Treating Bacterial Meningitis in Adults: Should Adjunctive Steroids be Used?
Treating Bacterial Meningitis in Adults: Should Adjunctive Steroids be Used?
Authors: Michael T. Fitch, MD, PhD, Assistant Professor of Emergency Medicine, Neuroscience Program Faculty, Wake Forest University School of Medicine, Winston-Salem, NC; and Heather M. Barnett, MD, Resident Physician, Department of Emergency Medicine, Wake Forest University Baptist Medical Center, Winston-Salem, NC.
Peer Reviewer: Ian Grover, MD, Assistant Clinical Professor of Medicine, UCSD Medical Center, San Diego, CA.
Introduction
Even with rapid diagnosis and initiation of treatment, bacterial meningitis continues to be a major cause of morbidity and mortality in adult patients. Mortality rates for this neurological emergency vary between 13% and 27%, even with adequate and timely antibiotic therapy.1,2 Controversies remain regarding the diagnosis and treatment of bacterial meningitis.3,4 Animal studies have shown that treatment with antibiotics induces bacterial lysis, which causes inflammation within the subarachnoid space;5,6 this can cause detrimental clinical effects within the confined spaces of the brain and spinal cord. In particular, central nervous system (CNS) inflammation in response to meningitis can produce elevated intracranial pressure, glial scarring, seizures, and permanent neurological disabilities.
Using pharmacologic agents to combat this unwanted inflammatory response in the CNS is an area of active investigation. One adjunctive agent that has been well-studied in recent years is corticosteroids, used to limit inflammation in conjunction with appropriate antimicrobial agents.7 Are corticosteroids beneficial for reducing the morbidity and mortality associated with meningitis? Do the potential side effects and risks outweigh the benefits? Furthermore, do glucocorticoids alter CNS penetration of antibiotics as suggested in animal models? This article will discuss the recent literature and recommendations on adjunctive steroid treatment in acute bacterial meningitis in adults.
Does Adjunctive Steroid Treatment Improve Outcomes in Bacterial Meningitis?
Source: 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;347:1549-1556.
The european dexamethasone Study is the largest prospective, randomized, double-blind, multicenter trial of adult patients with bacterial meningitis who were treated with dexamethasone compared with placebo. This study from the Netherlands included 301 adults, randomized to either the dexamethasone group (157 patients) or the placebo group (144 patients). Both groups were treated with amoxicillin (2 g IV every 4 hours) for 7 to 10 days, with any changes in regimen guided by the causative pathogen and clinical response to therapy. Study medication was given either 15-20 minutes prior to treatment with an antimicrobial agent or, after protocol amendment, in conjunction with the antibiotics. In the dexamethasone group, dexamethasone sodium phosphate was administered at a dose of 10 mg IV every 6 hours for 4 days. Patients in the control group received placebo that was similar in appearance to the active study drug at the same dosing schedule.
Inclusion criteria included that the patients were age 17 or older with suspected bacterial meningitis as defined by: cloudy cerebrospinal fluid (CSF); bacteria in CSF on Gram's stain; or a CSF leukocyte count of more than 1000 per cubic millimeter. Those excluded from the study were patients with hypersensitivity to corticosteroids or beta-lactam antibiotics, pregnancy, cerebrospinal shunt, previous treatment with antibiotics within 48 hours, history of active tuberculosis or fungal infection, recent head trauma, recent neurosurgery, peptic ulcer disease, or enrollment in another trial. The primary outcome measure was a favorable versus an unfavorable outcome using the Glasgow Outcome Scale (GOS) 8 weeks after randomization. A favorable outcome was based on a GOS score of 5. Unfavorable outcomes were any score between 1 and 4 (1=death, 2=vegetative state, 3=severe disability, 4=moderate disability, 5=mild or no disability). Secondary outcome measures were death, focal neurologic abnormalities, hearing loss, gastrointestinal bleeding, fungal infection, herpes zoster, and hyperglycemia.
Results eight weeks after enrollment demonstrated that the percentage of patients with an unfavorable outcome in the dexamethasone group (15%) was significantly smaller than in the placebo group (25%), with a relative risk of 0.59 (95% confidence interval [CI], 0.37-0.94; p=0.03). This difference was statistically significant. The absolute reduction in the risk of unfavorable outcome was 10%. The proportion of patients who died was significantly smaller in the dexamethasone group than in the placebo group (7% vs. 15%; relative risk, 0.48; 95% CI, 0.24-0.96; p=0.04). Secondary outcome measures with the use of adjunctive dexamethasone did not find statistically significant benefits for neurologic sequelae such as hearing loss. Treatment with dexamethasone did not result in an increased risk of adverse events, including gastrointestinal bleeding (see Table 1).
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Commentary
This is a very well designed multicenter trial, and represents the largest study to date examining the use of adjunctive steroids in the treatment of bacterial meningitis in adult patients. The primary outcome is clinically relevant, and the choice to compare a favorable outcome on the GOS (score of 5) versus anything other than favorable (scores of 1-4) is very compelling for the potential benefit of this treatment. The overall reduction in mortality provides additional rationale for the use of dexamethasone in conjunction with appropriate antimicrobial therapy.
Interestingly, despite the benefits seen with steroid treatment, the use of dexamethasone did not lead to any significant difference in the number of survivors who had neurological sequelae, including hearing loss. One possible explanation is that steroid treatment does not alter the development of all types of neurological deficits. However, as these were secondary outcomes in this study there may not have been a sufficient number of patients to detect all differences. It should be noted that a higher proportion of severely ill patients survived in the dexamethasone group, where neurological sequelae are more prominent; this may be the reason a significant difference was not found for specific neurologic deficits.
The enrollment criteria for this prospective study led to a patient population with evidence of bacterial meningitis (cloudy CSF, positive CSF Gram's stain, or CSF white blood cell count > 1000 per cubic millimeter), which was appropriate for the goals of this study. However, this population may not necessarily reflect all patients in whom the diagnosis of meningitis is suspected in the emergency department, as many patients initially suspected of bacterial meningitis will subsequently be diagnosed with viral meningitis or other alternative diagnoses. Therefore, in an undifferentiated population of patients with suspected meningitis for whom CSF results are not yet available, this study population may differ in some characteristics.
In addition to the beneficial effects demonstrated for patients with bacterial meningitis who are treated with dexamethasone, the results reported in this study are reassuring that the dosing regimen used here does not lead to an increase in steroid-related side effects. There were no significant differences in the rates of gastrointestinal bleeding or other adverse events. Steroids are, therefore, recommended for all adults with suspected bacterial meningitis when initiating empiric antibiotic therapy.
Does Steroid Treatment for Meningitis Lead to Long-Term Cognitive Impairment?
Source:Weisfelt M, Hoogman M, van de Beek D, et al. Dexamethasone and long-term outcome in adults with bacterial meningitis. Ann Neurol 2006;60:456-468.
Multiple studies have shown evidence of corticosteroid damage to certain areas of the brain related to learning and memory. With the recent recommendations to treat acute bacterial meningitis in adults with adjunctive dexamethasone, the risks of possible long-term cognitive impairment secondary to this steroid treatment is of interest to clinicians treating CNS infections. Previous in vitro studies have suggested that corticosteroids are toxic to cultured hippocampal and cortical neurons; animal studies have demonstrated that striatal and hippocampal neurons are vulnerable to dexamethasone, which may cause hippocampal apoptosis in bacterial meningitis. Concern thus exists for possible permanent neuropsychological side effects for patients treated for bacterial meningitis with adjunctive corticosteroids.
This study was a follow-up study of the European Dexamethasone Study previously discussed.8 Adults who survived pneumococcal or meningococcal meningitis underwent neurologic, audiologic, and neuropsychologic testing a median of 99 months after meningitis. Eighty-seven of 99 eligible patients who had survived bacterial meningitis were evaluated; 46 of those patients had been treated with dexamethasone and 41 with placebo. The control group included an additional 50 subjects who were recruited for testing. Neuropsychological examination was performed on all patients and control subjects with various testing modalities, including questionnaires, audiological examination, and several different psychological tests such as the Boston Naming Test and Dutch Adult Reading Test. Test scores were categorized as impaired if results were at least two standard deviations below the mean score of the control group, after correction for age and education. Further, cognitive dysfunction was considered to be present if performance, reflected by the number of impaired test results, was worse than the fifth percentile of the control group.
Results of this study showed that 13% of all patients who survived bacterial meningitis had cognitive impairment. Patients surviving pneumococcal meningitis were at higher risk, as 21% suffered cognitive impairments that mainly consisted of memory deficits. Overall, there were no statistically significant differences between patients treated with or without dexamethasone for bacterial meningitis.
Commentary
Possible long-term side effects are one concern for patients who receive steroid therapy for bacterial meningitis. This secondary breakdown of the large European Dexamethasone Study allowed long-term analysis of 87 patients to assess for residual effects. Limitations of this study include the design as a secondary analysis of a larger study whose primary outcomes were not related to neuropsychological side effects, and the small number of participants enrolled who were more likely to include those with higher Glasgow Outcome Scale scores (favorable outcome in 80 of 87 patients; Glasgow Outcomes Scale=5). A significant strength of this analysis is that the median length of time for testing was more than 8 years after surviving meningitis; therefore, these findings do represent a long-term assessment of function in these patients. This study lends support to the idea that the use of steroid therapy as an adjunctive treatment for meningitis does not lead to worsened neuropsychiatric outcomes.
Does Steroid Treatment Reduce CSF Antibiotic Penetration?
Source: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;44:250-255.
Streptococcus pneumoniae is the most common cause of bacterial meningitis, and treatment guidelines support the use of vancomycin in addition to a third generation cephalosporin to treat this pathogen. The penetration of vancomycin across the blood brain barrier is limited by its hydrophilic properties, and the degree of meningeal inflammation directly impacts its concentration in the CSF. The theoretical possibility that adjunctive treatment with dexamethasone could decrease this meningeal inflammation and irritation and, therefore, decrease vancomycin penetration into the CSF has been proposed. Does treatment with steroids lead to a significant decrease in vancomycin levels in the CSF?
Ricard et al performed a prospective, multicenter, observational study to evaluate levels of vancomycin in CSF in adult patients receiving adjunctive corticosteroids. They followed 14 adult patients who were admitted to the ICU with suspected pneumococcal meningitis who were treated with IV cefotaxime (200 mg/kg per day), vancomycin (15 mg/kg loading dose followed by 60 mg/kg/day continuous infusion) and dexamethasone (10 mg every 6 hours). Inclusion criteria required patients to be older than age 18 and that they were hospitalized in one of the 4 participating Paris-area hospitals with proven or suspected pneumococcal meningitis, with repeat lumbar punctures on day 2 or 3. One of the centers also used rifampin. Once susceptibilities were obtained, appropriate antibiotic regimens were tailored. On day 2 or 3, repeat lumbar puncture was performed to assess treatment success. At that time, serum and CSF vancomycin levels were simultaneously obtained.
Results showed all strains of pneumococcus (13/14 patients; one patient with meningococcal disease) were susceptible to vancomycin. The vancomycin MIC for S. pneumoniae was obtained for 10 patients and was found to be 0.125-1 mg/L. The mean concentration for serum vancomycin was 25.2 mg/L and the mean concentration for CSF vancomycin was 7.9 mg/L, with a significant correlation (r=0.68, p=0.01). All patients demonstrated levels above the desired MIC and had negative CSF cultures on repeat lumbar puncture, as well as a marked improvement in all CSF parameters. Appropriate concentrations of vancomycin were found in the CSF even when steroids were used, and the penetration of vancomycin into the CSF was correlated with the levels in the serum.
Commentary
This study addresses a very important question that has been raised about the use of anti-inflammatory agents for CNS infections, such as steroids, as adjunctive treatment for meningitis. If the penetration of antibiotics is adversely affected by the decrease in inflammation that is the desired effect of steroid treatment, this could theoretically interfere with the effectiveness with which bacterial pathogens are killed in the CSF. The strength of this study is limited by a small sample size of only 14 patients, and the observational design that included no control group; also, no conclusions can be drawn about whether steroid treatment leads to decreased levels of vancomycin in the CSF as compared to antibiotic treatment in the absence of adjunctive steroids. Another notable issue to consider is that the dosing regimen used in this study for vancomycin, which included a continuous infusion, is higher than what is typically used in the United States. Additional studies may be required to confirm these findings, but this study suggests that the use of dexamethasone does not prevent adequate penetration of vancomycin in the CSF of patients with bacterial meningitis.
Is the Risk of Cognitive Deficits Increased in Patients Treated with Steroids for Meningitis?
Source: Hoogman M, van de Beek D, Weisfelt M, et al. Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry 2007;78:1092-1096.
Many patients who survive bacterial meningitis still have significant cognitive impairments to overcome. These impairments involve memory, attention, executive function, psychomotor function, and intelligence. These kinds of cognitive functions are very difficult to test even in an ideal situation, and differences in assessment methods and definitions of impairment can make it difficult for clinicians to make conclusions about survivors of meningitis and their risks for long-term deficits. This manuscript pooled cognitive outcomes data from three previous studies to more clearly ascertain which cognitive functions are at risk of impairment in these patients.
Three long-term follow-up studies embedded in two research databases were pooled. The data come from the European Dexamethasone Study (EDS)8 and the Dutch Meningitis Cohort.1 The EDS was a randomized, double-blind, placebo-controlled study of adjunctive dexamethasone therapy in adults with bacterial meningitis. The full trial included 301 patients, and 87 of those patients participated in an additional study on cognitive outcomes with long-term follow-up, as discussed above in the article by Weisfelt et al in 2006.9 The Dutch Meningitis Cohort was a prospective, observational, cohort study of adults with bacterial meningitis, which included two follow-up studies on neuropsychological outcomes. Sixty-eight patients with meningitis (41 pneumococcal and 27 meningococcal) were assessed and compared against healthy control subjects. Standardized neuropsychological tests were used to evaluate memory, attention/executive functions, psychomotor function, and intelligence. The patient data from these three long-term studies were pooled, and cognitive impairment was considered to be present if performance was worse than the fifth percentile of the control group.
A total of 155 adults (79 pneumococcal meningitis and 76 meningococcal meningitis) were pooled from these three previous studies and compared to 72 healthy controls. Patients with meningitis had significant differences from control groups in attention/executive function and psychomotor function, but no differences in memory or intelligence. The frequency of cognitive impairment was 37% in pneumococcal and 28% in meningococcal meningitis. These data were further analyzed to look for possible differences in cognitive impairment with and without adjunctive dexamethasone therapy, and no significant difference was found between patients who had received and those who had not received steroid treatment.
Commentary
This study incorporates data discussed in the previous article by Weisfelt et al9 and, therefore, shares some of the same identified limitations. Pooling individuals from three trials (two databases) of patients with meningitis allowed for a larger sample size in this analysis, thus addressing one of the limitation previously discussed. Coming to consensus on what is considered a significant cognitive impairment can be difficult, and this can be further clouded by concerns of uniform testing methods and/or variability in the definitions of impairment. By the nature of the type of cognitive testing that is completed, patients with very severe disabilities may be unable to even present for such testing; this would limit the enrollment to patients who had more favorable outcomes. This post hoc analysis of a small subset of patients surviving bacterial meningitis was not designed to have sufficient power to make definitive conclusions about whether treatment with dexamethasone leads to long-term deficits more frequently than not treating with dexamethasone. However, with this limitation in mind it is reassuring that no significant differences were found in those patients who were treated with steroids.
How Do Steroids Influence Risk of Death in Pneumococcal Meningitis?
Source: Weisfelt M, van de Beek D, de Gans J. Dexamethasone treatment in adults with pneumococcal meningitis: risk factors for death. Eur J Clin Microbiol Infect Dis 2006;25:73-78.
With recent studies demonstrating that Streptococcus pneumoniae is the most common cause of bacterial meningitis, there has been increased interest in more carefully studying the population of patients with streptococcal meningitis. The overall results of the European Dexamethasone Study (EDS) supported treatment with dexamethasone to improve outcomes for patients with meningitis.8 This post hoc analysis of the data from this trial focused on the 112 patients with pneumococcal meningitis. Sixty patients had been treated with adjunctive dexamethasone and 52 had received placebo. A multivariate logistic regression analysis was used to determine risk factors for death in patients with pneumococcal disease.
The absence of dexamethasone therapy was one of several independent risk factors for patient death that was identified with this analysis. Other predictors of patient mortality were advanced age (p=0.03), tachycardia (p=0.02), low GCS score (p=0.03), absence of dexamethasone therapy (p=0.05), and positive blood cultures (p=0.04). The patients who were treated with dexamethasone were less likely to develop systemic complications such as cardiorespiratory failure and sepsis (22% vs. 50%; OR=0.43, 95% CI 0.25-0.75; p=0.002), and also were less likely to develop neurologic complications such as seizures (7% vs. 31%, p=0.002).
Commentary
This post hoc analysis from the EDS provides some valuable information about patients with the most common cause of bacterial meningitis, S. pneumoniae. Most of the independent risk factors that were identified as significant by multivariate logistic regression analysis are beyond the control of treating physicians: advanced age, tachycardia, low GCS score, and positive blood cultures. The one risk factor that clinicians can control that was found to be significant is the use of adjunctive steroids in the treatment regimen. This highlights the importance of the overall results in the original EDS trial supporting dexamethasone for patients being treated for meningitis, and provides additional guidance about initiating steroid therapy as an intervention that can be provided by the treating physician to potentially influence patient outcomes.
Does a Systematic Review of Multiple Trials Support Treatment with Adjunctive Steroids?
Source: van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2007(1):CD004405.
This cochrane database systematic Review is a meta-analysis of published and non-published randomized controlled trials of corticosteroids versus placebo as adjuvant therapy in acute bacterial meningitis. A total of 18 studies of adults and children were included (2750 people). Primary outcome measures evaluated were overall mortality, severe hearing loss, and neurologic sequelae. Additional subanalyses were performed to evaluate children and adults, causative organisms, and low-income versus developed countries.
The primary outcomes of this analysis revealed that steroid treatment led to lower mortality (relative risk [RR] 0.83; 95% CI, 0.71-0.99), with mortality rates reduced from 21.7% to 11.7%. Other primary outcomes found less hearing loss (RR 0.65; 95% CI, 0.47-0.91) and reduced neurological sequelae (RR 0.67; 95% CI, 0.45-1.00) for patients treated with steroids. The secondary analyses found reduced mortality for all patients with S. pneumoniae and reduced hearing loss for children with H. influenzae. Interestingly, for children in low-income countries the use of steroids did not demonstrate beneficial effects in the treatment of bacterial meningitis.
Commentary
The strength of this meta-analysis that was completed as a Cochrane Database review is the large number of patients included. Using randomized controlled trials with a combined total of 2750 adults and children, the favorable outcomes illustrated here give further support to the use of adjunctive steroids for the treatment of bacterial meningitis in adults and children. While adult patients are the primary focus of this current issue of Practical Summaries in Acute Care, it is notable to point out that the continued controversy in the pediatric literature regarding this topic is fueled in part by studies from non-industrialized countries where the benefits of steroid treatment for meningitis are unclear.10 It is, therefore, interesting that the overall results in this meta-analysis for the secondary outcome of steroids for the treatment of pediatric patients found that children in low-income countries did not appear to derive the same benefits as other patient populations. However, the other populations examined (children from high-income countries and adults from high- or low-income countries) did demonstrate improved outcomes with steroid therapy. Therefore, treatment guidelines support the use of steroids as an adjunctive therapy for these patient populations.
Have Practice Guidelines Incorporated Recommendations for Steroid Treatment?
Source:Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-1284.
Practice guidelines provided by expert panels and specialty societies are one way medical treatment recommendations can be standardized based on available evidence. The Infectious Diseases Society of America (IDSA) published its most recent practice guideline for the management of bacterial meningitis in 2004.11 This article covers many aspects of the diagnosis and treatment of meningitis, and includes several specific recommendations about the use of adjunctive dexamethasone. After reviewing and discussing the 5 trials on adjunctive dexamethasone in adults with bacterial meningitis that were available at the time these guidelines were formulated, the IDSA guidelines incorporated the use of adjunctive steroids in the treatment recommendations.11
- "... we recommend the use of dexamethasone (0.15 mg/kg q6h for 2-4 days with the first dose administered 10-20 min before, or at least concomitant with, the first dose of antimicrobial therapy) in adults with suspected or proven pneumococcal meningitis."11
- "Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to improve patient outcome."11
- "... adjunctive dexamethasone should be administered to all adult patients with pneumococcal meningitis, even if the isolate is subsequently found to be highly resistant to penicillin and cephalosporins."11
Commentary
The first two of the recommendations quoted above from the most recent treatment guidelines published by the IDSA were given A-I grades, indicating "good evidence to support a recommendation for use; should always be offered" based on "evidence from > 1 properly randomized, controlled trial." The third recommendation listed above was given a B-III grade, indicating "moderate evidence to support a recommendation for use; should generally be offered" based on "evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees." It is notable that these practice guidelines focus on the use of steroids for patients with pneumococcal meningitis, as the data from available studies is strongest for this pathogen, and steroids are not recommended if antibiotics have already been administered. This provides support for initiating the steroids at the time of antibiotic administration, when the causative pathogen for the suspected meningitis is unknown and could be S. pneumoniae. Providers in the emergency department or other acute care areas should be familiar with these guidelines so that adjunctive steroids can be considered at the time of initial empiric antibiotic therapy.
Summary
Acute bacterial meningitis is an uncommon but severe neurologic emergency that continues to cause significant morbidity and mortality in affected patients even with appropriate antimicrobial therapy. The search for adjunctive therapies for this illness continues, and the use of dexamethasone as an anti-inflammatory agent has been the best studied pharmacologic agent for this purpose. Questions about the efficacy of this treatment, potential side effects associated with its use, and concerns about long-term outcomes have been potential barriers to the routine use of dexamethasone along with appropriate antibiotics in patients with bacterial meningitis.
As detailed in this review, adjunctive dexamethasone treatment improves patient outcomes in adults with acute bacterial meningitis without increasing side effects such as gastrointestinal bleeding, fungal infections, fevers, or herpes infections. Clinical outcomes studies suggest no increase in long-term neuropsychological side effects or cognitive impairments from this treatment. Concerns about the effective penetration of antibiotics into the CSF in the setting of steroids do not appear to be significant, at least in one small study. Systematic reviews with a meta-analysis of the data and recent practice guidelines support the use of steroids as an adjunctive treatment for patients with suspected bacterial meningitis. Current guidelines are to initiate dexamethasone therapy just before or in conjunction with appropriate empiric antibiotic therapy, and the recommended dosing regimen is 10 mg intravenously every 6 hours for 4 days.
References
1. van de Beek D, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004;351:1849-1859.
2. Weisfelt M, et al. Clinical features, complications and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 2006;5:123-129.
3. Fitch MT, van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis 2007;7:191-200.
4. Fitch MT, et al. Emergency department management of meningitis and encephalitis. Infect Dis Clin North Am 2008;22:33-52.
5. Scheld WM, et al. Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J Infect Dis 2002;186(Suppl 2):S225-233.
6. Tauber MG, Sande MA. General principles of therapy of pyogenic meningitis. Infect Dis Clin North Am 1990;4:661-676.
7. Fitch MT, van de Beek D. Drug Insight: steroids in CNS infectious diseasesnew indications for an old therapy. Nat Clin Pract Neurol 2008;4:97-104.
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;347:1549-1556.
9. Weisfelt M, et al. Dexamethasone and long-term outcome in adults with bacterial meningitis. Ann Neurol 2006;60:456-468.
10. Molyneux EM, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 2002;360:211-218.
11. Tunkel AR, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-1284.
Even with rapid diagnosis and initiation of treatment, bacterial meningitis continues to be a major cause of morbidity and mortality in adult patients. Mortality rates for this neurological emergency vary between 13% and 27%, even with adequate and timely antibiotic therapy.Subscribe Now for Access
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