clinical trials, and observational studies [12,15,31-46].

●Key findings from clinical trials – In a 2015 meta-analysis of 18 pediatric trials involving 2511 children with meningitis, mortality was similar in children treated with dexamethasone compared with placebo (13 versus 15 percent, respectively; relative risk [RR] 0.89; 95% CI 0.74-1.07) [12]. Severe hearing loss (generally defined as bilateral hearing loss of ≥60 decibels or requiring bilateral hearing aids) was less common in patients treated with dexamethasone (7 versus 11 percent; RR 0.67, 95% CI 0.49-0.97; 14 trials, 1524 patients). In subgroup analyses, the effect on hearing loss was largely limited to children with Hib meningitis (4 verses 12 percent; RR 0.34, 95% CI 0.20-0.59; 10 trials, 756 patients), whereas for other organisms, rates of severe hearing loss were similar in the dexamethasone and placebo groups (10 percent in both groups; RR 0.95, 95% CI 0.65-1.39; 13 trials, 860 patients). The incidence of short-term neurologic sequelae other than hearing loss was similar in both groups regardless of the causative organism (18 versus 20 percent; RR 0.90, 95% CI 0.72-1.13; 10 trials, 1271 patients).

●Limitations of the clinical trial data – In the available clinical trials, there was considerable heterogeneity with respect to the patient population (age, comorbidities, duration of preadmission symptoms, severity of illness), setting (resource-limited versus resource-abundant), and study interventions. Findings from studies in resource-limited countries may not be generalizable to resource-abundant settings, since delays in treatment are more common in resource-limited settings [47] and this likely impacts outcomes [17,48-50]. In particular, there were two trials from Malawi in which the mortality rates were three- to fivefold higher than in the studies from other countries [35,51], raising questions about the generalizability of these effect estimates [12,52]. Other factors that may contribute to increased mortality among patients from Malawi include poor nutrition and increased prevalence of HIV infection. Studies of dexamethasone in adolescents and adults in resource-limited settings are discussed separately. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'Adjunctive dexamethasone'.)

Another concern about the generalizability of these data is the era in which the trials were performed. Most of the trials included in the 2015 meta-analysis were published between 1988 and 1995, and the microbiology and treatment of bacterial meningitis have changed considerably since that time [42]. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Epidemiology'.)

With the widespread use of the Hib vaccine in developed countries, Streptococcus pneumoniae has become an increasingly important pathogen. However, many clinical trials studying dexamethasone were performed when Hib was the most frequent cause of bacterial meningitis [42,53]. Children with pneumococcal meningitis generally have a longer duration of fever before presentation compared with children with meningitis caused by other bacterial pathogens [18]. The delay between onset of infection and initiation of appropriate antimicrobial therapy may account for the apparent lack of efficacy of dexamethasone in children with pneumococcal compared with Hib meningitis [17].

In addition, few patients enrolled in the trials evaluating adjuvant dexamethasone were treated with vancomycin, which is now an important component of the empiric treatment for bacterial meningitis (because of the increased incidence of S. pneumoniae nonsusceptible to cephalosporins). The benefit of dexamethasone in patients with pneumococcal meningitis receiving vancomycin therapy is unclear, and there are concerns that dexamethasone may reduce vancomycin's entry into the CSF [54]. (See 'Antibiotic regimen' above and "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

●Observational data – In a retrospective study of 2780 children hospitalized for treatment of bacterial meningitis at 27 hospitals in the United States between January 2001 and December 2006 (ie, in the post-conjugate vaccine era), 9 percent received adjunctive glucocorticoid therapy [45]. The overall mortality rate was 4.2 percent, and mortality rates were similar in those who did or did not receive glucocorticoids (6 versus 4 percent, respectively; adjusted hazard ratio 1.09, 95% CI 0.53-2.24). The results did not change when analyzed according to infecting organism. Pneumococcus was the most commonly isolated pathogen in this study, accounting for 18 percent of cases, whereas H. influenza accounted for <5 percent.

Adverse effects — Potential adverse effects of dexamethasone include hyperglycemia, behavioral changes, and gastrointestinal effects (gastritis, peptic ulcer, gastrointestinal bleeding). However, most children tolerate short courses of dexamethasone well without serious adverse effects. Other side effects of systemic glucocorticoids are discussed separately. (See "Major adverse effects of systemic glucocorticoids".)

A particular downside of dexamethasone therapy in children with bacterial meningitis is that it can interfere with the ability of the clinician to assess clinical response to antibiotic therapy [16,55]. In addition, secondary fever (recurrence of fever after at least 24 hours without fever) may occur after discontinuation of dexamethasone [21].

Patients who receive adjuvant dexamethasone therapy do not appear to have slower clearance of bacteria from the CSF. However, children with meningitis who receive dexamethasone early in their course should be carefully observed throughout therapy. Because dexamethasone can interfere with the ability to interpret the clinical response, repeat LP is suggested in children who have received dexamethasone therapy [14]. This is discussed separately. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Repeat lumbar puncture'.)

The effects of dexamethasone on viral meningitis are not fully known; very few studies have examined the long-term outcome of children with viral meningitis who received dexamethasone at the time of presentation when bacterial meningitis was a consideration [56].

OTHER PROPOSED NEUROPROTECTIVE THERAPIES

Glycerol — Adjunctive glycerol therapy does not play a role in the management of pediatric bacterial meningitis in resource-abundant settings. While some studies suggest that adjunctive glycerol therapy may be beneficial in children with bacterial meningitis who are managed in low- and middle-income countries (LMIC), additional data are needed before it can be recommended as a routine in LMIC settings.

●Mechanism and rationale – Glycerol is an osmotic diuretic agent that has been used in neurosurgery, neurology, and ophthalmology to reduce intracranial or intraocular pressure [43,57-63]. In theory, it also may reduce meningeal inflammation by scavenging free oxygen radicals [43].

Adjunctive therapy with glycerol is appealing, particularly in LMICs, because it is widely available, orally administered, well tolerated, inexpensive, and does not require special storage [34,64,65].

●Supporting evidence – A 2018 meta-analysis of five trials involving 1272 patients with bacterial meningitis, glycerol had little to no effect on mortality (21 versus 19 percent; relative risk [RR] 1.08, 95% CI 0.9-1.30) [66]. However, glycerol was associated with a modest reduction in neurologic disability, a finding that was of borderline statistical significance (6 versus 9 percent; RR 0.73, 95% CI 0.53-1.0). In addition, glycerol reduced rates of hearing loss (10 versus 16 percent; RR 0.64, 95% CI 0.44-0.93). Four of the five trials included in the meta-analysis were performed in LMIC (two trials in Malawi, one in India, and one at multiple sites in South America).

Experimental therapies — The search for additional adjunctive agents that target inflammatory mediators has been an active area of investigation. The following agents have been studied (largely in animal models). These agents are experimental and are not routinely used in clinical practice.

●Antioxidants [67]

●Nitric oxide synthase inhibitors [68,69]

●Tumor necrosis factor-related apoptosis-inducing ligand [70]

●Melatonin [71]

●Caspase inhibitors [72]

●Adjunctive daptomycin and rifampin (antibiotics that are bacteriocidal but not bacteriolytic) [73-78]

●Roscovitine (which induces caspase-dependent apoptosis in neutrophils) [79]

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in infants and children".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Bacterial meningitis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Rationale – Anti-inflammatory agents (chiefly dexamethasone) have been proposed as an adjunct to antimicrobial therapy in the treatment of bacterial meningitis to reduce the inflammatory response, with the aim of preventing hearing loss and other neurologic complications. (See 'Rationale' above.)

●Clinical use of dexamethasone – In children with bacterial meningitis caused by Haemophilus influenzae type b (Hib), dexamethasone appears to reduce the risk of hearing loss. It is unclear if dexamethasone has similar benefit in patients with more common pathogens (eg, pneumococcus, meningococcus). Dexamethasone does not appear to reduce the risk of other neurologic sequelae. (See 'Efficacy' above.)

Our suggested approach is as follows (see 'Pathogen-based approach' above):

•Suspected Hib meningitis – For children with known or strongly suspected Hib meningitis (eg, on the basis of the Gram stain or other rapid diagnostic test), we recommend adjunctive therapy with dexamethasone, provided that it can be administered before or at the same time as the first dose of antimicrobial therapy (Grade 1B). In clinical practice, this scenario is uncommon. (See 'Pathogen-based approach' above and 'Efficacy' above.)

•Pneumococcal or meningococcal meningitis or unknown etiology – Practice varies regarding the use of dexamethasone in children with suspected pneumococcal or meningococcal meningitis or in patients with presumptive bacterial meningitis of unknown etiology. The author of this topic review does not routinely administer dexamethasone to children with suspected pneumococcal or meningococcal meningitis. In the same patients, other experts may choose to use dexamethasone. (See 'Pathogen-based approach' above.)

•Nonbacterial or gram-negative enteric meningitis – There is no role for adjunctive dexamethasone therapy in aseptic, nonbacterial, or gram-negative enteric meningitis. (See 'Pathogen-based approach' above.)

•Young infants and patients with central nervous system abnormalities – There is no role for adjunctive dexamethasone therapy in the treatment of bacterial meningitis in young infants (<6 weeks old) and in those with congenital or acquired abnormalities of the central nervous system. (See 'Pathogen-based approach' above.)

●Timing and dosing regimen – If dexamethasone is given, it should be administered before or at the same time as the first dose of antibiotics. It is probably of no benefit if given more than one hour later, although this time interval has not been clearly defined. (See 'Timing' above.)

Appropriate dosing for dexamethasone in this setting is 0.15 mg/kg per dose given intravenously every six hours for two to four days. (See 'Dose' above.)

  1. Bhatt SM, Lauretano A, Cabellos C, et al. Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry. J Infect Dis 1993; 167:675.
  2. Scheld WM, Dacey RG, Winn HR, et al. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone. J Clin Invest 1980; 66:243.
  3. Täuber 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.
  4. Sáez-Llorens X, Jafari HS, Severien C, et al. Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis. J Clin Invest 1991; 88:2003.
  5. 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.
  6. Kadurugamuwa JL, Hengstler B, Zak O. Cerebrospinal fluid protein profile in experimental pneumococcal meningitis and its alteration by ampicillin and anti-inflammatory agents. J Infect Dis 1989; 159:26.
  7. Mertsola J, Kennedy WA, Waagner D, et al. Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis. Am J Dis Child 1991; 145:1099.
  8. Mustafa MM, Ramilo O, Sáez-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.
  9. Lutsar I, Friedland IR, Jafri HS, et al. Factors influencing the anti-inflammatory effect of dexamethasone therapy in experimental pneumococcal meningitis. J Antimicrob Chemother 2003; 52:651.
  10. van Furth AM, Roord JJ, van Furth R. Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy. Infect Immun 1996; 64:4883.
  11. Ichiyama T, Matsushige T, Kajimoto M, et al. Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis. Brain Dev 2008; 30:95.
  12. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2015; :CD004405.
  13. Schaad UB, Kaplan SL, McCracken GH Jr. Steroid therapy for bacterial meningitis. Clin Infect Dis 1995; 20:685.
  14. American Academy of Pediatrics. Streptococcus pneumoniae (pneumococcal) infections. In: Red Book: 2024-2027 Report of the Committee on Infectious Diseases, 33rd ed, Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2024. p.810.
  15. King SM, Law B, Langley JM, et al. Dexamethasone therapy for bacterial meningitis: Better never than late? Can J Infect Dis 1994; 5:210.
  16. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
  17. Yogev R, Pelton S. To treat or not to treat is the nagging question. Pediatrics 2010; 125:e188.
  18. Bonsu BK, Harper MB. Fever interval before diagnosis, prior antibiotic treatment, and clinical outcome for young children with bacterial meningitis. Clin Infect Dis 2001; 32:566.
  19. Olarte L, Barson WJ, Barson RM, et al. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children. Clin Infect Dis 2015; 61:767.
  20. París MM, Hickey SM, Uscher MI, et al. Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1994; 38:1320.
  21. 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.
  22. Brady MT, Kaplan SL, Taber LH. Association between persistence of pneumococcal meningitis and dexamethasone administration. J Pediatr 1981; 99:924.
  23. Friedland IR, Paris M, Shelton S, McCracken GH. Time-kill studies of antibiotic combinations against penicillin-resistant and -susceptible Streptococcus pneumoniae. J Antimicrob Chemother 1994; 34:231.
  24. Moellering RC Jr. Pharmacokinetics of vancomycin. J Antimicrob Chemother 1984; 14 Suppl D:43.
  25. Klugman KP, Friedland IR, Bradley JS. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother 1995; 39:1988.
  26. Ricard JD, Wolff M, Lacherade JC, et al. Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study. Clin Infect Dis 2007; 44:250.
  27. American Academy of Pediatrics. Haemophilus influenzae infections. In: Red Book: 2024-2027 Report of the Committee on Infectious Diseases, 33rd ed, Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2024. p.400.
  28. van Ettekoven CN, van de Beek D, Brouwer MC. Update on community-acquired bacterial meningitis: guidance and challenges. Clin Microbiol Infect 2017; 23:601.
  29. Le Saux N, Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Guidelines for the management of suspected and confirmed bacterial meningitis in Canadian children older than one month of age. Paediatr Child Health 2014; 19:141.
  30. 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.
  31. 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.
  32. 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.
  33. Wald ER, Kaplan SL, Mason EO Jr, et al. Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group. Pediatrics 1995; 95:21.
  34. 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.
  35. Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 2002; 360:211.
  36. Qazi SA, Khan MA, Mughal N, et al. Dexamethasone and bacterial meningitis in Pakistan. Arch Dis Child 1996; 75:482.
  37. Ciana G, Parmar N, Antonio C, et al. Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis. J Trop Pediatr 1995; 41:164.
  38. Girgis NI, Farid Z, Mikhail IA, et al. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 1989; 8:848.
  39. Kanra GY, Ozen H, Seçmeer G, et al. Beneficial effects of dexamethasone in children with pneumococcal meningitis. Pediatr Infect Dis J 1995; 14:490.
  40. Lebel MH, Hoyt MJ, Waagner DC, et al. Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis. Am J Dis Child 1989; 143:301.
  41. Schaad UB, Lips U, Gnehm HE, et al. Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group. Lancet 1993; 342:457.
  42. 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.
  43. Peltola H, Roine I, Fernández J, et al. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2007; 45:1277.
  44. van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol 2010; 9:254.
  45. Mongelluzzo J, Mohamad Z, Ten Have TR, Shah SS. Corticosteroids and mortality in children with bacterial meningitis. JAMA 2008; 299:2048.
  46. Kameda S, Yamana H, Sasabuchi Y, et al. Early Corticosteroid Use and Short-Term Outcomes in Pediatric Bacterial Meningitis: A Nationwide Study in Japan, 2014 to 2022. Pediatr Neurol 2025; 164:97.
  47. Molyneux E, Riordan FA, Walsh A. Acute bacterial meningitis in children presenting to the Royal Liverpool Children's Hospital, Liverpool, UK and the Queen Elizabeth Central Hospital in Blantyre, Malawi: a world of difference. Ann Trop Paediatr 2006; 26:29.
  48. Lebel MH, Hoyt MJ, McCracken GH Jr. Comparative efficacy of ceftriaxone and cefuroxime for treatment of bacterial meningitis. J Pediatr 1989; 114:1049.
  49. Kaplan SL, Smith EO, Wills C, Feigin RD. Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis. Pediatr Infect Dis 1986; 5:626.
  50. McIntyre PB, Macintyre CR, Gilmour R, Wang H. A population based study of the impact of corticosteroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis. Arch Dis Child 2005; 90:391.
  51. Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 2007; 357:2441.
  52. McIntyre P. Adjunctive dexamethasone in meningitis: does value depend on clinical setting? Lancet Neurol 2010; 9:229.
  53. Prober CG. The role of steroids in the management of children with bacterial meningitis. Pediatrics 1995; 95:29.
  54. Kim KS. Bacterial meningitis beyond the neonatal period. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th, Cherry JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2019. p.309.
  55. Pelton SI, Yogev R. Improving the outcome of pneumococcal meningitis. Arch Dis Child 2005; 90:333.
  56. Waagner DC, Kennedy WA, Hoyt MJ, McCracken GH Jr. Lack of adverse effects of dexamethasone therapy in aseptic meningitis. Pediatr Infect Dis J 1990; 9:922.
  57. Singhi S, Järvinen A, Peltola H. Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis. Pediatr Infect Dis J 2008; 27:892.
  58. BUCKELL M, WALSH L. EFFECT OF GLYCEROL BY MOUTH ON RAISED INTRACRANIAL PRESSURE IN MAN. Lancet 1964; 2:1151.
  59. Gilsanz V, Rebollar JL, Buencuerpo J, Chantres MT. Controlled trial of glycerol versus dexamethasone in the treatment of cerebral oedema in acute cerebral infarction. Lancet 1975; 1:1049.
  60. Rottenberg DA, Hurwitz BJ, Posner JB. The effect of oral glycerol on intraventricular pressure in man. Neurology 1977; 27:600.
  61. Bayer AJ, Pathy MS, Newcombe R. Double-blind randomised trial of intravenous glycerol in acute stroke. Lancet 1987; 1:405.
  62. McCurdy DK, Schneider B, Scheie HG. Oral glycerol: the mechanism of intraocular hypotension. Am J Ophthalmol 1966; 61:1244.
  63. Zoghbi HY, Okumura S, Laurent JP, Fishman MA. Acute effect of glycerol on net cerebrospinal fluid production in dogs. J Neurosurg 1985; 63:759.
  64. Nau R, Prins FJ, Kolenda H, Prange HW. Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol. Eur J Clin Pharmacol 1992; 42:181.
  65. Tourtellotte WW, Reinglass JL, Newkirk TA. Cerebral dehydration action of glycerol. I. Historical aspects with emphasis on the toxicity and intravenous administration. Clin Pharmacol Ther 1972; 13:159.
  66. Wall EC, Ajdukiewicz KM, Bergman H, et al. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev 2018; 2:CD008806.
  67. Ge NN, Brodie SA, Tinling SP, Brodie HA. The effects of superoxide dismutase in gerbils with bacterial meningitis. Otolaryngol Head Neck Surg 2004; 131:563.
  68. Winkler F, Koedel U, Kastenbauer S, Pfister HW. Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood-brain barrier breakdown. J Infect Dis 2001; 183:1749.
  69. Boje KM. Inhibition of nitric oxide synthase attenuates blood-brain barrier disruption during experimental meningitis. Brain Res 1996; 720:75.
  70. Hoffmann O, Priller J, Prozorovski T, et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest 2007; 117:2004.
  71. Gerber J, Lotz M, Ebert S, et al. Melatonin is neuroprotective in experimental Streptococcus pneumoniae meningitis. J Infect Dis 2005; 191:783.
  72. Braun JS, Novak R, Herzog KH, et al. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 1999; 5:298.
  73. Grandgirard D, Schürch C, Cottagnoud P, Leib SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 2007; 51:2173.
  74. Spreer A, Lugert R, Stoltefaut V, et al. Short-term rifampicin pretreatment reduces inflammation and neuronal cell death in a rabbit model of bacterial meningitis. Crit Care Med 2009; 37:2253.
  75. Nau R, Wellmer A, Soto A, et al. Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis. J Infect Dis 1999; 179:1557.
  76. Böttcher T, Gerber J, Wellmer A, et al. Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis. J Infect Dis 2000; 181:2095.
  77. Gerber J, Pohl K, Sander V, et al. Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone. Antimicrob Agents Chemother 2003; 47:1313.
  78. Adjunction of daptomycin for the treatment of pneumococcal meningitis (AddaMAP). Clinical trial identifier NCT03480191. https://clinicaltrials.gov/study/NCT03480191 (Accessed on December 11, 2023).
  79. Koedel U, Frankenberg T, Kirschnek S, et al. Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog 2009; 5:e1000461.
Topic 6026 Version 35.0

References

1 : Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry.

2 : Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

3 : Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis.

4 : Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

5 : Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis.

6 : Cerebrospinal fluid protein profile in experimental pneumococcal meningitis and its alteration by ampicillin and anti-inflammatory agents.

7 : Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis.

8 : Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients.

9 : Factors influencing the anti-inflammatory effect of dexamethasone therapy in experimental pneumococcal meningitis.

10 : Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy.

11 : Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis.

12 : Corticosteroids for acute bacterial meningitis.

13 : Steroid therapy for bacterial meningitis.

14 : Steroid therapy for bacterial meningitis.

15 : Dexamethasone therapy for bacterial meningitis: Better never than late?

16 : Practice guidelines for the management of bacterial meningitis.

17 : To treat or not to treat is the nagging question.

18 : Fever interval before diagnosis, prior antibiotic treatment, and clinical outcome for young children with bacterial meningitis.

19 : Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children.

20 : Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

21 : Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use.

22 : Association between persistence of pneumococcal meningitis and dexamethasone administration.

23 : Time-kill studies of antibiotic combinations against penicillin-resistant and -susceptible Streptococcus pneumoniae.

24 : Pharmacokinetics of vancomycin.

25 : Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis.

26 : Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.

27 : Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.

28 : Update on community-acquired bacterial meningitis: guidance and challenges.

29 : Guidelines for the management of suspected and confirmed bacterial meningitis in Canadian children older than one month of age.

30 : Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen.

31 : The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.

32 : Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials.

33 : Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group.

34 : Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group.

35 : Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.

36 : Dexamethasone and bacterial meningitis in Pakistan.

37 : Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis.

38 : Dexamethasone treatment for bacterial meningitis in children and adults.

39 : Beneficial effects of dexamethasone in children with pneumococcal meningitis.

40 : Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis.

41 : Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group.

42 : Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988.

43 : Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.

44 : Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data.

45 : Corticosteroids and mortality in children with bacterial meningitis.

46 : Early Corticosteroid Use and Short-Term Outcomes in Pediatric Bacterial Meningitis: A Nationwide Study in Japan, 2014 to 2022.

47 : Acute bacterial meningitis in children presenting to the Royal Liverpool Children's Hospital, Liverpool, UK and the Queen Elizabeth Central Hospital in Blantyre, Malawi: a world of difference.

48 : Comparative efficacy of ceftriaxone and cefuroxime for treatment of bacterial meningitis.

49 : Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis.

50 : A population based study of the impact of corticosteroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis.

51 : Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.

52 : Adjunctive dexamethasone in meningitis: does value depend on clinical setting?

53 : The role of steroids in the management of children with bacterial meningitis.

54 : The role of steroids in the management of children with bacterial meningitis.

55 : Improving the outcome of pneumococcal meningitis.

56 : Lack of adverse effects of dexamethasone therapy in aseptic meningitis.

57 : Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis.

58 : EFFECT OF GLYCEROL BY MOUTH ON RAISED INTRACRANIAL PRESSURE IN MAN.

59 : Controlled trial of glycerol versus dexamethasone in the treatment of cerebral oedema in acute cerebral infarction.

60 : The effect of oral glycerol on intraventricular pressure in man.

61 : Double-blind randomised trial of intravenous glycerol in acute stroke.

62 : Oral glycerol: the mechanism of intraocular hypotension.

63 : Acute effect of glycerol on net cerebrospinal fluid production in dogs.

64 : Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol.

65 : Cerebral dehydration action of glycerol. I. Historical aspects with emphasis on the toxicity and intravenous administration.

66 : Osmotic therapies added to antibiotics for acute bacterial meningitis.

67 : The effects of superoxide dismutase in gerbils with bacterial meningitis.

68 : Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood-brain barrier breakdown.

69 : Inhibition of nitric oxide synthase attenuates blood-brain barrier disruption during experimental meningitis.

70 : TRAIL limits excessive host immune responses in bacterial meningitis.

71 : Melatonin is neuroprotective in experimental Streptococcus pneumoniae meningitis.

72 : Neuroprotection by a caspase inhibitor in acute bacterial meningitis.

73 : Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis.

74 : Short-term rifampicin pretreatment reduces inflammation and neuronal cell death in a rabbit model of bacterial meningitis.

75 : Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis.

76 : Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis.

77 : Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone.

78 : Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone.

79 : Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis.