BACTERIAL MENINGITIS

Bacterial meningitis (BM) is a potentially life-threatening CNS infection, characterized by primary inflammation of leptomeninges due to non-tubercular bacterial infections. Epidemiology: BM is more common in children lt;5 years.

(e) splenic dysfunction, e.g. asplenia or splenectomy,

(f) immunodeficiency disorders.

Recurrent meningitis may be seen in cases with—(a) CSF rhinorrhea following skull fractures involving cribriform plate or ethmoidal sinus, (b) lumbosacral dermal sinus, and (c) immunodeficiency disorders.

Etiology: Microbiology of BM depends on the age, source of infection and host-defence, as follows:

• In newborns and first 3 months of life, BM is usually caused by organisms from maternal flora, commonest being E. coli, Staph. aureus and enterococci (S. fecalis). Listeria monocytogenes is emerging as common pathogen in this age group. Group B streptococci, a common cause of neonatal meningitis in western countries, is uncommon in India.

• From 3 months to 3 years; H. influenzae B (HiB) is the commonest cause (~50%), followed by S. pneumoniae, Staph. aureus and N. Meningitides (usually in outbreaks). Incidence of Hib meningitis has declined due to widespread immunization.

• In older children gt;3 years; S. pneumoniae is the pre­dominant pathogen, write N. meningitides is common during outbreaks.

• Nosocomial or opportunistic meningitis may be caused by any prevalent hospital flora, e.g. Staph. aureus, coagulase-negative staphylococci, Pseudomonas, Klebsiella, Candida, etc.

Certain pathogens are more common in high-risk children, e.g. pneumococci in cases with ENT infections and CSF leak; capsular organisms like pneumococci, Hib and meningococci in splenectomized children; Staph.

Pathogenesis: Causative organisms reach the meninges via—(a) hematogenous spread from a distant septic focus, or (b) direct spread from colonized nasopharynx or neighboring infection, e.g. otitis media, cranial trauma or menigomyelocele. Inflammation of meninges initiates multiple pathological reactions, as follows:

• Extensive meningeal exudates, which tend to collect at the base of brain and block subarachnoid space, leading to hydrocephalus.

• Vasculitis and thrombosis of cerebral vessels, leading to parenchymal infarcts with localizing signs and residual sequelae.

• Cerebral edema, which may be vasogenic due to direct endothelial injury and increased vascular permeability or cytotoxic due to release of various chemical mediators, e.g. cytokines.

• Raised ICP due to-i) cerebral edema, (ii) CSF flow block, and (iii) water retention due to inappropriate ADH secretion (SIADH).

• Ventriculitis, leading to persistence of infection is more common in newborns and infants.

Clinical presentation depends on the age and causative organism, being more severe and acute in young and immunocompromised children. A typical case of BM presents with acute onset (usually lt; 72 hours) of:

• High fever with constitutional signs, e.g. irritability/ lethargy and anorexia.

• Signs of meningeal irritation, e.g. nuchal rigidity, Kernig's sign and Brudzinski's sign, though these signs are uncommon in infants.

• Signs of raised ICP, e.g. headache, vomiting, bulging anterior fontanel, widening of cranial sutures and

papilledema. irregular breathing, hypertension and bradycardia.

• Altered sensorium and coma due to cerebritis and cere­bral edema, along with decerebrate or decorticate posture.

• Focal neurological signs, e.g. cranial nerve palsies and motor deficits, are less common in BM (15-30%) than in tubercular meningitis.

• Seizures or status epilepticus due to cerebritis, infarcts and electrolyte disturbances (SIADH).

Unique features of BM due to specific organisms are as follows:

Hib meningitis is most common in 6 months - 2 years age group or in older children with splenic dysfunction. Subdural effusion is common, leading to persistent fever and neurological signs despite CSF clearance.

Meningococcal meningitis is usually seen in epidemics due to group A and C infections, while group B infections cause sporadic disease. Presence of petechial rash over skin/mucus membranes or circulatory shock (due to adrenal hemorrhage; Waterhouse-Friderichsen syndrome) is a strong indicator of meningococcal disease.

Pneumococcal meningitis is more common beyond infancy, frequently associated with ENT infections, head injury or splenic dysfunction, e.g. sickle cell disease. Subdural effusions are common.

Staphylococcal meningitis is common in newborns and young children with obvious septic focus, e.g. pneumonia or osteomyelitis. Toxic look, fulminant course and focal neurological signs due to sinus thrombosis are common.

Diagnosis of BM depends on:

• Clinical suspicion in a case with fever and neurological signs. Diagnosis is difficult in young infants due to absence of high fever and signs of meningeal irritation due to limited inflammatory response. Presence of neonatal sepsis (Ch 12.15.2) with—(i) vacant stare, (ii) seizures, (iii) irritability or drowsiness, and (iv) altered tone, should arouse suspicion of BM in this age group.

• CSF examination is baseline investigation in BM after excluding contraindications (Ch 18.2), revealing—(a) increased pressure (b) turbid appearance, (c) markedly high proteins (gt;200 mg/dl), (d) severe hypo- glycorrhoea, (CSF glucose lt;50% of blood glucose), and (e) marked polymorphonuclear pleocytosis (gt;200 cell/mm³). However, CSF findings in partially-treated cases or traumatic LP may be misleading due to altered biochemical/cellular values.

• CSF microbiology: Identification of causative pathogen in CSF by gram-staining and culture is essential for rational antimicrobial therapy, though it may be sterile after prior antibiotic therapy.

• Rapid diagnostic tests for causative pathogens in CSF are available, to detect presence of specific antigens (latex-agglutination test) or microbial DNA (PCR). These tests are specially useful to diagnose BM in partially treated cases.

• Neuroimaging with CT/MRI is necessary in non-res- ponders or those with low GCS (lt;12), status epilepticus, and/or focal signs to exclude complications, e.g. hydrocephalus, subdural effusions/empyema, cerebral infarcts, etc.

• Ancillary investigations, e.g. S. electrolytes (for SIADH) may be needed in some cases.

D/D of BM mainly includes:

• Meningism in apical pneumonia or inflammatory lesions of neck (normal CSF with no neurological findings except neck rigidity),

• Tubercular meningitis (see Table 18.30)

• Viral encephalitis (very acute onset, no signs of menin­geal irritation, sterile CSF).

• Aseptic meningitis (clinical picture and CSF findings suggestive of BM, with sterile CSF).

• Cerebral malaria (normal CSF and positive peripheral smear for parasites).

In addition, BM may also be confused with other causes of coma and seizures, including subarachnoid hemorrhage (no fever, hemorrhagic CSF) and focal CNS infections, e.g. brain abscess (localizing signs).

Management of BM includes—(a) specific antimicrobial therapy, and (b) supportive therapy.

I. Antimicrobial therapy: Empirical therapy with broad­spectrum IV antibiotics should be started immediately in all cases, which must be modified after culture and sensitivity reports are available. Choice of the antibiotics depends on probable cause and local microbial profile, modified after culture/sensitivity reports (Table 18.28).

After initiation of effective antibiotic therapy, CSF turns sterile within 24 hours and clinical response is obvious within 48-72 hours. Repeat CSF analysis is not necessary, indicated only in non-responsive cases after 48 hours.

Antibiotics should be continued IV for minimum 10-14 days (except in meningococci for 7 days and gram-negative meningitis for 21 days) or till the patient is afebrile for minimum 3-5 days.

II. Supportive therapy in BM includes:

• Continuous monitoring and management of hypo­tension, shock and respiratory problems.

• Parenteral fluid therapy to correct fluid/electrolyte imbalance and provide nutrition. Only 2/ 3^rd of calcu­lated fluid requirement should be given, as SIADH is present in 60-70% cases.

High-risk cases: Head injury, neurosurgery, CSF-Shunt

TGC: 3rd generation cephalosporins, e.g. ceftriaxone, cefotaxime or ceftazidime

Antibiotic doses in meningitis are usually higher than those for other indications, as follows:

Ampicillin (200-400 mg/kg/d), Amikacin (15 mg/kg/d), Gentamycin (6-8 mg/kg/d), Penicillin (3,00,000 IU/kg/d), Vancomycin (60 mg/ kg/d), Ceftriaxone (100 mg/kg/d), Cefotaxime (200 mg/kg/d), Ceftazidime (150-200 mg/kg/d), Cefepime (50 mg/kg/d)

All drugs are given IV; and in 3 divided doses, except penicillin (in 4-6 divided doses)

• Treatment of raised ICP with IV 3% hypertonic saline or mannitol (Ch 18.4).

• Treatment of seizures with IV Midazolam (0.2 mg/kg), followed by long-term anticonvulsants, e.g. phenytoin or phenobarbitone. Prophylactic anticonvulsants, even in absence of seizures, are indicated during acute phase of BM.

• Steroids, e.g. Dexamethasone (0.15 mg/kg/dose 6-hourly 2-3 days) may be useful to reduce cerebral edema and inflammation as well as to improve anti­biotic penetration. While exact role of steroids in BM is controversial, available evidence support their value in cases with focal signs to reduce the risk of complications, e.g. hearing loss or hydrocephalus. However, steroids may be useful only if given within first 4 hours of antibiotic therapy.

• General nursing care to prevent aspiration, bed sores and bladder/bowel retention along with symptomatic treatment for fever, etc.

• Treatment of complications, e.g. hydrocephalus, sub­dural effusion or ventriculitis, which are likely in non-responding cases and needs to be excluded by neuroimaging.

Subdural empyema is common in H. influenzae meningitis and may need neurosurgical intervention with repeated tapping or burr-hole drainage, with longer course of antibiotics for 4-6 weeks.

Ventriculitis may need repeated ventricular tapping, preferably after placement of Ommaya reservoir, with or without intraventricular instillation of antibiotics. Shunt placement is rarely required. Ifnecessary, shunt surgery in BM should be deferred till CSF is abnormal, due to risk of shunt block and infection.

Outcome: With early and appropriate antimicrobial therapy, mortality in BM is lt;10%, though 10-20% of recovered cases may develop neurodevelopmental sequelae, e.g. (i) intellectual disability or learning dis­abilities, (ii) secondary epilepsy, (iii) focal motor deficits, and (iv) hearing, visual or speech impairment. Hydrocephalus is uncommon in BM.

Sensorineural hearing loss is the commonest sequelae of BM, specially in cases with—(a) age lt;6 months, (b) peumococcal meningitis, (c) high CSF bacterial count, (d) persistent seizures/coma despite 72-96 hours of antibiotics.

Repeated episodes of BM may be due to—(a) recru­descence, i.e. resurgence of infection during therapy due to secondary drug resistance, (b) relapse after 3-21 days of completed therapy due to persistent focus, e.g. ventriculitis, subdural empyema or cerebral abscess and (c) recurrence due to anatomical/immunological defects. Prevention of BM involves—(a) routine vaccination against Hib and PCV, (b) vaccination for meningococci in high-risk children, and (c) rifampicin prophylaxis in contact of meningococcal carriers/contacts (Ch 10.10).

18.12.2