Acute Bacterial Meningitis Beyond the Neonatal Period

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 à 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 PREVENTION. Vaccination and antibiotic prophylaxis Compiled by Dr.N.S.Mani