MENINGITIS

Bacterial
Viral ( aseptic)
TB
Fungal
Chemical
Parasitic
? Carcinomatous

MENINGITIS
Definition
Bacterial meningitis is an inflammatory response
to bacterial infection of the pia-arachnoid and CSF
of the subarachnoid space

Epidemiology
Incidence is between 3-5 per 100,000
Relative frequency of bacterial species varies with
age.

MENINGITIS
Epidemiology
Neonates (< 1 Month)
Gm (-) bacilli 50-60%
Grp B Strep 20-40%
Listeria sp. 2-10%
H. influenza 0-3%
S. pneumo 0-5%

MENINGITIS
Epidemiology
Children (1 month to 15 years)
H. influenzae

40-60%

Declining dramatically in many geographic regions

N. meningitidis 25-40%
S. pneumo
10-20%

MENINGITIS
Epidemiology
Adults (> 15 years)
S. pneumo
N. Meningitidis

30-50%
10-35%

Major cause in epidemics

Gm (-) Bacilli 1-10%

Elderly

S. aureus
H. influenzae 1-3%

5-15%

>60 years age include Listeria, E. coli, Pseudomonas

MENINGITIS
Pathogenesis
Majority of cases are hematogenous in
origin
Organisms have virulence factors that allow
bypassing of normal defenses
Proteases
Polysaccharidases

MENINGITIS
Pathology and Pathogenesis
Sequential steps allow the pathogen into the CSF

Nasopharyngeal colonization
Nasopharyngeal epithelial cell invasion
Bloodstream invasion
Bacteremia with intravascular survival
Crossing of the BBB and entry into the CSF
Survival and replication in the subarachnoid space

MENINGITIS
Pathology
Hallmark
Exudate in the subarachnoid space
Accumulation of exudate in the dependent areas of the
brain
Large numbers of PMNs
Within 2-3 days inflammation in the walls of the small
and medium-sized blood vessels
Blockage of normal CSF pathways and blockage of the
normal absorption may lead to obstructive
hydrocephalus

MENINGITIS
Clinical Manifestations
HA
Fever
Meningismus
Cerebral dysfunction
Confusion, delirium, decreased level of consciousness

N/V
Photophobia

MENINGITIS
Clinical Manifestations Nuchal rigidity
Kernigs
Pt supine with flexed knee has increased pain with
passive extension of the same leg

Brudzinskis
Supine pt with neck flexed will raise knees to take
pressure off of the meninges
Present in 50% of acute bacterial meningitis cases

Cranial Nerve Palsies

IV, VI, VII

Seizures

MENINGITIS
Clinical Manifestations - Meningococcemia
Prominent rash
Diffuse purpuric lesions principally involving the
extremities

Fever, hypotension, DIC

History of terminal complement deficiency
Classic findings often absent
Neonates
Elderly

MENINGOCOCCEMIA

MENINGOCOCCAL MENINGITIS

LOOK @ AGE/ARMY
RECRUITS/COLLEGE
STUDENTS/
Rash

MENINGITIS
Diagnosis
Assess for increased ICP
Papilledema
Focal neurologic findings

Defer LP until CT scan or MRI obtained if any of

above present
If suspect meningitis and awaiting neuroimaging
Obtain BCs and start empiric Abx

PAPILLEDEMA

Obtain CT scan before lumbar puncture in

patients with:
Immunucompromised state
History of CNS disease
New onset seizures
Papilledema
Altered level of consciousness
Focal neurologic signs

 Obtain blood cultures and give empiric

antibiotics if LP is delayed

Gram negative:
Diplococci: Meningococcus
Bacilli: E. coli
Coccobacilli: H influenzae
(small, pleomorphic)

Gram Positive:
Diplococci: Pneumococcus
Chains: Strep Group B
Clusters: Staph
Rods & cocobacilli: Listeria

LP-CSF

Tube # 1 Protein & Glucose

Tube # 2 Gram stain & Culture
Tube # 3 Cell count & differential
Tube # 4 Store ( PCR, viral studies etc)

MENINGITIS
Diagnosis
CSF Findings :
Opening pressure
Appearance
Cell count & differential
Glucose
Protein
Gram stain & culture

 Opening pressure: high, > 200 mmH20

Cloudy
1000-5000 cells/mm3 with a neutrophil
predominance of about 80-95%
<40mg/dl and less than 2/3 of the serum
glucose
Protein elevated

MENINGITIS
Diagnosis
Rapid Tests
CIE (Counter immunoelectrophoresis/ latex
agglut.)
PCR

CT/MRI
Little role in DIAGNOSIS of menigitis
Obtain if suspect increased ICP

MENINGITIS
Diagnosis
Additional Tests
CBC w/ diff
Blood cultures
CXR
Electrolytes and renal function

MENINGITIS
Differential Diagnosis
CNS infections (abscess, encephalitis)
Viral/ Tb/ Lyme meningitis
Ricketsial infections
Cerebral vasculitis
Subarachnoid hemorrhage
Neurosyphilis
NMO-SD

MENINGITIS
Treatment
Emergent empirical antimicrobial therapy
Based on age and underlying disease status

Empiric antibiotic regimines

Neonates (<3 months)
Ampicillin plus a third generation cephalosporin

Children
Third generation cephalosporin ( alternative -ampicillin and
chloramphenicol)

Young adults
Third generation cephalosporin (Ceftriaxone) + Vancomycin

MENINGITIS
Treatment
Empiric Antibiotic Regimines
Older adults
Ampicillin in combination with third generation
ceph.

Postneurosurgical Pts
Vancomycin plus ceftazidime until cultures are
available

MENINGITIS
Treatment
N. Meningitidis
High dose Pen G

S. pneumoniae
Ceftriaxone
For areas with high level resistance
Vancomycin plus third generation cephalosporin or
rifampin

MENINGITIS
Treatment
Gm (-) Enterics
Third generation cephalosporins

L. monocytogenes
Ampicillin

S. aureus
Vancomycin or Nafcillin

S. epidermidis
Vancomycin

MENINGITIS
Treatment
Duration of Treatment
Dependent on infecting organism
Average of 10-14 days
Gm (-) bacilli for 3 weeks

MENINGITIS
Treatment
Steroids
Shortly before or along with antibiotics. Do not
give steroids after antibiotic treatment.
de Gans J, van de Beek D. Dexamethasone in adults with
bacterial meningitis. N Engl J Med. 2002;347:1549-56.

ADJUNCTIVE DEXAMETHASONE
IN BACTERIAL MENINGITIS
Attenuates subarachnoid space inflammatory response resulting from
antimicrobial-induced lysis
Recommended for infants and children with Haemophilus influenzae
type b meningitis and considered for pneumococcal meningitis in
childhood, if commenced with or before parenteral antimicrobial
therapy
Clinical trials (predominantly in infants and children) have demonstrated
reduction in neurologic and/or audiologic sequelae
Recommended in adults with pneumococcal meningitis
Administer at 0.15 mg/kg every 6 hours for 2-4 days concomitant with or
just before first antimicrobial dose

MENINGITIS
Prognosis
Pneumococcal Meningitis
Associated with the highest mortality rate
20-30%

Permanent neurologic sequelae

1/3 of pts
Hearing loss
Mental retardation
Seizures
Cerebral Palsy

MENINGITIS
Vaccinations
Asplenic pts should have had a
pneumoccocal vaccine prior to their
splenectomy
Vaccines available for H. influenza
Prophylaxis for N. meningitidis contacts
Rifampin

MENINGITIS
COMMONLY ASKED QUESTIONS

WHAT ARE NORMAL CSF FINDINGS?

Protein
0.45 gm/L
Elevated with Diabetes
Elevated with neuropathies of any cause
Elevated with increasing age
Elevated by bleeding into the CSF (SAH or
traumatic)
0.01 gm/L for every 1000 RBCs

WHAT ARE NORMAL CSF FINDINGS?

Glucose
60 % of blood glucose
In persons with hyperglycemia it takes several hours
for CFS and blood glucose to equilibrate

Low CSF glucose

Bacterial infection
Tuberculosis, cryptococcosis, carcinomatous
SAH
Sarcoidosis
Occasional viral

WHAT ARE NORMAL CSF FINDINGS?

Cell count
<5 WBC (all mononuclear) and < 5 RBC considered
normal
Traumatic tap
WBC/RBC ratio = 1:1000

Pressure
<20
In patients with bacterial meningitis
wide range
40% >30, 10% < 14

CAN THE CSF RELIABLY DISTINGUISH BETWEEN A

BACTERIAL AND NON-BACTERIAL CAUSE OF
MENINGITIS?

Usually
Look at the whole pattern!

CAN THE CSF RELIABLY DISTINGUISH BETWEEN A

BACTERIAL AND NON-BACTERIAL CAUSE OF
MENINGITIS?
Glucose
<2.5 suggests bacterial
< 0.5 highly suggests bacterial

Protein
> 2.5 suggests bacterial

Cell count
>500 suggests bacterial
>1000 highly suggests bacterial

% polys
>50 suggests bacterial

ARE THERE EXCEPTIONS?

Early viral can have a predominance of polys
Some viral can have low CFS glucose
Listeria can have predominance of
mononuclear cells rather than polys
TB can have predominance of polys

HOW MUCH DOES PRIOR ADMINISTRATION OF

ANTIBIOTICS ALTER THE CSF FINDINGS?

Not Much

HOW MUCH DOES PRIOR ADMINISTRATION OF

ANTIBIOTICS ALTER THE CSF FINDINGS?

48-72 hours of prior intravenous antibiotic

treatment has little effect on glucose, protein
and cell count
It will rarely change the CSF from a bacterial to
an aseptic formula

Prior antibiotic treatment will likely make the

cultures negative.

WHAT IS THE TYPICAL CLINICAL PRESENTATION

OF BACTERIAL MENINGITIS?

History
Headache: 75-90%
Photophobia: uncommon

Examination
Fever: 95%
Stiff Neck: 85%
Altered mental status: 80%
All three: 40%
Any one of the three: 100%

HOW GOOD ARE KERNIG AND

BRUDZINSKI SIGNS?
Originally related to severe, advanced TB
meningitis (not bacterial)
Not studied in a prospective study until 2002
(N=297)*
Sensitivity 5%
Specificity 95%

*Thomas KE et al. Clin Infect Dis. 2002;35:46-52

HOW IMPORTANT IS THE SPEED OF INITIATING

ANTIBIOTICS IN BACTERIAL MENINGITIS?

It is important
But it is not the critical prognostic factor

HOW IMPORTANT IS THE SPEED OF INITIATING

ANTIBIOTICS IN BACTERIAL MENINGITIS?

The clinical outcome is primarily influenced by

the severity of the illness at the time
antibiotics are initiated
Severity based on
Altered mental status
Hypotension
Seizures

HOW IMPORTANT IS THE SPEED OF INITIATING

ANTIBIOTICS IN BACTERIAL MENINGITIS?
No factors
9% with adverse outcome

One factor
33% with adverse outcome

Two or three factors

56% with adverse outcome

Therefore, though treatment should be administered

ASAP, the impact of antibiotic delay is a function of
the severity of disease at the time that treatment is
initiated

STEROIDS OR NO STEROIDS?

Steroids
(today)

STEROIDS OR NO STEROIDS?
Reduces morbidity and mortality*
Give before or at the same time as the first
dose of antibiotics
Dose studied
Dexamethazone 10 mg Q6H x 4 days
*Only shown for pneumococcal meningitis in adults
and haemophilus meningitis in children

DO YOU NEED TO DO A CT SCAN BEFORE

AN LP?

Usually not
A CT scan should never delay therapy (obtain
blood cultures)

DO YOU NEED TO DO A CT SCAN BEFORE

AN LP?
Prospective studies*
N = 412
Predictors of CNS mass lesion
History
> 60 years old
Immunocompromised
Hx of prior CNS disease
Hx of seizure w/in 1 week prior to onset
Examination
Focal neurological findings
Altered mental status
Papilledema

*Gopal et al. Arch Intern Med. 1999;159:2681-5

Hasbun and Abrahams. N Engl J Med 2001:345:1727-33

HOW CONTAGIOUS IS MENINGITIS?

ARE WE AT RISK WHEN WE CARE FOR A PATIENT?

Not really
The only bacterial meningitis that is spread
from person to person is meningococcal
The risk is very low
Household contacts have about a 1% risk
Health care workers have not been shown to have a risk
After 24 hours of treatment this is no risk

WHAT IS ASEPTIC MENINGITIS?

It is a term used to mean non-pyogenic
bacterial meningitis
It describes a spinal fluid formula that typically
has:
A low number of WBC
A minimally elevated protein
A normal glucose

It has a much bigger differential diagnosis

than viral meningitis.

WHAT ARE THE

TREATABLE CAUSES OF ASEPTIC
MENINGITIS/ENCEPHALITIS SYNDROME?
Infectious
Non-Infectious

HSV 1 and 2
Syphilis
Listeria (occasionally)
Tuberculosis
Cryptococcus
Leptospirosis
Cerebral malaria
African tick typhus
Lyme disease

Carcinomatous
Sarcoidosis
Vasculitis
Dural venous sinus
thrombosis
Migraine
Drug
Co-trimoxazole
IVIG
NSAIDS

MENINGITIS
Conclusion
Meningitis is an infectious disease
emergency
Mortality is often high but can be prevented
with appropriate medical therapy
If you consider meningitis in your
differential, you are committed to an LP and
empiric antibiotics