Meningitis is the most common case asked in almost all USMLE exams

 

A Case of Bacterial Meningitis

Bacterial meningitis affects 1 in 500 children younger than 2 years. Meningitis most commonly presents with subtle signs and symptoms that may easily be mistaken for a benign childhood illness.

Etiology of Bacterial Meningitis

Neonatal Meningitis.

Infancy

Childhood

Streptococcus agalactiae (group B streptococcus) and Escherichia coli cause three fourths of all infections in the neonate. Prematurity is the greatest risk factor for infection in neonates

In infants, Haemophilus influenzae is the most common bacterium causing meningitis. The widespread use of H. influenzae type B (HiB) conjugate vaccines has decreased the incidence of HiB meningitis by 95%.

The frequency of meningitis decreases markedly in children older than 2 years, and it remains at a relatively constant level until adulthood.

Etiologies include H influenzae, S pneumoniae, and N meningitidis.

 

Infant 0 to 1 month

Common: Group B streptococci, E coli, other aerobic gram-negative bacilli

Uncommon: Listeria monocytogenes, Enterococcus sp.

Infants 1-3 Months

Common: H influenzae (HiB), S pneumoniae, N meningitidis

Uncommon: Group B streptococci, E coli, Listeria monocytogenes, Salmonella sp.

3 Months and Older

Common: H influenzae, S pneumoniae, N meningitidis

Uncommon: Salmonella sp.

CSF Shunt

Common: Usual organisms for age, Staphylococcal sp.

 

Pathophysiology of Bacterial Meningitis
Pathogens invade the central nervous system by hematogenous dissemination after bacterial colonization of the nasal pharynx or by direct spread from a distant focus of infection, such as the mastoid air cells or paranasal sinuses.
Endotoxin from Gram-negative organisms and peptidoglycan from Gram-positive organisms evoke the production of interleukin 1 (IL1) and tumor necrosis factor (TNF) by CNS macrophages. These cytokines cause endothelial cells to produce prostaglandin E2 (PGE2).
PGE2 is a potent chemotactic stimulus for polymorphonuclear leukocytes, which increase blood-brain barrier permeability. The neutrophilic pleocytosis can obstruct cerebrospinal fluid (CSF) outflow, resulting in increased intracranial pressure. Endothelial injury can lead to cerebral hypoxia.

 

Signs and Symptoms of Meningitis
Newborns
In the newborn, signs and symptoms of bacterial meningitis are often very similar to those of sepsis or other serious illnesses.
Neonates with acute bacterial meningitis often lack meningismus. Meningitis may manifest as hyperthermia or hypothermia, poor feeding, listlessness, lethargy, irritability, vomiting, or respiratory distress. A bulging fontanelle may be seen in up to one-third of cases, although it usually appears later in the course of illness.
In infants, the depressed central nervous system function is manifest by a lack of motor response to stimuli (not using the muscles of the head and shoulders) by the primary caregiver, often described as the "infant not being consolable" or "not responding to the mother."
Evaluation of the febrile (or hypothermic) ill newborn requires a lumbar puncture.

Older Infants and Children

In older infants and children, initial symptoms of bacterial meningitis consist of fever, signs of increased intracranial pressure, and cerebral dysfunction. The fever in children who have bacterial meningitis usually is greater than 38.3 degrees C.

Increased intracranial pressure initially is manifested as vomiting and lethargy. Older children and adolescents frequently present with headache, fever, altered sensorium, and meningismus. Kernig's or Brudzinski's signs may be absent in 50% of adolescents and adults with bacterial meningitis.

How do you diagnose meningitis?

Meningitis is frequently associated with acute otitis media, pneumonia, and even gastroenteritis. The most important consideration in suspecting acute bacterial meningitis in the child or infant is his interaction with the environment. The child who is difficult to console, paradoxically irritable (increasingly agitated with parental comforting), or appears toxic should be suspect.

Lumbar puncture is recommended in the young child or infant who fails to follow your examination or who interacts inappropriately.

All febrile neonates less than 2 months of age should undergo a full septic work-up, with initiation of empiric antibiotic treatment. This evaluation includes bacterial cultures of urine, blood, and CSF.

Children between 2 and 24 months old. In these younger children, the initial presentation of early meningitis is often non-focal, with fever, lethargy, irritability, and/or vomiting. Only 48% of infants with bacterial meningitis will have positive meningeal signs, including nuchal rigidity or Kernig's or Brudzinski's signs. A high index of suspicion for meningitis is essential when evaluating the febrile infant 12 months of age or younger.

Lumbar Puncture

Analysis of CSF by LP is the basis for evaluation of suspected meningitis. A CT scan is not necessary prior to an LP In children without evidence of increased intracranial pressure, focal neurological findings, or papilledema.

If increased intracranial pressure is suspected, LP should be postponed, a blood culture obtained and empiric antimicrobial therapy initiated while the CT scan is pending.

CSF studies include cell count, protein, glucose, bacterial culture, and Gram's stain. Opening pressures are helpful in older children and adults, but they are usually not obtained in the infant age group. Prior administration of antibiotics has minimal effect on CSF findings in bacterial meningitis.

CSF glucose of less than 40 mg/dL or a CSF glucose-to-blood glucose ratio of less than 0.3-0.5 suggests bacterial meningeal infection, as does a CSF protein of more than 150-170 mg/dL in neonates, or 40-50 mg/dL in older infants and children. In HIV-positive children, India ink, cryptococcal antigen, acid fast bacillus (AFB) smear and culture, and fungal cultures are obtained. Children with a history of tuberculosis exposure or travel to an area endemic for tuberculosis should have a CSF AFB smear and culture.

Higher WBC counts (>1000 cell/mm3) with a predominance of polymorphic neutrophils (PMNs) are associated with bacterial meningitis; however, a finding of fewer WBCs (or <50% PMNs) may be seen with early bacterial disease.

A small number of patients with bacterial meningitis may present with normal CSF indices. Therefore, a child who clinically appears ill, even with a normal spinal fluid analysis, mandates immediate empiric antimicrobial therapy and hospital admission. Repeat LP 12-24 hours later may reveal a conversion to CSF indices consistent with bacterial infection.

Disorder

Color

WBC Count (/mm3)

Glucose (mg/dL)

Protein (mg/dL)

Gram's Stain

Culture

Normal infant

clear

<10

>40

90

negative

negative

Normal child or adult

clear

0

>40

<40

negative

negative

Bacterial meningitis

cloudy

200-10000

<40

100-500

usually positive

positive

Viral meningitis

clear

25-1000

(<50% PMN)

>40

50-100

negative

negative

Cryptococcal meningitis

clear

50-1000 (<50% PMN)

< 40

50-300

negative

negative

 

Associated Diagnostic Work-up

Complete blood count (CBC) should be obtained, but a normal WBC count does not exclude a significant bacterial infection. Serum electrolytes and glucose are obtained as a baseline and to exclude the syndrome of inappropriate antidiuretic hormone (SlADH).

Bacterial antigen tests of CSF (latex agglutination and counter immunoelectrophoresis) are usually of little value. However, children on antibiotics for another focus of infection who present with partially treated meningitis, may have falsely negative cultures, and latex agglutination or other rapid antigen detection test may yield a diagnosis. False-positive and false-negative results are common.

Blood cultures are obtained to rule out sepsis or bacteremia and to increase the diagnostic yield for a bacterial pathogen.

Treatment of Meningitis

Antibiotics

Antibiotics should be initiated immediately on suspicion of bacterial meningitis. Initial agents are chosen empirically because culture results will not be available for 24 hours.

In neonates without grossly purulent CSF, ampicillin and gentamicin are the agents of choice while awaiting culture results.

Three weeks of parenteral therapy is required.

Patient Group

Antibiotic

Neonates

Ampicillin plus gentamicin, or ampicillin plus cefotaxime

Infants (1-3 months)

Ampicillin plus cefotaxime

3 months to adult

Cefotaxime or ceftriaxone

Immunocompromised patients

Cefotaxime or ceftriaxone plus ampicillin (plus aminoglycoside)

Neurosurgery, head trauma

Cefotaxime or ceftriaxone plus nafcillin (plus aminoglycoside)

Chronic CSF fistula

Cefotaxime or ceftriaxone plus nafcillin

 

Organism

Antibiotics

H influenzae

Cefotaxime or ceftriaxone; ampicillin (if sensitive); chloramphenicol

S pneumoniae

Reduced Penicillin Sensitive

Penicillin Resistant

Penicillin G; cefotaxime or ceftriaxone; chloramphenicol

Cefotaxime or ceftriaxone

Cefotaxime or ceftriaxone plus rifampin or vancomycin

N meningitides

Penicillin G, or chloramphenicol

S agalactiae

Penicillin G or ampicillin

L monocytogenes

Ampicillin (plus aminoglycoside) or trimethoprim/sulfamethoxazole

Enterobacteriaceae

Cefotaxime or ceftriaxone plus aminoglycoside

Pseudomonas aeruginosa

Ceftazidime plus aminoglycoside

S aureus

Nafcillin

Supportive Care

Maintenance of normal blood glucose, appropriate blood volume, blood pressure and oxygenation, and management of increased intracranial pressure have a greater impact on outcome than the specific antibiotic chosen.

Restricting fluids to two-thirds maintenance, after the intravascular volume has been replaced, is recommended to prevent cerebral edema.

Dexamethasone

Administration of dexamethasone during the treatment of H influenzae meningitis reduces the incidence of subsequent sensorineural hearing loss.

Dexamethasone is administered to children older than 3 months of age with bacterial meningitis. The dosage is 0.15 mg/kg IV q6h for the first 4 days. The effect is maximized if it is administered 10 minutes before the first dose of antibiotics.

Acute Complications of Bacterial Meningitis

Cerebral Edema

Within the first 2 days of bacterial meningitis, the most common complication is cerebral edema. Restricting fluids to two-thirds maintenance after intravascular volume has been restored will minimize the likelihood of cerebral edema.

Increased intracranial pressure, secondary to cerebral edema manifests as coma, absence of a oculocephalic reflex (ie, fixed response to the doll head maneuver), or fixed eye deviation. Increased intracranial pressure is managed with mannitol and surgical decompression. Acute intervention is warranted to avoid cerebral or cerebellar herniation.

Subdural Empyema

Subdural empyema usually occurs in infants with severe Gram-negative meningitis. Coma and increased intracranial pressure with intermittent decorticate posturing may be followed by seizures.

Cranial computed tomography with contrast will reveal a subdural collection of fluid.

Ventriculitis

Ventriculitis is a common complication of Gram-negative and group B streptococcal meningitis in neonates.

This disorder is manifest by clinical worsening in a neonate being treated with appropriate antibiotics whose CSF sampled from the lumbar area shows improvement. Apneic spells and bradycardia often occur.

Cranial CT may identify fluid of different contrast densities in the ventricles. The diagnosis is confirmed by ventricular puncture.

Brain Abscess is an uncommon complication of bacterial meningitis; it most commonly occurs as a complication of H influenzae disease and is manifested by a focal motor deficit.

Chemoprophylaxis for Pediatric Meningitis

Haemophilus Influenzae (HiB)

Household contacts should receive rifampin only if there is one or more child less than 4 years of age living in the household. All members of the household, including those previously immunized, and the patient should receive prophylaxis with rifampin.

Daycare contacts may receive prophylaxis if two or more cases of invasive HiB disease occur within two months. In smaller daycare settings with children <2 years, prophylaxis after a single case may be recommended.

Rifampin Prophylaxis: 20 mg/kg single daily dose (maximum, 600 mg/d) PO for four days.

Neisseria Meningitidis

All household and daycare contacts, and anyone with close contact with oral secretions should receive prophylaxis.

Rifampin Prophylaxis: 20 mg/kg/d (maximum, 600 mg/d) q12h PO for two days.

Streptococcus Pneumoniae. Chemoprophylaxis is not indicated. §