PYOGENIC MENINGITIS

KINDU W., MD

Central Nervous System Infections

• When acute, the most common causes of fever associated with signs and symptoms of CNS disease in children.

• Specific microbes depend on : age, immune status, epidemiology of the pathogen.

• In general, viral causes > bacterial > fungal & parasitic.

• May be diffuse (meningitis, encephalitis) or focal. • Diagnosis depends on careful examination of CSF.

Acute Bacterial Meningitis Beyond The Neonatal Age• One of the most potentially serious infections in

infants & older children,• High rate of acute complications & risk of long

term morbidity [deafness]

• Etiology in the neonatal age distinct from older children – may overlap in 1-2 mo olds:

GBS, S. pneumoniae, N. meningitidis, Hemophilus Influenzae type B (HIB).

Etiology

• 1st 2 mo of age- GBS, Gram negative enteric bacilli, & L.monocytogenes.

• 2 mo- 12 yr- S.pneumoniae, N.meningitidis, HIB. • ~ 70% of cases among <5 yr were due to HIB.

• P. aeruginosa, S. aureus, CONS, Salmonella spp – less common & occur with altered host defense.

Epidemiology

• Major risk factor – lack of immunity to specific pathogens associated with young age.

• Additional risk factors –

- recent colonization with pathogenic bacteria,

- close contact with patient having invasive disease by N. meningitidis & HIB,

- crowding and poverty.

Meningitis…

• Mode of transmission-

person to person contact thru respiratory tract secretions or droplets.

• Specific host defense defects:

- altered Ig production encapsulated org.,

- defects of the complements recurrent meningococcal infection,

- splenic dysfunction – Pneumococcal, HIB

Meningitis…

- T- lymphocyte defects- L.monocytogenes,

- CSF leak (congenital/acquired) ↑ risk of pneumococcal, staphylococcal, gram neg. enteric bacilli. [neural tube defect, basal skull fracture]

- defects of the properidine system – lethal meningococcal disease.

Etiologies (common):

• Neisseria meningitidis - serotypes A,B,C,W135,& Y;

- sporadic or epidemic;

- in developing countries, epidemics due to serogroup A.

- more common in the winter & spring,

- infections acquired from a contact- daycare facility, colonized adult or a patient.

Meningitis…

• Hemophilus influenzae type b – HIB

- Primarily in infants 2 mo- 2yr, 50% of cases occurred in the 1st yr of life,

- risk increased among family or daycare center contacts of patients.

Pathogenesis

• Hematogenous – most common:

bacterial colonization of nasopharynx attach to mucosal epith.cell receptors by pili breach mucosa& enter circulation large capsules interfere phagocytosis to CSF thru choroid plexus of ventricles extracerebral CSF & subarach space bacterial proliferation inflammation-cytokines

Cont…

• Rarely contiguous: -

- paranasal sinusitis, otitis media, mastoiditis, orbital cellulitis, or cranial/ vertebral osteomyelitis,

- penetrating trauma.

Pathogenesis of Meningococcal Infections

Pathology & Pathophysiology• Meningeal exudate- around the cerebral veins,

venous sinuses, convexity of the brain, cerebellum, in the sulci, basal cisterns– [thrombosis>stasis>focal ischemia> focal neurologic

deficit]

• Ventriculitis;• Cerebral infarction- vascular occlusion due to

inflammation, vasospasm,& thrombosis;• Inflammation of spinal nerves & roots- meningeal

signs.

Cont’d

• Inflammation of cranial nerves- neuropathy of CN I, III, VII, VIII; [deafness]

• Increased ICP - cytotoxic cerebral edema (due to cell death) - vasogenic – increased cap. vascular

permeability - interstitial– increased hydrostatic pressure

Cont’d• SIADH- Syndrome of Inappropriate ADH secretion-

adds on the risk of ICP;

• Hydrocephalus- communicating (due to thick subarachinoid exudates) & less commonly obstructive (acqueductal stenosis);

• Subdural effusionsdamage to the cerebral cortex

Clinical manifestationsTwo dominant patterns- Meningococcemia • 1. dramatic, sudden onset, rapidly progressive with

shock, purpura, DIC, and coma- resulting in death within 24 hrs

• less common

• 2. Several days of fever, poor feeding, myalgia, arthralgia, skin rash (non specific);

• Meningeal irritation signs- neck stiffness, kerning, brudzinsky's (<12-18mo inconsistent).

fulminant meningococcemia with extensive purpuric patches.[as opposed to vasculitis, these purpuric lesions are non-blanching b/c they are actual hemorrhages]

Cont’d

• Signs of increased ICP -emesis, bulging fontanel, CN III,VI palsy, Cushing triad [hypertension bradycardia, apnea or hyperventilation,] posturing, stupor, coma, +/- signs of herniation

- focal neurologic signs occur in 10-20% • Seizure (focal/ generalized)- due to cerebritis,

infarctions, E’abnormality (20-30% of patients).

Diagnosis:• WBC count & differential,• Confirmed by CSF analysis:- ↑ opening pressure - turbid/frank pus- 200-400/mm3 - neutrophilic pleocytosis- cells >1000/mm3,

75-95% neutrophils,- elevated protein- 100-500mg/dl,- reduced glucose- [due to ↓sed transport across BBB]- gram stain(70-90% positivity) & - Culture & sensitivity.

LP is contraindicated if: - ↑ ICP (other than a bulging fontanel)- evidenced by

3rd/6th nerve palsy, hypertension & bradycardia with respiratory abnormality,

- severe cardiopulmonary compromise, - infection of the skin on the LP site,

- thrombocytopenia- relative contraindication.

• Blood culture- positive in 80-90% of cases

• LAT- in case of prior antibiotic use• [latex agglutiniation test –doesn require whole

cells. Detects cell fragment]

Differential diagnosis• Viral meningoencephalitis - less ill- classic CSF profile:

- normal/mild inc. pressure

- mononuclear cells, <1000/mm3

- protein usu. 50-200mg/dl

- glucose- normal.

Partially treated bacterial meningitis-cells 5-10000/mm3,

-glucose normal/decreased, culture negative

-LAT positive

Treatment

• Rapidly progressing disease of <24hrs- - immediate antibiotics after LP - Rx of ↑ ICP - Rx of shock, ARDS• More protracted subacute course - evaluate for signs of ↑ ICP & focal

neurologic signs to decide on LP.

Rx cont’d

- initial antibiotic Rx - emperical choice of therapy- primarily determined by the susceptibility of S. pneumoniae:

.25-50% - resistant to penicillin & up to 25% are resistant to cefotaxime & ceftriaxone

.most N.meningitidis- sensitive to penicillin & cephalosporins

.~30-40% of HIB- produce B-lactamase

Recommended emperical therapy

• Vancomycin(60mg/kg/24hr,given q 6hr) + cefotaxime(200mg/kg/24hr,given q 6hr) or ceftriaxone(100mg/kg/24hr,given q12hr)• Immunocomp.&suspected gram neg. ceftazidime/aminoglycoside added• Duration – S.pneumoniae- 10-14 days N.meningitidis- 5-7 days HIB- 7-10 days

Cont’d

- unknown etiology- 7-10 days - gram neg. bacilli- 3wk• Repeat LP recommended: - in some neonates, in gram neg. bacillary

meningitis, and B-lactam resistant pneumococcus.

Note: CSF should be sterile in 24-48 hrs of antibiotics initiation.

Corticosteroids

• Rapid killing of bacteria releases toxic cell products. This precipitates cytokine mediated infl. response- edema & neutro response. This will lead to additional neurologic injury with worsening of CNS sx:

-Dexamethasone- 0.15mg/kg/dose q6hr-2days (benefit max if given 1-2 hr before antibiotics)

- decreased permanent auditory nerve damage.

- CAUTION: make sure it’s not viral meningitis!

Supportive care

• NPO• IV fluid: 800-1000ml/m2/24hr(1/2-2/3rd of

maintenance)- shock treated aggressively.• Septic shock- dopamine• Signs of ↑ ICP-ET intubation & hyperventiln (PCO2~25mmHg)- IV lasix (1mg/kg), mannitol (0.5-1g/kg)• Seizures- first Rx-diazepam iv or lorazepam

cont’d

- do serum glucose, calcium, & sodium levels - After initial Rx, phenytoin (loading dose of 15-

20mg/kg, maintenance 5mg/kg/d)• Neurologic ass’t: esp.1st 72 hrs-PR, BP, RR, Level of consciousness, pupils, motor, Cranial nerves, Sz, Head circumference, Urine output.- Lab.- Sp. Gravity of urine

Complications

• Acute- Seizures, ↑ ICP, CN palsies, stroke, cerebral

& cerebellar herniation;- Subdural effusion- in 10-30%,

(asymptomatic in 85-90% of cases, esp in infants)- symptoms- bulging fontanel, enlarging HC,

emesis, Sz, fever, cranial trans-illumination- aspiration indicated in ↑ ICP/decreased LOC

Cont’d

• Syndrome of inappropriate ADH secretion- 30-50% of cases,

- hyponatremia, decreased serum osm.

- exacerbate cerebral edema, hyponatremic sz.• Pericarditis, arthritis- due to bacterial dissemination,

or immune cplx deposition.• DIC• Visual & hearing impairment, behavioral problems.

Prognosis

- MR- <10%- highest in pneumococcal- severe neurodevelopmental abn.-in 10-20%- Poor prognosis in: . < 6mo of age . >1mill.CFU bact./ml . Sz for >4 days into Rx . Coma/focal neurologic sign at admission

Prevention • Vaccination & antibiotic prophylaxis - N. meningitides- rifampin 10mg/kg/dose

q12 hrs for 2 days –for all close contacts of patients with meningococcal meningitis,

. Quadrivalent vaccine (A,C,Y,W135) for high risk children >2yr (in epidemics, immunocompromised, exposed contacts)

Vaccines:Polysaccharide vaccines are not effectively immunogenic. That’s why we do not give it at an earlier age like the rest of the vaccinesConjugate vaccines are composed of both protein and polysaccharide, which is sufficiently immunogenic.

Cont’d

- HIB -rifampin 20mg/kg/day, once, 4 days for all household contacts.

Conjugate vaccine -from 2mo of age - S.pneumoniae Heptavalent conjugate vaccine- from 2mo of

age.