Your activity: 2 p.v.

Dexamethasone to prevent neurologic complications of bacterial meningitis in adults

Dexamethasone to prevent neurologic complications of bacterial meningitis in adults
Author:
Daniel J Sexton, MD
Section Editor:
Allan R Tunkel, MD, PhD, MACP
Deputy Editor:
Jennifer Mitty, MD, MPH
Literature review current through: Dec 2022. | This topic last updated: May 19, 2021.

INTRODUCTION — Bacterial meningitis continues to result in substantial morbidity and mortality despite the availability of effective antimicrobial therapy. The risk of dying or of developing complications is related to the age and general health of the patient, the causative pathogen, the severity and duration of illness at the time of presentation, and, occasionally, delays in the initiation of antibiotic therapy. (See "Initial therapy and prognosis of bacterial meningitis in adults".)

Early intravenous administration of glucocorticoids (usually dexamethasone) has been evaluated as adjuvant therapy in an attempt to diminish the rate of hearing loss and other neurologic complications as well as mortality in selected patients with bacterial meningitis. The possible protective role of dexamethasone therapy to prevent neurologic complications in selected adult patients will be reviewed here. The neurologic complications of meningitis in adults and more general issues, such as the clinical manifestations, diagnosis, treatment, and prognosis of bacterial meningitis in adults as well as neurologic complications and the role of dexamethasone in neonates and children with bacterial meningitis, are discussed separately. (See "Neurologic complications of bacterial meningitis in adults" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Bacterial meningitis in the neonate: Neurologic complications" and "Bacterial meningitis in children: Neurologic complications" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications".)

COMPLICATIONS OF BACTERIAL MENINGITIS — Complications due to bacterial meningitis can be divided into systemic and neurologic. Systemic complications such as septic shock, disseminated intravascular coagulation, acute respiratory distress syndrome, and septic or reactive arthritis are usually the consequence of the bacteremia that frequently accompanies meningitis [1].

The neurologic complications of bacterial meningitis include:

Impaired mental status

Increased intracranial pressure and cerebral edema

Seizures

Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis)

Cerebrovascular abnormalities

Sensorineural hearing loss

Intellectual impairment

These complications may be sudden or gradual in onset and can appear at any time after the onset of symptoms, including after the completion of therapy. Although many neurologic complications are severe, others such as hearing loss may be subtle or inapparent during the early phases of infection. (See "Neurologic complications of bacterial meningitis in adults".)

RATIONALE — Early intravenous administration of glucocorticoids (usually dexamethasone) has been evaluated as adjuvant therapy in an attempt to diminish the rate of hearing loss and other neurologic complications as well as mortality in selected patients with bacterial meningitis. The rationale for this approach is provided by animal studies showing that hearing loss is temporally associated with the severe inflammatory changes induced by bacterial meningitis [2] and that dexamethasone reduces cerebrospinal fluid (CSF) concentrations of cytokines (such as tumor necrosis factor [TNF]-alpha and interleukin [IL]-1), CSF inflammation, and cerebral edema [3-6]. (See "Neurologic complications of bacterial meningitis in adults", section on 'Sensorineural hearing loss'.)

In a randomized trial of patients in Vietnam with bacterial meningitis, those who received adjunctive dexamethasone had lower CSF opening pressures, higher CSF:plasma glucose ratios, and lower CSF concentrations of the cytokines IL-6, IL-8, and IL-10 compared with patients who received placebo [7].

STUDIES — Clinical trials of adjuvant dexamethasone therapy for bacterial meningitis have been performed in both developed and developing countries with inconsistent results. An additional issue is the possible effect of such therapy on the penetration of antibiotics into the cerebrospinal fluid (CSF).

In developed regions — The efficacy of dexamethasone in adults with bacterial meningitis in the developed world was best evaluated in a randomized trial in 301 patients from Europe with bacterial meningitis [8]. The median duration of symptoms prior to treatment was 24 hours. All patients had suspected meningitis in combination with one or more of the following findings on CSF analysis: cloudy fluid, a positive Gram stain for bacteria (seen in 74 percent), and/or a CSF white blood cell count above 1000/microL. CSF culture revealed Streptococcus pneumoniae in 36 percent, Neisseria meningitidis in 32 percent, other bacteria in 10 percent, and no bacteria in 21 percent.

The patients were randomly assigned to intravenous dexamethasone (10 mg every six hours for four days) or placebo with the first dose administered 15 to 20 minutes before or at the time of antibiotic administration [8]. Most patients were initially treated with intravenous amoxicillin as a single agent, and no pneumococcal isolates resistant to penicillin were detected among the 78 of 108 isolates upon which susceptibility testing was performed. The primary endpoint was all unfavorable outcomes (death or neurologic disability) at eight weeks. Secondary outcomes were focal neurologic deficits, hearing loss, and side effects of dexamethasone therapy, such as gastrointestinal bleeding, fungal infection, herpes zoster, and hyperglycemia.

The following findings were noted at eight weeks [8]:

Dexamethasone significantly reduced both mortality (7 versus 15 percent with placebo, relative risk [RR] 0.48, 95% CI 0.24-0.96) and all unfavorable outcomes (15 versus 25 percent, RR 0.59, 95% CI 0.37-0.94).

When the outcomes were analyzed based upon culture results (S. pneumoniae, N. meningitidis, other bacteria, or negative bacterial culture), significant reductions in mortality (14 versus 34 percent) and all unfavorable outcomes (26 versus 52 percent) were only seen with dexamethasone therapy in patients with S. pneumoniae meningitis. Patients who did not have pneumococcal meningitis (most often meningococcal meningitis) had much lower rates of both mortality (4 percent) and all unfavorable outcomes (9 percent), independent of whether or not they received dexamethasone therapy. (See "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Mortality'.)

Among the patients with pneumococcal meningitis, significant benefit was seen only in those with an intermediate neurologic deficit on admission, defined as a Glasgow coma scale of 8 to 11 (table 1). In such patients, the rate of unfavorable outcomes at eight weeks was reduced in the dexamethasone group (22 versus 52 percent, RR 0.43, 95% CI 0.19-0.95). There was no evidence of benefit among patients with a mild neurologic deficit.

In a subset analysis of patients with pneumococcal meningitis, the mortality benefit seen with dexamethasone was entirely due to reduced mortality from a systemic cause such as septic shock, pneumonia, or acute respiratory distress syndrome (2 versus 16 percent without dexamethasone); there was no significant reduction in mortality due to neurologic causes (7 versus 10 percent) [9].

There was no increase in gastrointestinal bleeding with dexamethasone therapy.

A follow-up study at a median of over eight years evaluated the long-term effects of dexamethasone on neurologic sequelae in 87 of 99 eligible patients [10]. There was no difference between the treatment groups with regard to persistent cognitive dysfunction, hearing loss, or focal neurologic deficits. It is possible that the trial was underpowered to detect benefits of this magnitude. In addition, these neurologic sequelae primarily occurred in the most severely ill patients; the proportion of patients who survived to be tested was significantly greater in the dexamethasone group.

An additional finding was that patients with pneumococcal meningitis had a significantly higher rate of persistent cognitive dysfunction compared with other patients (21 versus 6 percent) [10]. This observation is consistent with the worse outcomes at eight weeks cited above in the patients with pneumococcal meningitis [8].

A separate follow-up study with median follow-up of 13 years evaluated long-term survival in 228 of 246 evaluable patients [11]. Overall, 31 of 144 patients (22 percent) in the dexamethasone group died, compared with 44 of 134 patients (33 percent) in the placebo group. After the primary outcome measurement at eight weeks, an additional 20 patients in the dexamethasone group and 23 patients in the placebo group died, and age was the sole predictor of death. These results suggest that the survival benefit of dexamethasone is obtained during the acute phase of the disease and that there are no differences at later time points.

A nationwide prospective cohort study was undertaken in the Netherlands to evaluate the implementation of adjunctive dexamethasone use in adults with pneumococcal meningitis [12]. Dexamethasone was initiated with or before the first dose of antibiotics in 84 percent of 357 patients with pneumococcal meningitis in 2006 to 2009 but in only 3 percent of 352 patients in 1998 to 2002. At hospital discharge, an unfavorable outcome (defined as Glasgow outcome scale score of 1 to 4 points) was present in 39 percent of patients in the 2006 to 2009 cohort compared with 50 percent of patients in the 1998 to 2002 cohort (odds ratio [OR] 0.63, 95% CI 0.46-0.86). Rates of death (20 versus 30 percent) and hearing loss (12 versus 22 percent) were significantly lower in the 2006 to 2009 cohort.

In a subsequent prospective cohort study of adult patients with community-acquired bacterial meningitis in the Netherlands from 2006 to 2014, adjunctive dexamethasone treatment was given in 1234 of 1384 episodes (89 percent) [13]. In a multivariate analysis, use of dexamethasone given to patients according to guideline recommendations was associated with a significantly lower rate of adverse outcomes (OR 0.54, 95% CI 0.39-0.79) and lower mortality (OR 0.46, 95% CI 0.32-0.66).

A study compared data regarding the use of dexamethasone in adults with meningococcal meningitis from two prospective cohort studies of community-acquired bacterial meningitis in the Netherlands; the first study enrolled 258 patients between 1998 and 2002, before routine dexamethasone therapy was introduced, and the second study enrolled 100 patients between 2006 and 2011, after guidelines recommended dexamethasone [14]. Dexamethasone was administered to 17 percent of patients in the 1998 to 2002 cohort and 90 percent of patients in the 2006 to 2011 cohort and was continued in the majority of patients after N. meningitidis was identified by culture. In the later (dexamethasone) cohort compared with the earlier cohort, there was a nonsignificant trend toward a reduction in hearing loss (3 versus 8 percent) and death (4 versus 11 percent). Similar Glasgow outcome scores were observed in the two cohorts. The rate of arthritis was significantly lower in the later cohort compared with the earlier cohort (32 of 258 patients [12 percent] versus 5 of 96 [5 percent]). These results suggest that the use of dexamethasone in patients with meningococcal meningitis is not associated with harm and that there may be small yet unproven benefits.

A population-based observational study using data from the Healthcare Cost Utilization Project database found that both the incidence and mortality rates of pneumococcal meningitis declined among American patients between 1997 and 2010 [15]. Overall incidence rates of pneumococcal meningitis declined from 0.8 to 0.3 per 100,000 people over this time period, a decrease of 63 percent. Rates of death from pneumococcal meningitis also declined from 0.073 people per 100,000 from 2002 to 2004 to 0.049 per 100,000 people from 2005 to 2008. The authors attributed the decline in mortality to the introduction of guidelines promoting the use of adjunctive dexamethasone therapy, although their analysis did not include data on the actual use of such therapy.

In developing regions — In contrast with the results of the above trial, which involved patients with bacterial meningitis in the developed world, a study from sub-Saharan Africa found no benefit from treatment with dexamethasone [16]. In this randomized trial of adults in Malawi, 465 patients (90 percent of whom were HIV infected) received dexamethasone or placebo for four days plus intravenous or intramuscular ceftriaxone.

In an intention-to-treat analysis, there was no significant mortality difference at 40 days in the dexamethasone group as compared with the placebo group (56 versus 53 percent, OR 1.14, 95% CI 0.79-1.64). There was also no difference in mortality when the analysis was restricted to patients with pneumococcal meningitis (53 versus 50 percent, OR 1.10; 95% CI 0.68-1.77), and there were no significant differences between the two groups in the outcomes of disability and death combined, hearing loss, and adverse events.

There are several issues that must be considered in the interpretation of these results. In Malawi, the outcomes of bacterial meningitis are poor and the life expectancy is low. Contributing factors to worse outcomes in these patients include poor nutrition, delays in presentation that may have contributed to neurologic compromise prior to treatment, and chronic diseases such as HIV.

A similar prospective, randomized, double-blind trial of 435 Vietnamese patients (of whom less than 1 percent were HIV infected) found no overall reduction in mortality or disability with dexamethasone therapy compared with placebo started before the first dose of antibiotics (intravenous ceftriaxone) [17]. However, when the analysis was limited to the 300 patients (69 percent) with confirmed bacterial meningitis (ie, those with organisms cultured from CSF or blood or detected in CSF), there was a significant reduction in the risk of death at one month (RR 0.43; 95% CI 0.20-0.94) and in the risk of death or disability at six months (OR 0.56; 95% CI 0.32-0.98). The major causes of confirmed bacterial meningitis were Streptococcus suis (39 percent), S. pneumoniae (18 percent), N. meningitis (6 percent), and other gram-negative organisms (10 percent). The outcomes were significantly worse in patients with confirmed meningitis caused by a bacterium other than S. suis, who had a mortality rate of 2.6 percent. The median duration of symptoms prior to therapy was three to four days in this study cohort.

Patients who received dexamethasone for probable bacterial meningitis (defined as the presence of a typical clinical picture and lack of an alternative diagnosis in the absence of identification of bacteria in CSF or blood) had an increased risk of death at one month. The authors proposed that this finding could be explained by the inadvertent inclusion of cases of tuberculous meningitis. Eleven individuals in the study (eight in the dexamethasone group and three in the placebo group) were subsequently treated for tuberculous meningitis on clinical grounds. Six of these patients died, all of whom had received dexamethasone. Similar adverse effects of dexamethasone were seen in Ethiopian patients who were treated for presumed bacterial meningitis [18,19].

Meta-analyses — Several meta-analyses have been performed using data collected in various randomized controlled trials of glucocorticoid treatment of bacterial meningitis [20-22]. The latest of these studies was a 2015 Cochrane meta-analysis that included data from 4121 individual patients entered into 25 randomized trials [22]. The patient populations in the trials analyzed were heterogeneous (children and adults, developing world and developed world). This meta-analysis showed the following findings:

There was no difference in mortality between patients who received glucocorticoids and those who did not, although there was a nonsignificant trend toward decreased mortality in adults who received glucocorticoids (RR 0.74, 95% CI 0.53-1.05). In subgroup analyses that evaluated high-income countries and low-income countries separately, no mortality benefit was observed in either group.

A subgroup analysis showed that glucocorticoids reduced mortality in patients with meningitis caused by S. pneumoniae (RR 0.84, 95% CI 0.72-0.98) but not in meningitis caused by Haemophilus influenzae or N. meningitidis.

Glucocorticoids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51-0.88), any hearing loss (RR 0.74, 95% CI 0.63-0.87), and short-term neurologic sequelae other than hearing loss (RR 0.83, 95% CI 0.69-1.00). There was no difference in long-term neurologic sequelae between glucocorticoid-treated patients and controls (RR 0.90, 95% CI 0.74-1.10). In a subgroup analysis for study quality, glucocorticoids had no effect on severe hearing loss in high-quality studies.

In high-income countries, glucocorticoids reduced severe hearing loss (RR 0.51, 95% CI 0.35-0.73), any hearing loss (RR 0.58, 95% CI 0.45-0.73), and short-term neurologic sequelae (RR 0.64, 95% CI 0.48-0.85). In contrast, in low-income countries, glucocorticoids conferred none of these beneficial effects.

Glucocorticoids were associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09-1.47) but not with other adverse events, including clinically evident gastrointestinal tract bleeding, reactive arthritis, pericarditis, herpes zoster or herpes simplex infection, fungal infection, and persistent fever.

This meta-analysis suggests that glucocorticoids reduce mortality only in patients with S. pneumoniae meningitis. It also suggests that glucocorticoids reduce hearing loss and short-term neurologic sequelae among patients in high-income countries but not among patients in low-income countries.

Effect on antibiotic regimen — There is a potential problem with the use of dexamethasone in patients with possible penicillin- and cephalosporin-resistant pneumococcal meningitis. Such patients are typically treated with vancomycin plus ceftriaxone pending susceptibility results. However, the entry of vancomycin into the CSF may be reduced by the decrease in inflammation with dexamethasone.

This issue was addressed in a rabbit model of penicillin- and cephalosporin-resistant pneumococcal meningitis [23]. Dexamethasone substantially reduced the penetration of vancomycin into the CSF, resulting in a delay in CSF sterilization that was not seen in rabbits not treated with dexamethasone. In comparison, rifampin penetration into the CSF was not affected by dexamethasone, and the combination of rifampin and ceftriaxone produced prompt bacteriologic cure.

The applicability of these experimental findings in rabbits to bacterial meningitis in humans is uncertain. Therapeutic CSF concentrations of vancomycin in the CSF were evaluated in a study of 14 adults with bacterial meningitis, 13 of whom had pneumococcal meningitis who were treated with dexamethasone and vancomycin (15 mg/kg loading dose followed by a continuous infusion of 60 mg/kg per day in adults) plus ceftriaxone or cefotaxime [24]. The mean CSF vancomycin concentration was 7.9 mcg/mL (range 3.1 to 22.3 mcg/mL), which is higher than the minimum inhibitory concentration (MIC) of vancomycin for S. pneumoniae (0.25 to 1.0 mcg/mL) [25].

The CSF vancomycin concentrations were directly related to the serum vancomycin concentrations, suggesting that high doses of vancomycin are required to achieve effective CSF vancomycin concentrations [24]. However, it is not certain how the findings with a constant vancomycin infusion used in this study apply to the more common regimen of two to four divided daily doses. Furthermore, since there was no control group, this study did not address the issue of whether dexamethasone interferes with vancomycin penetration into the CSF.

Appropriate initial dosing of vancomycin is discussed separately. (See "Treatment of bacterial meningitis caused by specific pathogens in adults", section on 'First-line regimens' and "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)

The choice of antibiotic regimen in patients with bacterial meningitis who are treated with dexamethasone is described below. (See 'Antibiotic regimens' below.)

THERAPEUTIC APPROACH — The efficacy of dexamethasone therapy in patients with bacterial meningitis varies in developed and developing countries and with the offending organism.

Developed regions — In developed regions, we recommend administration of dexamethasone to all adults with suspected bacterial meningitis in whom the organism is not yet known. Dexamethasone should only be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S. pneumoniae. Based upon data reported in the large randomized trial cited above [8] as well as the 2015 meta-analysis [22], dexamethasone therapy is appropriate in adults in developed countries with known or suspected pneumococcal meningitis and a Glasgow coma scale score of 8 to 11 (table 1) [8]. However, the 2004 Infectious Diseases Society of America (IDSA) guidelines for the management of bacterial meningitis recommend that adjunctive dexamethasone be initiated in all adults with suspected or proven pneumococcal meningitis, regardless of the Glasgow coma scale, because assessment of the Glasgow coma scale score may delay the initiation of appropriate therapy [25]. We agree with the guidelines; however, since the etiology of bacterial meningitis is not usually known at the time of treatment initiation, and S. pneumoniae is the most common cause of bacterial meningitis in adults in developed regions, we extend the recommendation to the larger population of patients with suspected bacterial meningitis.

Dexamethasone should be continued for four days if the Gram stain reveals organisms consistent with S. pneumoniae or if the cerebrospinal fluid (CSF) or blood culture grows S. pneumoniae. By contrast, dexamethasone should be discontinued if the Gram stain and/or cultures reveal another pathogen or if bacterial meningitis is subsequently thought not to be present. There is no proven benefit from dexamethasone therapy for adult patients with meningitis due to other pathogens, mostly meningococcus [8], but also including gram-negative bacilli [26] (see "Gram-negative bacillary meningitis: Treatment"). In addition, in a prospective cohort study of patients with neurolisteriosis, adjunctive dexamethasone was associated with reduced survival [27]; however, the number of treated patients was small.

The recommended intravenous dexamethasone regimen is 0.15 mg/kg every six hours for four days [25]. Dexamethasone should be initiated shortly before or at the same time as the first dose of antibiotics. In a review that included 118 episodes of community-acquired bacterial meningitis in adults in which dexamethasone was given, the likelihood of an unfavorable outcome was much higher in the 94 patients in whom dexamethasone was given after antibiotics (51 versus 12 percent if given before antibiotics) [28]. Thus, we suggest that adjunctive dexamethasone NOT be given to adults who have already received antimicrobial therapy because it is unlikely to improve patient outcomes.

Developing regions — The benefit of dexamethasone in developing regions is less clear than for developed countries. In regions with high HIV prevalence, high rates of malnutrition, and delayed clinical presentation such as Africa, there does not appear to be any clinical benefit to the administration of dexamethasone [16,29]. In other regions, we suggest administering dexamethasone in patients who have bacterial meningitis confirmed by Gram stain or a rapid diagnostic test [17,29]. We suggest the regimen used in the Vietnamese trial (0.4 mg/kg every 12 hours for four days) starting before the first dose of antibiotics. In some areas of the developing world, however, it is not possible to get microbiologic test results in a prompt fashion. Thus, empirically administering adjunctive dexamethasone is reasonable in patients in whom there is a strong clinical suspicion for acute bacterial meningitis until microbiologic results are available. Dexamethasone should only be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S. pneumoniae.

Antibiotic regimens — Given the uncertainty of the magnitude of the effect of dexamethasone on the CSF penetration of vancomycin, there are two reasonable therapeutic options when adults with confirmed or possible pneumococcal meningitis are treated with dexamethasone [25]. (See 'Effect on antibiotic regimen' above.)

Begin with a regimen of vancomycin plus either ceftriaxone or cefotaxime. If susceptibility studies show intermediate susceptibility or resistance (minimum inhibitory concentration [MIC] ≥1 mcg/mL) to ceftriaxone and cefotaxime, rifampin is added if the organism is susceptible [25].

The rationale for this regimen is that vancomycin penetration into the CSF starts at a high level in the presence of bacterial meningitis and that impairment in penetration to a level that will reduce efficacy is not likely in the first few days before susceptibility studies are available.

Begin with a regimen of vancomycin plus ceftriaxone or cefotaxime plus rifampin pending studies of susceptibility. A potential problem with rifampin therapy is the induction of hepatic CYP isoenzymes, thereby increasing the metabolism of a variety of drugs. (See "Rifamycins (rifampin, rifabutin, rifapentine)", section on 'Drug interactions'.)

The dosing of the agents in these regimens is discussed separately. (See "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults".)

Tuberculous meningitis — Glucocorticoid therapy may also be beneficial in selected adults and children with tuberculous meningitis. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Glucocorticoids'.)

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 adults".)

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 e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (See "Patient education: Bacterial meningitis (The Basics)".)

SUMMARY AND RECOMMENDATIONS — Early intravenous administration of glucocorticoids (usually dexamethasone) has been evaluated as adjuvant therapy in an attempt to diminish the rate of hearing loss and other neurologic complications as well as mortality in selected patients with bacterial meningitis. The efficacy of dexamethasone therapy has been reported to vary in developed and developing countries. (See 'Studies' above.)

When indicated, dexamethasone is given 15 to 20 minutes before or at the time of antibiotic administration. Two-dose regimens are recommended: 0.15 mg/kg every six hours for four days in the developed world, based upon the Infectious Diseases Society of America guidelines, and 0.4 mg/kg every 12 hours for four days in the developing world, based upon the Vietnamese trial. Adjunctive dexamethasone should not be given to adults who have already received antimicrobial therapy because it is unlikely to improve patient outcomes. (See 'Therapeutic approach' above.)

For adults in the developed world with suspected bacterial meningitis in whom the organism is not yet known, we recommend administration of dexamethasone (Grade 1B). Dexamethasone should only be continued if the cerebrospinal fluid (CSF) Gram stain and/or the CSF or blood cultures reveal Streptococcus pneumoniae. (See 'In developed regions' above and 'Developed regions' above.)

In areas of the developing world where there is a high prevalence of HIV infection, poor nutrition, and significant delays in clinical presentation, such as some regions of Africa, it is unlikely that the use of adjunctive dexamethasone will be of benefit. Thus, for adults in such regions with known or suspected bacterial meningitis, we recommend not administering dexamethasone (Grade 1B). In other regions of the developing world, we suggest administering dexamethasone in patients who have bacterial meningitis confirmed by Gram stain or a rapid diagnostic test (Grade 2B). It is also reasonable to empirically administer adjunctive dexamethasone in patients in whom there is a strong clinical suspicion for acute bacterial meningitis until microbiologic results are available. (See 'In developing regions' above and 'Developing regions' above.)

In patients with known or suspected pneumococcal meningitis who are treated with dexamethasone, we suggest adding rifampin to the standard antibiotic regimen (vancomycin plus either ceftriaxone or cefotaxime) if susceptibility studies show intermediate susceptibility or resistance (minimum inhibitory concentration [MIC] ≥1 mcg/mL) to ceftriaxone and cefotaxime (Grade 2C). A reasonable alternative is to include rifampin as part of the initial regimen and then discontinue it if the isolate is susceptible to the cephalosporin. (See 'Antibiotic regimens' above.)

  1. Pfister HW, Feiden W, Einhäupl KM. Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Arch Neurol 1993; 50:575.
  2. 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.
  3. Freyer D, Manz R, Ziegenhorn A, et al. Cerebral endothelial cells release TNF-alpha after stimulation with cell walls of Streptococcus pneumoniae and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine loops. J Immunol 1999; 163:4308.
  4. 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.
  5. 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.
  6. 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.
  7. Mai NT, Tuan TV, Wolbers M, et al. Immunological and biochemical correlates of adjunctive dexamethasone in Vietnamese adults with bacterial meningitis. Clin Infect Dis 2009; 49:1387.
  8. de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549.
  9. van de Beek D, de Gans J. Dexamethasone and pneumococcal meningitis. Ann Intern Med 2004; 141:327.
  10. Weisfelt M, Hoogman M, van de Beek D, et al. Dexamethasone and long-term outcome in adults with bacterial meningitis. Ann Neurol 2006; 60:456.
  11. Fritz D, Brouwer MC, van de Beek D. Dexamethasone and long-term survival in bacterial meningitis. Neurology 2012; 79:2177.
  12. Brouwer MC, Heckenberg SG, de Gans J, et al. Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis. Neurology 2010; 75:1533.
  13. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, et al. Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2016; 16:339.
  14. Heckenberg SG, Brouwer MC, van der Ende A, van de Beek D. Adjunctive dexamethasone in adults with meningococcal meningitis. Neurology 2012; 79:1563.
  15. Castelblanco RL, Lee M, Hasbun R. Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study. Lancet Infect Dis 2014; 14:813.
  16. 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.
  17. Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med 2007; 357:2431.
  18. Gudina EK, Tesfaye M, Adane A, et al. Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking? BMC Neurol 2016; 16:153.
  19. Gudina EK, Tesfaye M, Wieser A, et al. Outcome of patients with acute bacterial meningitis in a teaching hospital in Ethiopia: A prospective study. PLoS One 2018; 13:e0200067.
  20. van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 2004; 4:139.
  21. 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.
  22. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2015; :CD004405.
  23. 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.
  24. 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.
  25. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
  26. Chaudhuri A. Adjunctive dexamethasone treatment in acute bacterial meningitis. Lancet Neurol 2004; 3:54.
  27. Charlier C, Perrodeau É, Leclercq A, et al. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 2017; 17:510.
  28. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004; 351:1849.
  29. Greenwood BM. Corticosteroids for acute bacterial meningitis. N Engl J Med 2007; 357:2507.
Topic 1299 Version 36.0

References