View source for EBQ:De Gans - Steroids for Bacterial Meningitis

{{JC info
| title=Dexamethasone in Adults with Bacterial Meningitis
| abbreviation=EDS
| expansion=European Dexamethasone Study
| published=2002-11-14
| author=de Gans JD, et al
| journal=The New England Journal of Medicine
| year=2002
| volume=347
| issue=20
| pages=1549-1556
| pmid=12432041
| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa021334
| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa021334
| status=Complete
}}

==Clinical Question==
'''In patients with acute bacterial meningitis does dexamethasone improve outcomes when given in addition to standard antibiotic therapy?'''

==Conclusion==
'''Early treatment with dexamethasone in adults with acute bacterial meningitis improves outcomes, specifically neurologic sequalae in patient with Strep. Pneumonia [[Meningitis]] with no increase in GI Bleed'''

==Major Points==
*Dexamethasone may reduce the mortality of patients with S. pneumonia [[Meningitis]].  Specifically in the this study, patients with any of the following:
#Cloudy cerebrospinal fluid
#Bacteria in cerebrospinal fluid on Gram’s staining
#Cerebrospinal fluid leukocyte count of more than 1000/mL
were given an empiric 10mg of Dexamethasone 20min prior or during the first dose of antibiotic administration.  The goal was to both reduce mortality as well as neurologic sequelae. 

*The main benefit was demonstrated with the S. pneumonia meningitis group especially those with a GCS between 8-11. However the mortality benefits have not been replicated in non developed countries and there is concern for decreased CSF penetration of antibiotics.  Regardless there is a demonstrated benefit to decreased hearing loss and short term neurologic sequelae with a NNT of 21 to prevent hearing loss<ref>The NNT - Steroids in bacterial meningitis http://www.thennt.com/nnt/steroids-for-meningitis/</ref>

'''*The Infectious Disease Society of America recommends the use of dexamethasone in all patients with suspected Strep. Pneumoniae meningitis. <ref>Tunkel AR et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267</ref> and continuation of the dexamethasone as an in-patient can be based on the culture and gram stain results of the CSF'''

==Study Design==
Prospective, randomized, double-blinded, multi-center, controlled trial

==Population==
*N=301; randomly assigned to 1 of 2 groups
**157 in dexamethasone group
**144 in placebo group

===Patient Demographics===
{|class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Group Characteristic'''
| align="center" style="background:#f0f0f0;"|'''Dexamethasone'''
| align="center" style="background:#f0f0f0;"|'''Placebo'''
|-
| Age (yr)||44+/-18||46+/-20
|-
| Bacteria + in gram stain of CSF||74%||69%
|-
| CSF WBC >1000/gram stain neg||24%||29%
|-
| Cloudy CSF only||2%||2%
|-
| Duration of symp prior to admission(median)||24||24
|-
| Seizures||10%||5%
|-
| CSF opening pressure||37+/-13||34+/-14
|-
| GCS (median)||12||12
|-
| Papilledema||7%||10%
|-
| CN palsy||9%||12%
|-
| Hemiparesis||6%||8%
|-
| CSF Strep Pneumo||37%||35%
|-
| CSF Nisseria||32%||33%
|-
| CSF other||8%||12%
|-
| CSF negative||24||24
|-
| CSF WBC (mean)||8185||7438
|-
| CSF Protein||4.3+/-3.0||4.7+/-3.2
|-
| CSF Glucose||27+/-31||27+/-29
|-
| Blood Cx +||53%||47%
|}

===Inclusion Criteria===
*Age 17 yrs or older AND
*Suspected meningitis with:
**Cloudy CSF OR
**Bacteria in CSF on gram stain OR
**CSF leukocyte count >1000
 
===Exclusion Criteria===
*Hypersensitivity to B-lactam antibiotics or steroids
*Pregnancy
*Cerebrospinal shunt
*Treatment with antibiotics within past 48 hours
*Active TB or fungal infection
*Recent head trauma, neurosurgery, or PUD
*Enrollment in other trial

==Interventions==
*Randomized to receive Dexamethasone or placebo
**Interventions looked identical and were blinded from provider and patient
**Given 15-20 min prior to antibiotics, but amended to allow simultaneous administration of antibiotics and intervention after interim analysis
**10 mg IV q6 hrs x 4 days of Dexamethasone sodium or placebo
*Initially treated with amoxicillin 2 g IV q4 x7-10 days
**Antibiotic was changed according to susceptibility if needed

==Outcomes==
*Analyzed with an intention to treat analysis and last-observation-carried-forward procedure

===Primary Outcome===
*Glasgow Outcome Scale 8 weeks after intervention
**Score of 5 = favorable outcome
**Score of 1-4 = unfavorable outcome
***Dexamethasone: 15%
***Placebo: 25% 
:p value = 0.03
:CI 0.37–0.94
:RR 0.59

===Secondary Outcomes=== 
*Death
**Dexamethasone: 7%
**Placebo: 15% 
:p value = 0.04
:CI 0.24–0.96
:RR 0.48 

*Focal neurological abnormalities
**Dexamethasone: 13%
**Placebo: 20% 
:p value = 0.13
:CI 0.36–1.09
:RR 0.62 

*Hearing loss
**Dexamethasone: 9%
**Placebo: 12% 
:p value = 0.54
:CI 0.38–1.58
:RR 0.77 

*GI bleed
**Dexamethasone: 2 patients
**Placebo: 5 patients
:p value = 0.27
*Fungal infection
:p value = 0.24
*Herpes Zoster
:p value = 0.75
*Hyperglycemia
:p value = 0.38

===Subgroup analysis===
*Causes of meningitis
**Streptococcus pneumoniae
**Neisseria meningitidis
**Other bacteria
**Culture negative CSF
*Statistically significant decrease in GOS unfavorable outcomes and death with dexamethasone in strep pneumo subgroup
*No other subgroup reached statistical significance

==Criticisms & Further Discussion==
{{Steroids Bacterial Meningitis}}

==Funding==
Supported in part by a grant from NV Organon, which also supplied the study medication.

==Sources==
<references/>


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