Bacterial Meningitis

Wayne L. Gold, MD
Bacterial Meningitis: Objectives
To understand the limitations of the clinical
history/physical examination in the diagnosis of
bacterial meningitis
To understand the predictive value of initial CSF
investigations in the diagnosis of bacterial
meningitis
To understand the effect of prior antimicrobial
therapy on the interpretation of CSF laboratory
investigations
Bacterial Meningitis: Objectives
To be aware of the changing epidemiology and
microbiology of bacterial meningitis
To develop an approach to the empiric therapy of
the patient with suspected bacterial meningitis
To understand the benefits and risks of adjunctive
therapy with dexamethasone
Bacterial Meningitis: Case Presentation
43-year-old man
1-day-history of earache, headache
not able to be awakened in am
intubated for airway protection
ceftriaxone 2g iv in emergency room
Bacterial Meningitis: Case Presentation
Physical examination
Decreased level of consciousness
BP, 120/70 mmHg; HR, 120/minute
T = 41.0
o
C
Neck stiffness
Bacterial Meningitis: Case Presentation
CT scan normal
CSF investigations
Glucose 1.0 mmol/L (BS=10.4)
Protein 6.1 g/L
Leukocytes 11,720 X 10
6
/L
Bacterial Meningitis: Importance
Infectious disease emergency
Disease of young adults
Case-fatality rate remains high (~20%)
Long-term neurological morbidity
Bacterial Meningitis: Importance
Clinical signs and symptoms at presentation
may predict prognosis
Early recognition is important to allow
clinicians to efficiently complete
investigations
Goal: initiation of early antibiotic therapy
Does This Adult Patient
Have Acute Meningitis?
N = 10 studies
9 retrospective studies; 1 prospective study
pooled sensitivities for features of the clinical
history and physical examination reported
specificities are unavailable because control
groups without meningitis were not included in
most studies
Attia J. et al. JAMA 1999;282:175-81.
Does This Adult Patient
Have Acute Meningitis?
Clinical history:
Headache 50%
Nausea, vomiting 30%
Neck pain NA
Clinical history alone is not useful in establishing
diagnosis
Headache, nausea, vomiting are cardinal
symptoms of many diseases
Does This Adult Patient
Have Acute Meningitis?
Accuracy of physical examination
Fever 85%
Neck stiffness 70%
Altered mental status 67%
All three signs 46%
> 2 signs 95%
> 1 sign 99%
Does This Adult Patient
Have Acute Meningitis?
The Bottom Line
-the diagnosis of meningitis is virtually ruled out
in patients without any of these features (fever,
neck stiffness, altered mental status)
Does This Adult Patient
Have Acute Meningitis?
The Bottom Line
-Kernigs and Brudzinskis signs have low
sensitivity and specificity
-Jolt accentuation of headache
Sensitivity = 97%
Specificity = 60%
LR+ = 2.4
LR- = 0.05 (negative test virtually excludes dx)
Date of Onset
of Acute Meningitis
Does This Patient Require a
CT Scan of the Head Before LP?
Clinical Features Predictive of an
Abnormal CT Head
Age >60 years
Immunocompromised
host
History of CNS disease
Seizure within 1 week of
presentation
Altered level of
consciousness
Inability to answer 2
successive commands
Gaze palsy
Abnormal visual fields
Focal motor weakness
Aphasia/dysphasia
Hasbun R
NEJM 2001;345:1727-33.
CT Scan Before LP
in Suspected Meningitis?
Clinical features can be used to identify
adult patients unlikely to have abnormal CT
findings
Adults with these features should undergo
CT of the head prior to LP
Adults without these features are good
candidates for immediate lumbar puncture
Diagnosis of Acute Meningitis
Analysis of the Predictive Value
of Initial (Laboratory) Observations
Spanos A et al. JAMA 1989;262:2700-7.
Laboratory Predictors of
Acute Bacterial Meningitis (N=422)
Positive Gram-stain 71%
CSF glucose (< 2.8 mmol/L) 43%
CSF protein (> 0.45 g/L) 90%
CSF leukocytes (>100 X 10
6
/L) 85%
Acute bacterial meningitis
15% initial lymphocyte predominance
Acute viral meningitis
40% initial neutrophil predominance
30-40% of CSF findings are not diagnostic
Laboratory Predictors of
Acute Bacterial Meningitis (N=422)
Positive predictors: probability > 99%
Gram-stain +
CSF glucose < 1.9 mmol/L
CSF:blood glucose <0.23
CSF protein > 2.2 g/L (0.15-0.45 g/L)
CSF leukocytes > 2000 X 10
6
/L
CSF PMNs > 1180 X 10
6
/L
Accuracy of CSF Fluid Analysis
21 (14 32) CSF Lactate
>3.5 mmol/L
18 (12 27) Glucose Ratio
<0.4
23 (13 40) CSF Glucose
<2.2 mmol/L
15 (10 22) WBC
>500 X 10
6
/L
LR + CSF Test
Effect of Prior Treatment
on CSF Parameters (Partial Treatment)
Reduction in rates of positive gram-stains and
CSF cultures in patients who have received prior
antimicrobial therapy
CSF glucose, protein, leukocytes essentially
unchanged at 24h of therapy
Evidence from meningitis treatment trial where
repeat LPs were required to document sterilization
of CSF
no difference in CSF parameters between initiation of
therapy and follow-up LP at 24h
Schaad U et al NEJM 1990;322:141-7.
Empiric Treatment of
Suspected Bacterial Meningitis
Initial treatment decisions must be targeted
to the most likely microbial pathogens
Initial treatment must be based on
knowledge of local antimicrobial resistance
patterns
Bacterial Meningitis in the
United States in 1995 (N = 248)
Prior to the introduction of Hib conjugate
vaccines, bacterial meningitis was predominantly
a disease of infants (median age = 15 mo)
Since the introduction of vaccines, there has been
a 55% decline in all cases of meningitis
(95% reduction in cases of Hib meningitis)
Bacterial meningitis is now a disease
predominantly of adults (median age = 25 yr)
Schuchat A et al NEJM 1997;337:970-6.
Bacterial Meningitis in Toronto/Peel
(Population= 3,472,001)
Pathogen Incidence Case-fatality
S. pneumoniae 0.61/100,000/yr 15.3%
N. meningitidis 0.25/100,000/yr 7.4%
L. monocytogenes 0.12/100,000/yr 15.4%
H. influenza 0.07/100,000/yr
Group B streptococcus 0.20/100,000/yr
McGeer A
Toronto Invasive Bacterial Diseases Network.
Antimicrobial Resistance in
Streptococcus pneumoniae
Increasing prevalence of drug-resistant
pneumococci in Canada, United States
In bacterial meningitis, non-suspectibility of S.
pneumoniae to penicillin is of clinical importance
Canadian Bacterial Surveillance Network, Aug. 2003
Penicillin-Resistant Pneumococci: Canadian Bacterial
Surveillance Network, 1988-2002
0
2
4
6
8
10
12
14
16
1988 1993 1995 1997 1999 2001
% intermediate resistance
% high-level resistance
Bacterial Meningitis:
Drug Resistance
Reduced susceptibility to penicillin/
cephalosporins in S.pneumoniae have been
associated with treatment failures
Ceftriaxone stills retains susceptibility
against some PNSP at clinically achievable
levels in the CSF
Drug resistance has implications for
empiric antimicrobial therapy
Bacterial Meningitis:
Initial Empiric Therapy
Ceftriaxone 2g q12h
+Vancomycin 1g q12h
+/- Ampicillin 2g q4h
Bacterial Meningitis:
Duration of Therapy
Pathogen Duration of therapy (days)
S. pneumoniae 10-14
N. meningitidis 7
L. monocytogenes 14-21
H. influenzae 7
Quagliarello V, Scheld M NEJM 1997;336:708-16.
Adjuvant Therapy for
Bacterial Meningitis
Despite adequate antimicrobial therapy,
clinical outcomes remain poor:
Died during hospitalization 27%
Survived without deficit 65%
Survived with deficit 9%
Hearing loss 12%
Dexamethasone in Adults
with Bacterial Meningitis
RCT of adjuvant dexamethasome in adults with
acute bacterial meningitis
N=301 pts with turbid CSF:
dexamethasone 10 mg q6h X 4 days*
vs
placebo
*before or with first dose of antibiotics
Gans et al. N Engl J Med 2002;347:1549-56.
Dexamethasone in Adults
with Bacterial Meningitis
Outcomes:
-mortality
-neurologic morbidity (Glasgow Outcome Scale)
Dexamethasone in Adults
with Bacterial Meningitis
Glasgow Outcome Scale
1=death
2=vegetative state
3=severe disability*
4=moderate disability**
5=mild or no disability***
* unable to live independently
** able to live independently, unable to return to work
*** able to return to work
Dexamethasone in Adults
with Bacterial Meningitis
Unfavourable Outcome for S. pneumoniae:
Placebo: 52%
Dexamethasone: 26% (p=0.006)
Death for S. pneumoniae:
Placebo: 34%
Dexamethasone: 14% (p=0.02)
Dexamethasone in Adults
with Bacterial Meningitis
Unfavourable Outcome for All Organisms:
Placebo: 25%
Dexamethasone: 15% (p=0.03)
Death for All Organisms:
Placebo: 15%
Dexamethasone: 7 % (p=0.04)
Dexamethasone in Adults
with Bacterial Meningitis
The Bottom Line
early treatment with dexamethasone improves
outcomes in adults with acute bacterial meningitis with
turbid CSF
dexamethasone must be given before or with the first
dose of antibiotics
Dexamethasone in Adults
with Bacterial Meningitis
The Bottom Line
treatment effect is seen in patients with pneumococcal
meningitis
if meningitis is found not to be secondary to
pneumococci, consider discontinuing dexamethasone
dexamethasone does not increase the risk of
gastrointestinal bleeding
Bacterial Meningitis: Conclusions
Clinical history lacks accuracy in the
diagnosis of bacterial meningitis
The absence of fever, neck stiffness, and
altered level of consciousness virtually rule
out the diagnosis of bacterial meningitis
In certain circumstances, CSF biochemistry
may be diagnostic
Bacterial Meningitis: Conclusions
Recent changes in the epidemiology of bacterial
meningitis
Emergence of penicillin-resistant S. pneumoniae
has implications for the empiric treatment of
bacterial meningitis
Vancomycin + ceftriaxone should be used as
initial empiric therapy
Early adminstration of dexamethasone improves
outcomes in patients with pneumococcal
meningitis