Bacterial Meningitis in Children

Dr Rajesh KumarMD (PGI), DM (Neonatology) PGI, Chandigarh, IndiaRani Children Hospital, Ranchi

Inflammatory disease of the leptomeninges– three parts: the pia, arachnoid, and dura maters– Meningitis reflects inflammation of the arachnoid

mater and the cerebrospinal fluid (CSF) in both the subarachnoid space and in the cerebral ventricles.

Suspected bacterial meningitis is a medical emergency,

Organisms

1 month to 2 years — The major causes were S. pneumoniae (45 percent), Neisseria meningitidis (30 percent), and group B streptococcus (18 percent). 2 through 18 years — N. meningitidis was the most common cause, accounting for 59 percent of cases, followed by S. pneumoniae (approximately 25 percent) and Hib (approximately 8 percent).

Organisms

H influnzaePneumococcusN meningitidisIn <3 months: E.coli, Listeria

Clinical Features

Two patterns– Develops progressively over one or several days and

may be preceded by a febrile illness. – Acute and fulminant, with manifestations of sepsis

and meningitis developing rapidly over several hours. The rapidly progressive form is frequently associated with brain edema

Symptoms

Depends upon age– Infants, 1-5 years, >5 years

Fever Symptoms and signs of meningeal inflammation (nausea, vomiting, irritability, anorexia, headache, confusion, back pain, and nuchal rigidity)

Clinical features

In one review of 1064 cases of acute bacterial meningitis in children older than 1 month, 16 (1.5 percent) had no meningeal signs during their entire period of hospitalization Kernig sign — With the hip and knee flexed at 90º, cannot extend the knee more than 135º and/or there is flexion of the opposite knee Brudzinski sign — Brudzinski sign is present if the patient, while in the supine position, flexes the lower extremities during attempted passive flexion of the neckSigns of meningeal irritation are present in 60 to 80 percent of children with bacterial meningitis at the time of presentation and in approximately 25 percent of children with normal CSF findings Bulging fontanel was present in 20 percent of infants with meningitis, but also in 13 percent of infants with normal CSF and viral infections other than meningitis

Clinical features

Papilledema, which takes several days to become apparent, is an uncommon finding in acute bacterial meningitis. The finding of papilledema should prompt evaluation for venous sinus occlusion, subdural empyema, or brain abscess, TBM Signs of increased intracranial pressure that may occur in bacterial meningitis include palsies of the third, fourth, and sixth cranial nerves Seizures — Seizures, typically generalized, occur before admission to the hospital or within the first 48 hours of admission in 20 to 30 percent of patients with meningitis. Seizures later in the course are more often focal and may indicate cerebral injury

Focal findings — In one review of 235 children with bacterial meningitis, focal neurologic findings (hemiparesis, quadriparesis, facial palsy, visual field defects) were present at the time of admission in 16 percent of patients overall and in 34 percent of those with pneumococcal meningitis. The presence of focal neurologic signs at the time of admission correlated with persistent abnormal neurologic examination one year after discharge and with cognitive impairment.

History

The course of illness The presence of symptoms consistent with meningeal inflammation. The presence of seizures, an important prognostic finding. The presence of predisposing factors Immunization history Recent use of antibiotics, which may affect the yield of blood and/or CSF culture.

Examination

Vital signs: volume status, presence of shock, and the presence of increased intracranial pressure. The constellation of systemic hypertension, bradycardia, and respiratory depression (Cushing triad) is a late sign of increased intracranial pressure.Head circumference should be measured at the time of admission in children younger than 18 months of age Elicitation of meningeal signs Cutaneous examinations are discussed above. Other bacterial infections (eg, facial cellulitis, sinusitis, otitis media, arthritis, pneumonia).

Lab evaluation

Blood cultures: positive in at 50 % of patients. Among children who were not pretreated with antibiotics.Contraindications to LP:– cardiopulmonary compromise, – increased intracranial pressure, – papilledema, – altered respiratory effort, – focal neurologic signs, – skin infection over the site for LP

CSF culture may be positive in the absence of pleocytosis

CSF

TLC:typically >1000 WBC/microL, with a predominance of neutrophils .A CSF WBC count >6/microL is considered abnormal in children older than 3 months of age Traumatic LP: should be treated presumptively for meningitis pending results of CSF culture.The presence of a single neutrophil in the CSF is considered abnormal Glucose: <40 mg/dL in > 50% cases. ratio of the CSF to blood glucose concentration is usually depressed (<0.66)Protein:100 to 500 mg/dL

CSF CRP

100 % sensitive and 96-100 % specific-ve CRP rules out bacterial meningitis

Role of urine culture

Urine cultures should be obtained in infants (<12 months of age) who present with fever and nonspecific symptoms and signs of meningitis since urinary tract infection may be the primary source of the meningitis pathogen in such patients

Neuroimaging

Indications for imaging before LP in children with suspected bacterial meningitis include– Coma– The presence of a CSF shunt – History of hydrocephalus – Recent history of CNS trauma or neurosurgery– Papilledema – Focal neurologic deficit (with the exception of palsy of cranial

nerve VI [abducens nerve] or VII [facial nerve])

Bacterial Meningitis Score

Positive CSF Gram stain CSF absolute neutrophil count of <1000 cells/microL CSF protein of at least 80 mg/dL Peripheral blood ANC of at least 10,000 cells/microL History of seizure before or at the time of presentation

Absence of all these excludes bacterial meningitis

Treatment: General Principle

Avoidance of delayEmperical antibiotic

Drug entry into CSF —Most drugs reach peak concentrations in the CSF that are only 10 to 20 percent of peak concentrations in the serum. This is because the blood-brain barrier blocks macromolecule entry into the CSF, with small, lipophilic molecules penetrating most easily.The peak concentration of drugs in CSF increases with inflammation of the blood-brain barrier. The mean CSF/serum ratio two hours after administration of the same intravenous dose of penicillin was 42 percent on the first day of therapy but fell to less than 10 percent on the tenth day, when the inflammatory changes had subsided

Immediate management

Assurance of adequate ventilation and cardiac perfusion. Initiation of hemodynamic monitoringEstablishment of venous access. Administration of fluids as necessary to treat septic shock, if present. Administration of dexamethasone if warranted. before or immediately after the first dose of antimicrobial therapy.Administration of the first dose of empiric antibiotics Administration of glucose (0.25 g/kg) for documented hypoglycemia (serum glucose concentration less than 40 mg/dL Treatment of acidosis and coagulopathy

Supportive careFluid and electrolyte management —– Isotonic fluid to maintain blood pressure and cerebral perfusion. – Children who are hypovolemic, but not in shock, should be rehydrated

with careful and frequent attention to fluid status. – For children who are neither in shock nor hypovolemic, moderate fluid

restriction (1200 mL/m2 per day) initially, especially if the serum sodium is less than 130 meq/L. Fluid administration can be liberalized gradually as the serum sodium reaches 135 meq/L. Most children can receive maintenance fluid intake within 24 hours of hospitalization.

Monitoring —– increased intracranial pressure, seizure activity, development of

infected subdural effusions, particularly during the first two to three days of treatment,

– Heart rate, blood pressure, and respiratory rate should be monitored regularly with a frequency appropriate to the care setting.

– A complete neurologic examination should be performed daily; rapid assessment of neurologic function should be performed several times per day for the first several days of treatment.

– Head circumference should be measured daily in children younger than 18 months

In US (nelson)– 25-50% S.pneumoniae resistant to penicillin– 25 % S Pneumoniae resistant to cefotax or

ceftraixone– 30-40 % Hib resistant to ampicillin

In INDIA ?

JIPMER Study

Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens were H. influenzae (17%) and S. pneumoniae (12%). RESULTS: The illness at presentation was mild in 13% and severe in 36% of cases. The

Emperic Therapy

empiric regimen should include coverage for Hib, penicillin resistant S. pneumoniae and N. meningitidis. E.coli in young infantsHigh dose of 3rd generation cephalosporin + Vancomycin

Dexamethasone

Animal studies:hearing loss is associated with the severe inflammatory changesRCT and meta-analyses indicate that dexamethasone therapy provides no survival advantage in children, but reduces the incidence of deafness and severe neurologic complications in selected children, predominantly those with meningitis caused by Hib. The data are insufficient to demonstrate a clear benefit in children with pneumococcal meningitis before or within one hour of the first dose of antibiotic therapyconcern that the CSF concentration of vancomycin may be diminished when administered with dexamethasone > 6 weeks of age0.15 mg/kg per dose) every 6 hours for 2 to 4 days

Duration of treament

S. pneumoniae: 10-14 daysN. meningitidis: 5-7 daysHib: 7-10 daysGram –ve: 3 weeksCSF analysis near the end of therapy, particularly in young infants, needs longer therapy if– Percentage of neutrophils >30 percent, – or CSF glucose concentration <20 mg/dL

Out patient therapy

Completion of at least 6 days of inpatient therapyAfebrile for at least 24 to 48 hours before initiation of outpatient therapy. No significant neurologic dysfunction or focal findings. No seizure activity. Clinical stability.

Response to therapy

duration of fever is typically four to six days after the initiation of adequate therapy Persistence of fever beyond 8 days and secondary fever have a number of causes, including:– Inadequate treatment– Development of nosocomial infection – Discontinuation of dexamethasone – Development of a suppurative complication (pericarditis,

pneumonia, arthritis, subdural empyema)– Drug fever (a diagnosis of exclusion)

Repeat CSF

Poor clinical response after 24-36 hours of antibioticsPersistence or recurrence of feverGram –ve meningitis

Neuroimaging

Focal neurologic signs, increasing head circumference, or prolonged obtundation, irritability, or seizures (>72 hours after the start of treatment); Persistently positive CSF cultures despite appropriate antibiotic therapy Persistent elevation of CSF neutrophils at the completion of standard duration of therapy (more than 30 to 40 percent) Recurrent meningitis

Prognosis

Mortality:meta-analysis: 4520 children 4.8 %in developed countries and 8.1 % in developing countries Hib:3.8 %, N. meningitidis: 7.5 %, S. pneumoniae: 15.3 %Neurological sequele:16% in developed and 26 % in developing countries– Deafness — 11 percent, including bilateral severe or

profound deafness in 5 percent– Mental retardation — 4 percent – Spasticity and/or paresis — 4 percent – Seizures — 4 percent

Poor prognostic factors

Etiology: more with pneumocaccalSeizure after 72 hoursCSF sugar < 20 mg per dl at admissionDelayed sterlization of CSF : > 24 hours

Untreated meningitis as hydrocephalus

infantile hydrocephalus due to clinically unsuspected meningitis.8 year study period 54.2% (39/72) of hydrocephalus were found to be due to infection, far higher than what is reported from developed nationsit may be a good practice to sample the CSF in every infant with hydrocephalus before a shunting

Long-term Disability Following Neonatal and Infantile Meningitis -results at 5 years of age

Disability Neonates Infants Controls

n=274(%) n=1304(%) n=1391(%)

Severe 20 (7.3)* 72 (5.5) 1 (0.1) – p<0.0001

Moderate 50 (18.2)** 103 (7.9) 20 (1.4) – p<0.0001

Mild 66 (24.1) 392 (30.1) 275 (19.8)

None 138 (50.4) 737 (56.5) 1095 (78.7)

 * not significant. ** p<0.001

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Inci

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• Currently licensed vaccine is composed of elements of polysaccharide coat of the bacteria

• Serogroups A, C, W-135, and Y

• Recommended for control of serogroup C meningococcal disease outbreaks although its not guaranteed to control them

• Recommended for use among certain high risk-groups

Meningococcal Vaccination

• Vaccine may benefit travelers to countries in which disease is hyperendemic or epidemic

• A poor vaccine in children <18-24 months

• Immunity of limited duration, especially in young children. Only 2-3 years at best.

• Vaccine confers effective protection

• Protective levels of antibody are usually achieved within 7-10 days