ACUTE BACTERIAL • meninges

• subarachnoid space
MENINGITIS • brain parenchyma

ACUTE BACTERIAL MENINGITIS

Bacterial meningitis
• is an acute purulent infection
within the subarachnoid space.
• associated with a CNS
inflammatory reaction
• decreased consciousness
• seizures
• raised intracranial pressure
(ICP)
• stroke

Meningoencephalitis:
EPIDEMIOLOGY • 60% of cases in children and young
• Bacterial meningitis is the most adults between the ages of 2 and
common form of suppurative 20.
CNS infection • Pathognomonic: the presence of
• a dramatic decline in the incidence petechial or purpuric skin lesions
of meningitis due to Haemophilus • the disease is fulminant,
in.uenzae, and a smaller decline in progressing to death within hours
that due to Neisseria meningitidis, of symptom onset.
following the introduction and • initiated by nasopharyngeal
increasingly widespread use of colonization
vaccines for both these organisms • asymptomatic carrier state
• organisms most commonly • invasive meningococcal
responsible for community- disease.
acquired bacterial meningitis: • Individuals with deficiencies of any
• Streptococcus pneumoniae of the complement components,
(50%) including properdin, are highly
• N. meningitidis (25%) susceptible to meningococcal
infections.
• group B streptococci (15%)
• Listeria monocytogenes (10%) Enteric gram-negative bacilli
H. infuenzae (10%) • increasingly common cause of
meningitis in individuals with
ETIOLOGY chronic and debilitating diseases
S. pneumoniae • Gram-negative meningitis can also
• is the most common cause of complicate neurosurgical
meningitis in adults procedures, particularly
• 20 years of age craniotomy.
• nearly half the reported
cases Group B streptococcus, or S.
agalactiae
• Predisposing conditions that • previously responsible for
increase the risk of pneumococcal meningitis predominantly in
meningitis: neonates
• pneumococcal pneumonia • increasing frequency in individuals
• coexisting acute or chronic 50 years of age, particularly those
pneumococcal with underlying diseases.
• sinusitis or otitis media
• alcoholism L. monocytogenes
• diabetes • increasingly important cause of
meningitis in neonates (1 month of
• splenectomy
age)
• hypogammaglobulinemia,
• pregnant women
• complement de.ciency
• individuals 60 years and
• head trauma with basilar skull
immunocompromised individuals of
fracture and CSF rhinorrhea. all ages
• Mortality remains 20% despite
antibiotic therapy.
• Infection is acquired by ingesting
foods contaminated by Listeria:
contaminated coleslaw, milk, soft cheeses,
N. meningitidis and several types of “ready-to-eat” foods
• 25% of all cases of bacterial including delicatessen meat and uncooked
meningitis hotdogs.

H. influenzae type b
• Meningitis in children has declined • Normal CSF contains few
dramatically since the introduction white blood cells (WBCs)
of the Hib conjugate vaccine • small amounts of
• causes meningitis in unvaccinated complement proteins and
children and adults immunoglobulins.
2. Phagocytosis of bacteria is further
Staphylococcus aureus and impaired by the fluid nature of CSF
coagulase-negative
staphylococci → critical event: INFLAMMATORY
• important causes of meningitis that REACTION induced by the invading
follows Invasive neurosurgical bacteria
procedures
• shunting procedures for 1. Lysis of bacteria with the
hydrocephalus subsequent
• complication of the use of release of cell-wall (LPS, techoic &
subcutaneous Ommaya peptidoglycan) components into the
reservoirs for administration of subarachnoid space
intrathecal chemotherapy. - induce meningeal in.ammation by
stimulating the production of
PATHOPHYSIOLOGY in.ammatory cytokines and
chemokines by microglia,
• The most common bacteria that astrocytes, monocytes,
cause meningitis, S. pneumoniae microvascular endothelial cells, and
and N.meningitidis, CSF leukocytes
colonize the nasopharynx → attach to 2. Formation of a purulent exudate in
nasopharyngeal epithelial cells→ the subarachnoid space
transported across epithelial cells - cytokines including tumor necrosis
(membrane-bound vacuoles) → factor (TNF) and interleukin (IL) 1
intravascular space or invade the → increase in CSF protein
intravascular concentration and leukocytosis
space by creating separations in the
apical tight bacteremia and the inflammatory
junctions of columnar epithelial cells → cytokines
bloodstream → bacteria avoid → excitatory amino acids, reactive
phagocytosis by neutrophils and oxygen and nitrogen species (free
classic complement–mediated oxygen radicals, nitric oxide, and
bactericidal activity because of the peroxynitrite) → induce death of brain
presence of a polysaccharide cells
capsule → reach the intraventricular
choroid plexus → directly infect choroid • Much of the pathophysiology of
plexus epithelial cells → gain access to bacterial
the CSF meningitis is a direct consequence of
elevated
*S. pneumoniae, - can adhere to levels of CSF cytokines and
cerebral capillary endothelial cells and chemokines
subsequently migrate TNF & IL-1 act synergistically to
through or between these cells to increase the permeability of the blood-
reach the brain barrier→ vasogenic edema and
CSF the leakage of serum proteins into the
→ Bacteria are able to multiply rapidly subarachnoid space → obstructs flow
within CSF. Reasons: of CSF through the ventricular system
1. Prevention of the effective and diminishes the resorptive capacity
opsonization of bacteria of the arachnoid granulations in the
dural sinuses → obstructive and
communicating hydrocephalus → • Subacute infection - progressively
interstitial edema worsens over several days
• The classic clinical triad of
Inflammatory cytokines upregulate the
meningitis (90% of cases)
expression of selectins on cerebral
capillary endothelial cells and • Fever
leukocytes→ leukocyte adherence to • Headache
vascular endothelial cells → migration • nuchal rigidity (“stiff neck”)
into the CSF.

The adherence of leukocytes to • Alteration in mental status

capillary endothelial cells increases the (75% of cases)
permeability of blood vessels → • Nausea, vomiting, and
leakage of plasma proteins into the photophobia
CSF→ infammatory exudate. • Seizures
Neutrophil degranulation → release of
toxic metabolites → cytotoxic edema, Focal seizures
cell injury, and death. • due to focal arterial ischemia or
infarction
During the very early stages of • cortical venous thrombosis with
meningitis there is hemorrhage
an increase in cerebral blood flow then • focal edema
decrease in cerebral blood flow and a
loss of cerebrovascular autoregulation Generalized seizure activity and status
epilepticus
encroachment by the purulent exudate • hyponatremia
in the subarachnoid space and • cerebral anoxia
infiltration of the arterial wall by • the toxic effects of antimicrobial
inflammatory cells with intimal agents such as high-dose penicillin.
thickening (vasculitis)→ narrowing of
the large arteries at the base of the Obtundation and coma
brain → ischemia and infarction, • raised ICP
obstruction of branches of the middle • 90% will have a CSF opening
cerebral artery by thrombosis, pressure = 180 mmH2O
thrombosis of the major cerebral
• 20% have opening pressures = 400
venous sinuses, and thrombophlebitis
mmH2O.
of
the cerebral cortical veins. • Signs of increased ICP
• reduced level of consciousness
The combination of interstitial, • papilledema
vasogenic, • dilated poorly reactive pupils
and cytotoxic edema leads to raised • sixth nerve palsies
ICP and coma. • decerebrate posturing
• Cushing refex (bradycardia,
Cerebral herniation hypertension, and irregular
- effects of cerebral edema, either respirations)
focal or generalized • *cerebral herniation – the most
- hydrocephalus and dural sinus or disastrous complication
cortical vein thrombosis
Some notable specific clinical features:
CLINICAL PRESENTATION • rash of meningococcemia
• Acute fulminant illness - that
progresses rapidly in a few hours
• begins as a diffuse
erythematous maculopapular
rash
• rapidly become petechial.
• Petechiae are found on the
trunk and lower extremities, in
the mucous membranes and
conjunctiva, and occasionally
on the palms and soles
DIAGNOSIS therefore, administration of 50 mL
• Blood cultures of 50% glucose (D50) prior to LP,
• examination of the CSF as commonly occurs in emergency
room settings, is unlikely to alter
• the need to obtain CSF glucose concentration
neuroimaging studies (CT or
MRI) prior to LP requires clinical
• The latex agglutination (LA) test -
judgment
rapid diagnosis of bacterial
meningitis, especially in patients
Considerations:
pretreated with antibiotics and in
In an immunocompetent patient (-)
whom CSF Gram’s stain and culture
history of recent head trauma, a
are negative.
normal level of consciousness, and no
evidence of papilledema or focal - specificity of 95 to 100% for S.
neurologic deficits pneumoniae and N. meningitides
= SAFE TO PERFORM LP - the sensitivity = 70 to 100% for
detection of S. pneumoniae and 33
If LP is delayed in order to obtain to 70% for detection of N.
neuroimaging meningitidis antigens
studies, empirical antibiotic therapy
should be initiated after blood cultures • Limulus amebocyte lysate assay –
are obtained. Antibiotic therapy rapid diagnostic test for the
initiated a few hours prior to LP detection of gram-negative
will not significantly alter the CSF endotoxin in CSF
WBC count or glucose - specificity of 85 to 100%
concentration, nor is it likely to
and a sensitivity
prevent visualization of organisms approaching 100%
by Gram’s stain.
• CSF polymerase chain reaction
(PCR) tests
- not as useful in the
diagnosis of bacterial
meningitis
- for detecting DNA from
bacteria in CSF

• NEUROIMAGING:
- MRI is preferred over CT because of
its superiority in demonstrating
areas of cerebral edema and
ischemia

• Petechial skin lesions, should be

biopsied.
• Use of the CSF/serum glucose ratio o The rash of meningococcemia
corrects for hyperglycemia that results from the dermal seeding
may mask a relative decrease in of organisms with vascular
the CSF glucose concentration. endothelial damage

DIFFERENTIAL DIAGNOSIS
• It takes from 30 min to several 1. Viral meningoencephalitis
hours for CSF glucose
concentration to reach equilibrium
with blood glucose concentrations;
 o (HSV) encephalitis, can mimic 5. chemical meningitis - due to
the clinical presentationof rupture of tumor contents into the
bacterial meningitis CSF (e.g., from a cystic glioma,
i. headache, fever, altered craniopharyngioma epidermoid or
consciousness, dermoid cyst)
focal neurologic deficits (e.g., 6. drug-induced hypersensitivity
dysphasia, hemiparesis), and focal or meningitis
generalized seizures. 7. carcinomatous or lymphomatous
meningitis
HSV Encephalitis Bacterial
Meningitis
8. meningitis associated with
inflammatory disorders such as
CSF: a PMN pleocytosis
sarcoid, systemic lupus
lymphocytic and
erythematosus (SLE), and Behchet
pleocytosis with a hypoglycorrhachia
disease; pituitary apoplexy;
normal glucose
concentration 9. uveomeningitic syndromes (Vogt-
MRI: parenchymal No MRI Koyanagi -Harada syndrome)
changes, abnormalities 10. Subacutely evolving meningitis
especially in o Mycobacterium tuberculosis
orbitofrontal o Cryptococcus neoformans
and medial o Histoplasma capsulatum
temporal lobes o Coccidioides immitis
o Treponema pallidum
2. Rocky Mountain spotted fever
(RMSF) Empirical Antimicrobial Therapy
o transmitted by a tick bite (Table 360-2)
o Rickettsia rickettsii. • Goal: antibiotic therapy within 60
o high fever, prostration, myalgia, min of a patient’s arrival in the
headache, and emergency room
o nausea and vomiting • Started before the results of CSF
o characteristic rash within 96 h of Gram’s stain and culture are
the onset of symptoms. known.
o Diffuse erythematous • S. pneumoniae and N. meningitidis
maculopapular rash → - most common etiologic organisms
progresses to a petechial rash of community-acquired bacterial
→ to a purpuric rash →, meningitis
(untreated) skin necrosis or • S. pneumoniae - children and
gangrene adults
o begins in the wrist and ankles, o third-generation
and then spreads distally and cephalosporin (e.g.,
proximally within a matter of a ceftriaxone or cefotaxime)
few hours and involves the and vancomycin.
palms and soles. \ • Ceftriaxone or cefotaxime
o Dx: immunofluorescent staining o S. pneumoniae
of skin biopsy specimens. o group B streptococci
o H. in.uenzae
3. Focal suppurative CNS infections o N. meningitidis.
including subdural and epidural • Cefepime
empyema and brain abscess,
o Equal to cefotaxime or
o MRI should be performed
ceftriaxone against S.
promptly
pneumoniae and N.
meningitidis
4. Subarachnoid hemorrhage
 o greater activity against • chemoprophylaxis with a 2-day
Enterobacter spp. and regimen of rifampin (600 mg
Pseudomonas aeruginosa. every 12 h for 2 days in adults
• cefepime = cefotaxime and 10 mg/kg every 12 h for 2
o in the treatment of days in children 1 year).
penicillin-sensitive • Alternatively, adults can be
pneumococcal and treated with one dose of
meningococcal meningitis ciprofloxacin (750 mg), one
• Ampicillin should be added to the dose of azithromycin (500 mg),
empirical regimen - L. or one intramuscular dose of
monocytogenes ceftriaxone (250 mg)
o 3 months of age
o Age 55 PNEUMOCOCCAL MENINGITIS
o those with suspected • initiated with a cephalosporin
impaired cell-mediated (ceftriaxone, cefotaxime or
immunity cefepime) and vancomycin.
• Vancomycin + Ceftazidime • Should be tested for sensitivity
o Hospital-acquired meningitis to penicillin and the
o meningitis following cephalosporins.
neurosurgical procedures • For S. pneumoniae meningitis,
o staphylococci and gram- an isolate of S. pneumoniae
negative organisms susceptible to penicillin with a
including P. aeruginosa minimal inhibitory
o Ceftazidime should be concentration (MIC) <0.06
substituted for ceftriaxone ug/mL, to have intermediate
or cefotaxime in resistance when the MIC is 0.1
neurosurgical patients and to 1.0 ug/mL, and to be highly
in neutropenic patients. resistant when the MIC>1.0
• Meropenem ug/mL.
o carbapenem antibiotic that • For meningitis due to pneumococci
is highly active against L. with cefotaxime or ceftriaxone
monocytogenes • MICs ≥ 0.5 ug/mL = treatment with
o effective P. aeruginosa cefotaxime or ceftriaxone is usually
meningitis adequate
o penicillin-resistant • MIC > 1 ug/mL = vancomycin is the
pneumococci antibiotic of choice.

Specific Antimicrobial Therapy

• Rifampin + vancomycin for its
synergistic effect but is inadequate
MENINGOCOCCAL MENINGITIS as monotherapy
• Patients with S. pneumoniae
N. meningitidis meningitis = repeat LP performed
• ceftriaxone and cefotaxime 24 to 36 h after the initiation of
provide adequate empirical antimicrobial therapy to document
coverage sterilization of the CSF. Failure to
• penicillin G - antibiotic of choice sterilize the CSF after 24
for meningococcal meningitis • to 36 h = resistance!
caused by susceptible strains. • Patients with penicillin- and
• A 7-day course of intravenous cephalosporin-
antibiotic therapy is adequate • resistant strains of S. pneumoniae
for uncomplicated who do not respond to IV
meningococcal meningitis. vancomycin alone may benefit
 from the addition of Adjunctive Therapy
intraventricular vancomycin. • Dexamethasone
• A 2-week course of intravenous o inhibiting the synthesis of
antimicrobial therapy is IL-1 and TNF at the level of
recommended for pneumococcal mRNA, decreasing CSF
meningitis. outflow resistance, and
stabilizing the blood-brain
L. MONOCYTOGENES MENINGITIS barrier
• Ampicillin for at least 3 weeks o given 20 min before
• Gentamicin is added (2 mg/kg antibiotic therapy inhibiting
loading dose, then 5.1 mg/kg per the production of TNF by
day given every 8 h and adjusted macrophages and microglia
for serum levels and renal only if it is administered
function). before these cells are
• trimethoprim [10 to 20 (mg/kg)/d] activated by endotoxin.
o does not alter TNF
+ sulfamethoxazole [50 to 100
(mg/kg)/d] given every 6 h = for production once it has been
penicillinallergic. induced.
o Decrease meningeal
STAPHYLOCOCCAL MENINGITIS in.ammation and neurologic
sequelae such as the
• Nafcillin - meningitis due to incidence of sensorineural
susceptible strains of S. hearing loss.
• aureus or coagulase-negative o may decrease the
staphylococci penetration of vancomycin
• Vancomycin is the drug of choice into CSF, and it delays the
for methicillin-resistant sterilization of CSF in
staphylococci and for patients experimental models of S.
allergic to penicillin. pneumoniae meningitis.
• CSF should be monitored during
Increased Intracranial Pressure
therapy. If the CSF is not sterilized
after 48 h of intravenous • elevation of the patient’s head to
vancomycin therapy, add either 30 to 45O
intrathecal or intraventricular • intubation and hyperventilation
vancomycin, 20 mg once daily (PaCO 25 to 30 mmHg),
• mannitol
GRAM-NEGATIVE BACILLARY
MENINGITIS • Patients with 2 increased ICP
should be managed in an intensive
• Third-generation cephalosporins: care unit
cefotaxime, ceftriaxone, and
ceftazidime EXCEPT: of meningitis PROGNOSIS
due to P. aeruginosa = ceftazidime.
• A 3-week course of intravenous
• Mortality is 3 to 7% for meningitis
antibiotic caused by H. influenzae, N.
meningitidis, or group B
streptococci;
• 15% for that due to L.
monocytogenes;
• 20% for S. pneumoniae.
• risk of death from bacterial
meningitis increases with
1. decreased level of consciousness
on admission
 2. onset of seizures within 24 h of - normal glucose (may be
admission decreased in mumps and
3. signs of increased ICP LCMV)
4. young age (infancy) and age
- normal to mildly elevated
>50
5. the presence of comorbid opening pressure
conditions including shock and/or - organisms are not seen on
the need for mechanical ventilation Gram’s stain or AF stained
6. delay in the initiation of smears or India ink
treatment. preparations
• Common sequelae: - PMNs may predominated in
o decreased intellectual function the first 48 hrs.
o memory impairment - As a rule, lymphocytic
o seizures pleocytosis with low glucose
o hearing loss and dizziness suggest fungal, listerial, or
o gait disturbances. TB meningitis or
noninfectious disorders
(2) PCR of viral nucleic acid
~ MARK TURINGAN - procedure of choice for HSV
ACUTE VIRAL MENINGITIS meningitis
- more sensitive than viral
Clinical Manifestations cultures
- fever, headache, and meningeal - used routinely to diagnose
irritation CMV, EBV, VZV
- headache usually frontal or (3) CSF culture
retroorbital with photophobia - 2 mL of CSF, refrigerated
and pain on moving the eyes and processed ASAP
- with malaise, myalgia, anorexia, - never stored in ~200C, virus
nausea and vomiting, unstable at this temp.
abdominal pain and/or diarrhea - should be in a ~700C freezer
- mild degree of lethargy and if stored for >20 hrs.
drowsiness (4) Other sources of viral isolation
- seizures or other focal - throat, stool, blood, urine
neurologic signs or symptoms - enterovirus in stool is not
indicates of involvement of diagnostic
brain parenchyma (5) Serologic studies
- useful for arboviruses
Epidemiology - less useful for HSV, VZV,
- some viruses have seasonal CMV, EBV
predilections: increased - diagnosis of acute viral
incidence during summer and infection can be made by
early fall documenting seroconversion
between acute-phase and
Laboratory Diagnosis convalescent sera or by
demonstrating the presence
(1) CSF examination of virus-specific IgM
- most important lab test antibodies
- lymphocytic pleocytosis (25- - IgM Abs persist for only a
500 cells/μL) few months after acute
- normal to slightly elevated infection except WNV IgM
protein (20-80 mg/dL)
 - useful mainly for in a certain geographic
retrospective establishment region
of a specific diagnosis - history of tick exposure
- the finding of oligoclonal sought in cases of Colorado
bands in electrophoresis tick fever or Powassan virus
may be suggestive of certain infection
viruses (3) HSV-2
(6) Other lab studies - probably the second most
- CBC, liver function tests, common viral cause of
ESR, BUN, plasma levels of meningitis
electrolytes, glucose, - cultures are invariably
creatinine, creatine kinase, negative
aldolase, amylase, and lipase - diagnosis made by CSF PCR
- genital lesions may not be
Differential Diagnosis present
(4) VZV
(1) bacterial meningitis - suspected in the presence of
(2) parameningeal infections or concurrent chicken pox or
partially treated bacterial shingles
meningitis - 40% occur in the absence of
(3) nonviral infections meningitides rash
with culture negative (fungal, - Can also produce cerebellar
tuberculous, parasitic, syphillis) ataxia
(4) neoplastic meningitis - CSF PCR used in the
(5) meningitis secondary to diagnosis
noninfectious inflammatory (5) EBV
diseases - may occur with or without
evidence of infectious
Specific Viral Etiologies mononucleosis syndrome
- diagnosis suggested by
(1) Enterovirus atypical lymphocytes in the
- most common cause of viral CSF or in the peripheral
meningitis blood
- typical case occurs in the - diagnose by SF PCR
summer months, esp. in - patient with CNS lymphoma
children < 15 y/o may be positive in PCR in the
- PE includes exanthemata, absence of
hand-foot-mouth disease, meningoencephalitis
herpangina, pleurodynia, (6) HIV
myopericarditis, - presence of HIV genome by
hemorrhagic conjunctivitis PCR or p24 protein
- diagnosis by PCR establishes the diagnosis
amplification of enteroviral - cranial nerve palsies
RNA from CSF common
(2) Arbovirus (7) Mumps
- typically occur in the - typically occurs in late winter
summer or early spring, esp. in males
- WNV suspected when cluster - orchitis, oophoritis, parotitis,
of meningitis cases are pancreatitis, or elevations in
preceded by death of birds serum lipase and amylase
 are suggestive but can be ~ Mary Ann Sunga
found with other viruses
- infection confers lifelong
immunity
- diagnosis made by isolation
from CSF and/or
demonstration of
seroconversion
(8) LCMV
- typically occurs late fall or
winter in individuals with
history of exposure to
rodents or their excreta
- with rash, pulmonary
infiltrates, alopecia, parotitis,
orchitis, or myopericarditis
- leucopenia,
thrombocytopenia, abnormal
liver function tests

Treatment
- in the usual case, treatment is
symptomatic and hospitalization
is not required
- patient left undisturbed in a
quiet, darkened room
- analgesics and antipyretics
- monitor fluid and electrolyte
status because hyponatremia
and SIADH may develop
- oral or IV acyclovir for HSV, VZV
and EBV
- highly active retroviral therapy
for HIV meningitis
- for patient with known deficient
humoral immunity, give IM or
IV IgG
- pleconaril for enteroviral
infections
- vaccination (Varivax) for VZV,
booster may be required to
maintain immunity

Prognosis
- most of the times, there’s full
recovery
- outcome in < 1 y/o: intellectual
impairment, learning
disabilities, hearing loss