Acute Bacterial Meningitis Beyond the Neonatal Period

Cause of bacterial meningitis and its treatment during the neonatal period (0-28 days)

are generally different from those in older infants and children

ETIOLOGY.

Organism -

First 2 mo of life - maternal flora or the environment of the infant - group B

Streptococcus, gram-negative enteric bacilli, and Listeria monocytogenes, H. influenzae

Bacterial meningitis in children 2 mo-12 yr of age is due to S. pneumoniae, N.

meningitidis, or H. influenzae type b.

Anatomic defects or immune deficits increase the risk of meningitis from less common

pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-

negative staphylococci, Salmonella spp, and L. monocytogenes.

EPIDEMIOLOGY.

- lack of immunity to specific pathogens

-- close contact (e.g., household, daycare centers, schools, military barracks) with

individuals having invasive disease,

-crowding, poverty,

-absence of breast-feeding for infants 2-5 mo of age.

The mode of transmission - person to person contact through respiratory tract secretions

or droplets. -

-host defense defects due to altered immunoglobulin production in response to

encapsulated pathogens may be responsible for the increased risk of bacterial meningitis

-defects of the complement system is associated with recurrent meningococcal infection,

-defects of the properdin system - risk of lethal meningococcal disease.

-Splenic dysfunction (sickle cell anemia) or asplenia (due to trauma, congenital defect,

staging of Hodgkin disease) -risk of pneumococcal, H. influenzae type b , meningococcal

sepsis and meningitis.

-T-lymphocyte defects (congenital or acquired by chemotherapy, AIDS, or malignancy) -

risk of L. monocytogenes infections of the CNS.

-Congenital or acquired CSF leak -cribriform plate and middle ear ,inner ear fistulas, CSF

leakage through a rupture of the meninges due to a basal skull fracture into the

cribriform plate or paranasal sinus- risk of pneumococcal meningitis.

-Lumbosacral dermal sinus and meningomyelocele - staphylococcal and gram-negative

enteric bacterial meningitis.

-Penetrating cranial trauma and CSF shunt

PATHOLOGY.

1. A meningeal exudate is distributed around the cerebral veins, venous sinuses,

convexity of the brain, and cerebellum and in the sulci, sylvian fissures, basal cisterns,

and spinal cord.

2. Ventriculitis

3. subdural effusions

4.. Perivascular inflammatory infiltrates

5. thrombosis of small cortical veins, occlusion of major venous sinuses, necrotizing

arteritis producing subarachnoid hemorrhage,

6. Cerebral infarction due to vascular occlusion from inflammation, vasospasm, and

thrombosis.

7. Inflammation of spinal nerves and roots produces meningeal signs,

8. inflammation of the cranial nerves produces cranial neuropathies of optic, oculomotor,

facial, and auditory nerves.

9. Increased intracranial pressure (ICP) - produces oculomotor nerve palsy due to the

presence of temporal lobe compression of the nerve during tentorial herniation. 10.

Abducens nerve palsy may be a nonlocalizing sign of raised ICP.

Increased ICP

  - cell death (cytotoxic cerebral edema),

   - cytokine-induced increased capillary vascular permeability (vasogenic

cerebral edema),

    - increased hydrostatic pressure

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may produce

excessive water retention, increasing ICP.

Raised CSF protein levels = increased vascular permeability of the blood-brain barrier

and the loss of albumin-rich fluid from the capillaries

Hypoglycorrhachia (reduced CSF glucose levels) = due to decreased glucose transport

by the cerebral tissue.

Damage to the cerebral cortex -infarction, necrosis, lactic acidosis, hypoxia, bacterial

invasion (cerebritis), toxic encephalopathy (bacterial toxins), raised ICP, ventriculitis,

and transudation (subdural effusions).

These pathologic factors result in the clinical manifestations of impaired consciousness,

seizures, hydrocephalus, cranial nerve deficits, motor and sensory deficits, and later

psychomotor retardation.

PATHOGENESIS.

Mechanism of infection

(1) direct invasion from - suppurative focus in the middle ear or mastoid spreads

through the dura and extends to the pia-arachnoid, causing generalized meningitis;

(2) suppuration inside cranium - such as a subdural abscess, brain abscess, or lateral

sinus thrombophlebitis, which causes the meninges to become inflamed,

(3) hematogenous spread - from an infectious focus in the upper respiratory tract

hematogenous dissemination of microorganisms from a distant site of infection;

bacteremia usually precedes meningitis.

Bacterial colonization of the nasopharynx is the source of the bacteremia.

viral upper respiratory tract infection may enhance the pathogenicity of bacteria

Bacterial capsules interferes with opsonic phagocytosis

Splenic dysfunction also reduces opsonic phagocytosis

Bacteria gain entry to the CSF through the choroid plexus of the lateral ventricles and

the meninges and then circulate to the extra cerebral CSF and subarachnoid space.

Bacteria rapidly multiplies in the CSF

The inflammatory response - neutrophilic infiltration, increased vascular permeability,

alterations of the blood-brain barrier, and vascular thrombosis.

cytokine-induced inflammation continues after the CSF has been sterilized

It causes the chronic inflammatory sequelae of pyogenic meningitis.

CLINICAL MANIFESTATIONS.

Two patterns. 1. Sudden onset with rapidly progressive manifestations of shock,

purpura, disseminated intravascular coagulation (DIC) and death within 24 hr.

2. Meningitis is preceded by upper respiratory tract or gastrointestinal symptoms,

followed by nonspecific signs of CNS infection such as increasing lethargy and irritability.

General symptoms & signs

fever

anorexia

poor feeding,

symptoms of upper respiratory tract infection,

myalgias, arthralgias,

tachycardia,

hypotension,

cutaneous signs- petechiae, purpura, erythematous macular rash.

Meningeal irritation - nuchal rigidity, back pain, Kernig sign (flexion of the hip 90

degrees with subsequent pain with extension of the leg), and Brudzinski sign

(involuntary flexion of the knees and hips after passive flexion of the neck while supine).

younger than 12-18 mo, Kernig and Brudzinski signs may not be evident

Increased ICP -

headache,

emesis,

bulging fontanel or widening of the sutures,

oculomotor or abducens nerve paralysis,

hypertension with bradycardia,

apnea or hyperventilation,

decorticate or decerebrate posturing,

stupor, coma, or signs of herniation.

Papilledema suggest a more chronic process, such as the presence of an intracranial

abscess, subdural empyema, or occlusion of a dural venous sinus.

Focal neurologic signs usually are due to vascular occlusion.

Cranial neuropathies of the ocular, oculomotor, abducens, facial, and auditory nerves

Seizures - due to cerebritis, infarction, or electrolyte disturbances

Seizures that occur on presentation or within the first 4 days of onset are of no

prognostic significance.

Seizures that persist after the 4th day of illness and those that are difficult to treat are

associated with a poor prognosis.

Alterations of mental status - = irritability, lethargy, stupor, coma.

due to increased ICP, cerebritis, or hypotension

Comatose patients - poor prognosis.

DIAGNOSIS.

Do LP -get CSF -

-neutrophilic pleocytosis,

-elevated protein

-reduced glucose concentrations

-identify microorganisms on Gram stain and culture

-latex particle agglutination. - Antigen is most consistently detected in the CSF

- Blood culture

LP should be performed when bacterial meningitis is suspected.

Contraindications for an immediate LP include

(1) evidence of increased ICP (other than a bulging fontanel),

(2) severe cardiopulmonary compromise

(3) infection of the skin overlying the site of the LP.

Thrombocytopenia is a relative contraindication for immediate LP.

If an LP is delayed, immediate empirical therapy should be initiated.

CT scanning for evidence of a brain abscess or increased ICP also should not delay

therapy.

LP may be performed after increased ICP has been treated or a brain abscess has been

excluded.

LP is usually performed with a patient in the flexed lateral position

needle is passed into the L3-L4 or L4-L5 intervertebral space.

Turbid CSF is present when the CSF leukocyte count exceeds 200-400/cu mm. Normal

healthy neonates may have as many as 30 leukocytes/cu mm, and older children

without viral or bacterial meningitis may have 5 leukocytes/mm3 in the CSF; in both age

groups, there is a predominance of lymphocytes or monocytes.

-pleocytosis may be absent in patients with severe overwhelming sepsis and meningitis

and is a poor prognostic sign.

-Pleocytosis with lymphocyte predominance can occur in early stage of acute bacterial

meningitis;

- neutrophilic pleocytosis may be present in patients during the early stages of acute

viral meningitis.

Gram stain is positive in most (70-90%) patients with bacterial meningitis.

Traumatic LP makes diagnosis of meningitis difficult. Repeat LP at another interspace

may produce less hemorrhagic fluid, but this fluid usually also contains red blood cells.

In traumatic LP gram stain, culture, and glucose level can help in diagnosis

Do C&S of CSF in such cases

Differential Diagnosis.

Organisms causing Meningitis

S. pneumoniae

N. meningitidis

H. influenzae type b

Mycobacterium tuberculosis

Nocardia

Treponema pallidum (syphilis)

Borrelia burgdorferi (Lyme disease)

ungi, - Coccidioides, Histoplasma, and Blastomyces

infections in compromised hosts - Candida, Cryptococcus, and Aspergillus

parasites- Toxoplasma gondii , cysticercosis, resulting from infection with the larval

stages ( Cysticercus cellulosae) of the pork tapeworm Taenia solium;

viruses.

Meningeal irritation seen in - Focal infections of the CNS including brain abscess and

parameningeal abscess (subdural empyema, cranial and spinal epidural abscess) Upper

lobe consolidation

Non infectious cause of meningeal irritation -malignancy,

collagen vascular syndromes, and

exposure to toxins.

examination of the CSF with

specific stains (Kinyoun carbol fuchsin for mycobacteria, India ink for fungi), cytology,

antigen detection (bacteria, Cryptococcus),

serology (syphilis),

viral culture (enterovirus).

CT or MRI of the brain,

blood cultures,

serologic tests

brain biopsy.

TREATMENT.

Antibiotics started after LP is performed.

If there are signs of increased ICP or focal neurologic findings, antibiotics should be

given without performing an LP and before obtaining a CT scan.

Treatment of increased ICP.

treatment of associated multiple organ system failure, such as shock and adult

respiratory distress syndrome, is also indicated.

Initial Antibiotic Therapy.

Rationale -

Common organisms are S. pneumoniae, N. meningitidis, and H. influenzae type b.

Pneumococcus - sensitive to penicillin and cephalosporins

N. meningitidis - penicillin and cephalosporins,

Some H. influenzae type b produce b-lactamases and therefore are resistant to

ampicillin. These b-lactamase-producing strains are sensitive to the cephalosporins.

Third-generation cephalosporins = ceftriaxone (100 mg/kg/24 hr administered once per

day or 50 mg/kg/dose, given every 12 hr),

Duration of Antibiotic Therapy =10-14 days.

Intravenous penicillin (400,000 U/kg/24 hr) for 7 days is the treatment of choice for

uncomplicated N. meningitidis meningitis.

Uncomplicated H. influenzae type b meningitis - for 10 days. ampicillin (200 mg/kg/24

hr, given every 6 hr) should be given with ceftriaxone or cefotaxime if H influenza is

isolated

Partially treated meningitis with clinical suspicion but not with CSF evidence -

ceftriaxone or cefotaxime for 10 days.

If child does not respond to treatment, a parameningeal focus may be present and a CT

or MRI scan should be performed.

repeat LP is not indicated in patients with uncomplicated meningitis

Gram-negative bacillary meningitis should be treated for 3 wk or for at least 2 wk after

CSF sterilization

Side effects of antibiotic therapy of meningitis -

phlebitis,

drug fever,

rash, emesis,

oral candidiasis,

diarrhea.

Ceftriaxone may cause reversible gallbladder pseudolithiasis, detectable by abdominal

ultrasonography. This may produce emesis and right upper quadrant pain.

Corticosteroids.

Rapid killing of bacteria releases toxic cell products after cell lysis (cell wall endotoxin)

that precipitates the cytokine-mediated inflammatory response. The resultant edema

formation and neutrophilic infiltration may produce additional neurologic injury

intravenous dexamethasone, 0.15 mg/kg/dose given every 6 hr for 2 days, in the

treatment of children older than 6 wk with acute bacterial meningitis, especially for H.

influenzae type b.

Corticosteroid administration -

decreases fever

lowers CSF protein and lactate levels

reduction in permanent auditory nerve damage

Corticosteroids have maximum benefit if given just before antibiotics and should be

administered with 1-2 hr of antibiotics.

Complications steroid - include gastrointestinal bleeding, hypertension, hyperglycemia,

leukocytosis, and rebound fever after the last dose.

dexamethasone for longer than 2 days offers no benefit, may cause gastrointestinal

bleeding.

Supportive Care.

identify early signs of cardiovascular, CNS, and metabolic complications.

Pulse rate, blood pressure, and respiratory rate should be monitored

Neurologic assessment, including pupillary reflexes, level of consciousness, motor

strength, cranial nerve signs, and evaluation for seizures,

Important laboratory studies include -

blood urea nitrogen;

serum sodium, chloride, potassium, and bicarbonate

urine output and specific gravity

complete blood and platelet counts

coagulation factors (fibrinogen, prothrombin, and partial thromboplastin times) in the

presence of petechiae, purpura, or abnormal bleeding.

Patients should initially receive nothing by mouth = vomiting may cause aspiration.

intravenous fluid administration should be restricted to one half to two thirds of

maintenance  - 1,000 mL/ sq mt /24 hr

Fluid administration may be returned to normal (1,500 mL/ sq mt /24 hr) when serum

sodium levels are normal. (10 kg = 0.3 sq mt, 20 kg = 0.6 sq mt, 30 kg = 1.0 sq mt)

Fluid restriction is not appropriate in the presence of systemic hypotension.

shock must be treated to prevent brain and other organ dysfunction (acute tubular

necrosis, adult respiratory distress syndrome)

septic shock require fluid resuscitation and therapy with vasoactive agents such as

dopamine, epinephrine, and sodium nitroprusside

Treatment of neurological complications - increased ICP with subsequent herniation,

seizures, and an enlarging head circumference due to a subdural effusion or

hydrocephalus. Signs of increased ICP (other than a bulging fontanel or isolated coma)

should be treated with endotracheal intubation and hyperventilation (to maintain the P

CO2 at approximately 25 mm Hg).

To reduce ICP

1. intravenous furosemide (Lasix, 1 mg/kg) Furosemide may reduce brain swelling by

venodilation and diuresis

2. mannitol (20% solution - 7 ml/kg in 20 minutes) mannitol produces shifting of fluid

from the CNS to the plasma and excretion during an osmotic diuresis.

Seizures

intravenous diazepam (0.2 mg/kg/dose) slowly.

Serum glucose, calcium, and sodium levels - determine if hypoglycemia, hypocalcemia,

or hyponatremia is precipitating seizures.

Then give- phenytoin (15-20 mg/kg loading dose, 5 mg/kg/24 hr maintenance) to

reduce recurrence. Phenytoin is preferred to phenobarbital because it produces less CNS

depression

COMPLICATIONS

Neurological complications -

seizures

increased ICP

cranial nerve palsies

stroke

cerebral or cerebellar herniation

transverse myelitis

ataxia

thrombosis of dural venous sinuses

subdural effusions = Collections of fluid in the subdural space in infants. - result in a

bulging fontanel, diastasis of sutures, enlarging head circumference, emesis, seizures,

fever, and abnormal results of cranial transillumination. CT or MRI scanning confirms the

presence of a subdural effusion. symptomatic subdural effusion should be treated by

aspiration through the open fontanel. Fever alone is not an indication for aspiration.

SIADH - results in hyponatremia and reduced serum osmolality This may exacerbate

cerebral edema , produce hyponatremic seizures

Fever associated with bacterial meningitis usually resolves within 5-7 days of the onset

of therapy.

Prolonged fever is due to

intercurrent viral infection

nosocomial or secondary bacterial infection

thrombophlebitis

drug reaction

Pericarditis or arthritis

Thrombocytosis, eosinophilia, and anemia may develop during therapy for meningitis.

Anemia may be due to hemolysis or bone marrow suppression.

DIC seen in cases with shock and purpura

PROGNOSIS.

The highest mortality - - pneumococcal meningitis.

neurodevelopmental sequelae =mental retardation seizures

cognitive or intellectual impairment,

sensorineural hearing loss -labyrinthitis following cochlear infection- dexamethasone

reduces the incidence of severe hearing loss Æ audiologic assessment before or soon

after discharge from the hospital,

delay in acquisition of language

visual impairment

behavioral difficulties

The prognosis is poorest among infants younger than 6 mo

seizures occurring more than 4 days after starting treatment, coma or focal neurological

signs at the time of presentation have more long-term sequelae.

Repeated meningitis - three distinct patterns.

1. Recrudescence is reappearance of infection during therapy CSF culture reveals the

growth of bacteria that have developed antibiotic resistance.

2. Relapse occurs between 3 days and 3 wk after therapy and represents persistent

bacterial infection in the CNS (subdural empyema, ventriculitis, cerebral abscess) or

other site (mastoid, cranial osteomyelitis, orbital infection). Relapse is often associated

with an inadequate choice, dose, or duration of antibiotic therapy.

3. Recurrence is a new episode of meningitis due to reinfection with the same bacterial

species or another pyogenic pathogen.

Recurrent meningitis suggests the presence of an acquired or congenital anatomic

communication between the CSF and a mucocutaneous site or defects in immune host

defense

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