Acute bacterial meningitis

Bacterial meningitis is an acute purulent infection within the subarachnoid

space.
Associated with CNS inflammatory reactions that may result in decreased
consciousness, seizure, raised intracranial pressure and stroke.
The meninge, subarachnoid space and the brain parenchyma are all
frequently involved in the inflammatory reaction meningoencephalitis.
Epidemiology

The bacterial meningitis is the most common form of suppurative CNS

infection
Currently, the organisms most commonly responsible for community
acquired bacterial meningitis are
● Streptococcus pneumoniae (∼50%),
● N. meningitidis (∼25%),
● group B streptococci (∼15%),
● Listeria monocytogenes (∼10%).
● H. influenzae now accounts for <10% of cases of bacterial meningitis
in most series.
ETIOLOGY

S. pneumoniae is the most common cause of meningitis in adults >20 years of

age, accounting for nearly half the reported cases.
There are a number of predisposing conditions that increase the risk of
pneumococcal meningitis, the
the most important of which is pneumococcal pneumonia.
Additional risk factors include coexisting acute or chronic pneumococcal
sinusitis or otitis media, alcoholism,diabetes, splenectomy,
hypogammaglobulinemia,
complement deficiency, and head trauma
• Mortality remains ∼20% despite antibiotic therapy.
• N. meningitidis accounts for 25% of all cases of bacterial meningitis (0.6
cases per 100,000 persons
per year) and for up to 60% of cases in children and
young adults between the ages of 2 and 20.

• The presence of petechial or purpuric skin lesions can provide an important

clue to the diagnosis of meningococcal infection.
• In some patients the disease is fulminant, progressing to death within hours
of symptom onset. Infection may be initiated by nasopharyngeal
colonization, which can result in either an asymptomatic carrier state or
invasive meningococcal disease.
• Enteric gram-negative bacilli are an increasingly common cause of
meningitis in individuals with chronic and debilitating diseases such as
diabetes, cirrhosis, or alcoholism and in those with chronic urinary tract
infections.
• Gram-negative meningitis can also complicate neurosurgical procedures,
particularly craniotomy.

• Group B streptococcus, or S. agalactiae, was previously responsible for

meningitis predominantly in neonates, but it has been reported with
increasing frequency in individuals >50 years of age, particularly those with
underlying diseases.

• L. monocytogenes has become an increasingly important cause of

meningitis in neonates (<1 month of age), pregnant women, individuals >60
years, and immunocompromised individuals of all ages.
• The frequency of H. influenzae type b meningitis in children has declined
dramatically since the introduction of the Hib conjugate vaccine, although
rare cases of Hib meningitis in vaccinated children have been reported. More
frequently, H. influenzae causes meningitis in unvaccinated children and
adults

• Staphylococcus aureus and coagulase- negative staphylococci are

important causes of meningitis that occurs after invasive neurosurgical
procedures, particularly shunting procedures for hydrocephalus, or as a
complication of the use of subcutaneous Ommaya reservoirs for
administration of intrathecal chemotherapy

PATHOPHYSIOLOGY•

• The most common bacteria that cause meningitis, S. pneumoniae and

N.meningitidis,initially colonize the nasopharynx by attaching to
nasopharyngeal epithelial cells.

• Bacteria are transported across epithelial cells in membrane bound vacuoles

to the intravascular space or invade the intravascular space by creating
separations in the apical tight junctions of columnar epithelial cells.

• Once in the bloodstream, bacteria are able to avoid phagocytosis by

neutrophils and classic complement–mediated bactericidal activity because
of the presence of a polysaccharide capsule.

• Bloodborne bacteria can reach the intraventricular choroid plexus, directly

infect choroid plexus epithelial cells, and gain access to the CSF.

• Bacteria are able to multiply rapidly within CSF because of the absence of
effective host immune defenses.
• Normal CSF contains few white blood cells (WBCs) and relatively small
amounts of complement proteins and immunoglobulins.

• A critical event in the pathogenesis of bacterial meningitis is the

inflammatory reaction induced by the invading bacteria.

• Many of the neurologic manifestations and complications of bacterial

meningitis result from the
immune response to the invading pathogen rather than
from direct bacteria-induced tissue injury.

• As a result, neurologic injury can progress even after the CSF has been
sterilized by antibiotic therapy.

• Much of the pathophysiology of bacterial meningitis

is a direct consequence of elevated levels of CSF cytokines and chemokines.

• TNF and IL-1 act synergistically to increase the permeability of the

blood-brain barrier, resulting in induction of vasogenic edema and the
leakage of serum proteins into the subarachnoid space.

• The subarachnoid exudate of proteinaceous material and leukocytes

obstructs the flow of CSF through the ventricular system and diminishes the
resorptive capacity of the arachnoid granulations in the dural sinuses,
leading to obstructive and communicating hydrocephalus and concomitant
interstitial edema.

During very early stages of meningitis :

● Increase in cerebral blood flow
Followed by a decrease in cerebral blood flow and loss of cerebrovascular
autoregulation.

Narrowing of the large arteries at the base of the brain due to encroachment
by the purulent exudate in the subarachnoid space and infiltration of the
arterial wall by inflammatory cells with intimal thickening vasculitis also
occur and may result in ischemia and infarction, obstruction of branches of
the middle cerebral artery by thrombosis, thrombosis of the
major cerebral venous sinuses, and thrombophlebitis of the cerebral cortical

• • The combination of interstitial, vasogenic, and cytotoxic edema leads to

raised ICP and coma.
• Cerebral herniation usually results from the effects of cerebral edema,
either focal or generalized;
hydrocephalus and dural sinus or cortical vein thrombosis may also play a
role.

CLINICAL PRESENTATION

● acute fulminant illness that progresses rapidly in a few hours

● subacute infection that progressively worsens over several days.
classic clinical triad of meningitis
fever, headache, and nuchal rigidity

A decreased level of consciousness occurs in >75% of patients and can vary

from lethargy to coma.

• Nausea, vomiting, and photophobia are also common complaints.

● Seizures 20-40% during course of illness
● Focal seizures due to focal arterial ischemia infractions
● Cortical venous thrombosis + hemorrhage
● Focal edema
● Generalized seizure activity and status epilepticus - hyponatremia or
cerebral anorexia
● Toxic effect of antimicrobial agents ( high dose penicillin)
● Increased ICP major cause of obtundation and coma.
● 90% patients will have a CSF opening pressure
Signs of increased ICP
● Reduced level of consciousness
● Papilledema
● Dilated poorly reactive pupils (sixth nerve palsies)
● Decerebrate posturing
● Cushing’s reflex { bradycardia, hypertension, irregular respiration }
● Cerebral herniation most disastrous complication 1%-8%
 Specific clinical features
● Rash of meningococcemia _ diffuse erythematous
maculopapular rash resembles viral exanthem, but
meningococcemia rapidly becomes petechial.
● Petechiae are found on the trunk and lower extremities, mucous
membranes and conjunctiva, and occasionally on the palms and
soles.
Diagnose

● Basic labs
● Blood culture
● CSF fluid analysis and gram stain
● Imaging { MRI preferred over CT scan }

Differential diagnose

● HSV encephalitis
● Rocky mountain spotted fever
● Brain abscess
● Subarachnoid hemorrhage
● Chemical meningitis due to rupture of tumor contents into CSF
● Drug induced
● Drug induced hypersensitivity meningitis
● Meningitis associated with inflammatory disorders such as sarcoid,
systemic lupus erythematosus and behcet’s syndrome
● Subacutely involved meningitis caused by
○ mycobacterium tuberculosis,
○ cryptococcus neoformans,
○ histoplasma capsulatum,
○ coccidioides immitis,
 ○ treponema pallidum.

Treatment

● EMPIRICAL ANTIMICROBIAL THERAPY

The goal is to begin antibiotic therapy within 60 min of the patient's arrival
in the emergency room before the result of CSF gram stain and culture is
known.

● S. pneumonia and N. meningitidis are the most common etiologic

organism of community acquired bacterial meningitis.
Due to the resistance of penicillin cephalosporins { S. pneumonia } the
empirical therapy of community acquired suspected bacterial meningitis in
children and adults should include a combination of :
❖ Dexamethasone
❖ Third generation of cephalosporin { ceftriaxone or cefotaxime }
❖ Vancomycin
❖ Cyclosporine as HSV encephalitis
❖ Doxycycline { tick season } to treat tick borne bacterial
Ceftriaxone or cafotoxamine provides good coverage for susceptible S.
pneumonia, group B streptococci, and H. influenza and adequate coverage
of N. meningitidis.
Ampicillin should be added to the empirical regimen to cover L.
monocytogenes in individuals <3 months and those with>55 years and those
with impaired immunity due to chronic illness, organ transplantation =,
pregnancy, malignancy, or immunosuppressive therapy .
Specific antimicrobial therapy
Meningococcal meningitis { N. meningitidis } : penicillin G remain the
antibiotic of choice caused by susceptible strains
CSF isolates of N. meningitidis should be tested for penicillin and
ampicillin susceptibility , if resistance is found, cefotaxime and
ceftriaxone should be substituted for penicillin.

● A 7 days course of IV antibiotics therapy is adequate for

uncomplicated meningococcal meningitis.
● The index case and all close contacts should receive
chemoprophylaxis with 2 day regimen of rifampin
● Rifampin contraindication in pregnancy
● alternative , adults can be treated with one dose of ciprofloxacin,
one dose of azithromycin or one intramuscular dose of
ceftriaxone.
Close contacts : individuals who have contact with oropharyngeal
secretions, either through kissing or by sharing toys, beverages or
cigarettes.

Pneumococcal meningitis : initiated with cephalosporin and

vancomycin.
If the MIC > 1 ug\mL of the cefotaxime or ceftriaxone, vancomycin is the
antibiotic of choice.
● A 2 weeks course of intravenous antimicrobial therapy is
recommended for pneumococcal meningitis.
Listeria meningitis: ampicillin for at least 3 weeks
● Gentamicin is often added as an adjustment for serum levels and
renal function.
● Penicillin allergic patients should take a combination of
trimethoprim and sulfamethoxazole.

Staphylococcal meningitis : treated with nafcillin

● Vancomycin is the drug of choice for methicillin resistant staph
and patients with penicillin allergy.

Gram negative bacillary meningitis : ceftriaxone cefotaxime

ceftazidime.
● P. aeruginosa : ceftazidime, cefepime or meropenem
A 3 weeks of IV antibiotic therapy for gram-bacilli

Adjunctive therapy

Bactericidal antibiotics lead to production of inflammatory cytokines

IL-1 and TNF in subarachnoid space, dexamethasone inhibits the
synthesis of cytokines at the level of mRNA, decreasing CSF outflow
resistance and stabilizing the blood brain barrier.
Dexamethasone should be given 20 min before antibiotic therapy
otherwise its not useful if its given after antibiotics
Dexamethasone decreases meningeal inflammation and neurological
sequelae such as sensorineural hearing loss in children predominantly
with meningitis due to H. influenza and S. pneumonia.
INCREASED INTRACRANIAL PRESSURE :
EMERGENCY TREATMENT: elevation of the patient’s head to 30
degree-45 degree, intubation and hyperventilation { PaCO2- 30mmHg}
and mannitol.
● Should be managed in ICU
● Accurate ICP measurement for ICP monitoring device

PROGNOSIS

Mortality :
● H. influenza, N. meningitidis or group B streptococci : 3-7%
● L. monocytogenes : 15%
● S. pneumonia : 20%
Risk of death in bacterial meningitis increasing with :
● Decreased level on consciousness on admission
● Onset of seizure within 24hr of admission
● Signs of ICP increased
● Infancy and age >50 years
● Comorbid conditions including : shock and need for mechanical
ventilation
Moderate to severe sequelae occur in 25% of survivor
Common sequelae including :
● Decreased intellectual function
● Memory impairment seizures
● Hearing loss
● Dizziness
● Gait disturbance