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Bacterial Meningitis
- a life threatening emergency!
- direct correlation between survival and delay in antibiotic therapy
- Coma possible - with boar-like neck flexion
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Meningitis definition
- an acute purulent infection within the subarachnoid space. It is associated with a CNS inflammatory reaction that may result in decreased consciousness, seizures, raised intracranial pressure, and stroke
- The meneinges, the subarachnoid space, and the brain parenchyma are all involved in the inflammatory reactions
- meningoencephalitis: the more accurate descriptive term
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Epidemiology: bacterial meningitis
- Approximately 2.5 cases/100,000 population
- Receng change in epidemiology: H. influenza meningitis declined precipitously following the introduction of the H. influenza type b (Hib) vaccine in 1987, and H. influenza now accounts for <10% of bacterial meningitis cases
- Global emergence and increasing prevalence of penicillin- and cephalosporin-resistant strains of S. pneumonia
- For medium-resistant: can't just give more penicillin, need to give vancomycin
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Epidemiology: meningitis
- Annual meningitis epidemics: caused primarily by the serogroup A meningococcus, continue to occur in the meningitis belt of sub-Saharan Africa
- Epidemics due to the serogroup B meningococcus continue to occur in Europe, Latin America, and New Zealand
- Group B streptococcus or S. agalactiae: was previously responsible for meningitis predominantly in neonates, but it has been reported with increasing frequency in individuals >50 years, particularly those with underlying diseases
- Lysteria monocytogenes: has emerged as an important cause of bacterial meningitis in the elderly and in individuals with impaired cell-mediated immunity & pregnancy
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Meningitis in neonates
- within 72 hrs of birth
- E. coli
- Group B streptococcus
- Listeria monicytogenes - within 72 hrs but later
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Meningitis in infants less than 6 months
- E coli
- Group B Streptococcus
- Streprococcus pneumoniae
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Meningitis in Children from 6 months - 2 years
- Neisseria meningitis
- Streptococcus pneumoniae
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Meningitis in 2 yrs - 19 y.o.
- Neisseria meningitis
- Streptococcus pneumoniae
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Meningitis in > 60 y.o.
- Streptococcus pneumoniae
- Group B Streptococcus
- Listeria monocytogenes
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Major intracranial complications in bacterial meningitis in adults
- herniation
- infarction
- hydrocephalus
- seizures
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Pathophysiology of Meningitis
- Colonization of the nasopharynx
- Bacteria are transported across epithelial cells (and are encapsulated, so they avoid clearance)
- Bloodstream access
- Intraventricular choroid plexus
- Entry into CSF
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Pathophysiology: meningitis
- Bacteria rapidly multiply within CSG: decreased or absent WBC, complement and immunoglobulins; phagocytosis is impaired
- Many neurologic manifestations result from the inflammatory response: and not the bacteria. As a result, neurologic injury can progress even after the CSF has been sterilized by antibiotic therapy
- The lysis of bacteria: lipopolysaccharide (LPS); teichoic acid and peptidoglycans; Leukocytes
- Tumor necrosis factor and interleukin: (TNF) and (IL-1) appear in the CSF within 1 to 2 hrs of intracisternal inoculation of LPS
- Followed by an increase in CSF protein concentration and leukocytosis
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Pathogenesis of meningitis
- Cytokines and chemokines: TNF and IL-1 increase the permeability of the BBB
- exudate and proteins decrease the resorptive capacity of the arachnoid granulations leading to obstructive and communicating hydrocephalus
- Increased expression of selections: more leukocytes in CSF - adds to the inflammatory exhudate
- Neutrophil degranulation results in the release of toxic metabolites that contribute to cytotoxic edema, cell injury, and death
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(The cerebrovascular complications of bacterial meningitis)
- Narrowing of the large arteries at the base of the brain
- Infiltration of the arterial wall by inflammatory cells with intimal thickening (vasculitis)
- Thrombosis of the major cerebral venous sinuses, and thrombophlebitis of the cerebral cortical vein
- Combination of interstitial, vasogenic, and cytotoxic edema leads to raised ICP and coma
- Cerebral edema, either focal or generalized, can lead to cerebral herniation
- Focal or diffuse cerebral edema is the most likely cause of meningitis-associated brain herniation; however, hydrocephalus and dural sinus or cortical vein thrombosis may also play a role
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Clinical presentation of bacterial meningitis
- Fever
- Headache
- Altered mental status
- Stiff neck
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Symptoms of meningitis in elderly
- Fever: 59-100%
- Confusion: 57-96%
- Headache: 21-81%
- Nuchal rigidity 57-92%
- ** in elderly nuchal rigidity may always be present but will have resistance to rotation as well as flexion on exam
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Kernig Sign
- when patients sat on the edge of a bed with their legs dangling, an attempt to extend the knee joint more than 135 digress, or in severe cases more than 90 degrees, elicited spasm of the extremity that disappeared when the patient lay supine or stood up
- will cause pain in the posterior thigh
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Kernig maneuver today
- most commonly performed with the patient lying supine and the hips and knees flexed at 90 degrees
- a positive sign is present when extension of the knee from this position elicits resistance or pain in the lower back or posterior thigh
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Brudzinski sigh
- "nape of the neck" sign
- passive neck flexion in a supine patient results in flexion of the knees and hips
- a separate sign, the contralateral reflex, is present if passive flexion of one hip and knee causes flexion of the contralateral leg
- Are they sensitive, especially in the adult or elderly: absence in the elderly is not very sensitive
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Lumbar puncture: diagnosis
- Lumbar puncture is required
- These are risks to LP:
- herniation
- nerve injury
- bleeding
- infection
- ** the only way to rule in or rule out meningitis always analyze an LP!
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***When NOT to do LP
- unilateral findings on physical exam: asymmetry might have a mass which increases risk of herniation
- Papilledema: ICF throughout - can cause tonsillar herniation and compress the brainstem!!
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Spinal Fluid analysis: Bacterial Meningitis
- Low Glucose: generally less than 40 mg/dl or 0.5 CSF/serum ratio
- Elevated Protein: generally 100-500
- Neutrophilic pleocytosis: >100 wbc/hpf with >90% neutrophils
- Positive Gram Strain
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Spinal Fluid Formula: Bacterial
- General: Neutrophilic with low glucose and high protein
- Leukocytes: >100 mainly neutrophils
- Protein:100-500
- Glucose: <40 or <0.4 ratio
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Spinal Fluid Formula: Viral
- General:Lymphocytic (pleiocytosis); normal glucose slightly raised protein
- Leukocytes: 10-500
- Protein: slightly elevated
- Glucose: Normal
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Spinal Fluid Formula: Fungal
- General: Lymphocytic; lower glucose/raised protein
- Leukocytes: 50-500; mainly lymphocytes
- Protein: 50-150
- Glucose: Low
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Spinal Fluid Formula: TB
- General: Lymphocytic; with low glucose/high protein
- Leukocytes: 100-500; mainly lymphocytes
- Protein: 100-500; may be much higher
- Glucose: low and very low
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Differential Diagnosis for bacterial meningitis
- Bacterial meningitis
- Viral meningitis/encephalitis
- Fungal meningitis
- Brain abscess
- Parameningeal focus
- other
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Meningitis therapy for 16-50 years
- Neisseria meningitidis; Streptococcus pneumonoiae
- Tx: vancomycin plus a third-generation cephalosporin (ceftriaxone)
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Meningitis therapy for >50 yrs
- S. pneumoniae; N. Meningitis, Listeria monocytogenes, aerobic gram-negative bacilli
- Tx: Vancomycin plus a third-generation cephalicsporin PLUS ampicillin - for Lysteria
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What if you need a CT?
- treat with ABX prior to CT scan!!!
- Get blood cultures prior to ABX treatment!
- Additional studies on spinal fluid - can administer antibiotics even just before LP, because won't be sterilized right away
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Steroids use in meningitis in adults
- S. pneumonia: showed a significant reduction in mortality (w/S. pneumo)
- H.influenza b: decreases hearing loss
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Problems with steroid use in meningitis
- concentration of vancomycin in CSF is decreased by dexamethasone therapy
- Study did not have any cases of penicillin-resistant pneumococcus
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Delay in therapy after arrival in the emergency department
- was associated with adverse clinical outcome when the patient's condition advanced to the highest stage of prognostic severity before the initial antibiotic dose was given
- Increases morbidity and mortality!
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Prevention of meningitis
- Vaccine: for Nisseria meningitis
- Chemoprophylaxis
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Nisseria meningitis
Aerobic gram negative Coccus
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Meningeal pathogens
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitis
- Listeria monocytogenes
- E.coli and Group B streptococcus
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Neisseria meningitidis
- Causes sporadic disease in the U.S. (2400/year)
- Leading cause of meningitis in young adults
- High case-fatality ratio (50% untreated; 8-10% of treated)
- Epidemic killer world-wide associated with specific capsular polysaccharide types
- Epidemics occur every 8-14 years in the "meningitis belt" - in Africa - very large epidemic
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Meningococcal septicemia
- results when virulent organisms invade the blood stream
- ranges from low-level meningococcemia to fulminating sepsis
- high fever, arthralgia and small vessel blockage
- rash resulting from pinpoint hemorrhages (petechiae)
- in severe infections, dusky red blotches (purpura fulminans)
- hemorrhage and necrosis occur
- destruction of the adrenal glands: Waterhouse-Friedrichsen Syndrome
- - death can occur within 12 hours of onset
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Meningococcal meningitis
- begins suddenly with severe headache, high fever
- progressive stiffness o the neck, back and shoulders (positive Kernig's sign)
- photophobia may be present
- petechiae and purport are sometimes present
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Meningococcal Virulence Facors
- LOS
- Peptidoglycan fragments (PGF)
- Pili (Fimbriae)
- IgA protease - a secreted enzyme which cleaves human IgA (mucosal immunity)
- Polysaccharide capsule: an extracellular covering; blocks phagocytosis by macrophages and PMNs; important component for serotyping; Group B capsule is sialic acid
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Meningococcemia and Meningococcal Meningitis
- Medical emergency
- Treatment with ceftriaxone high dose or penicillin
- Increased incidence in terminal complement deficiency patients (C6-C9): may get recurrent meningococcal disease and their disease is less severe than community
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Nisseria meningitidis
- Vaccine
- new protein conjugated capsular vaccine with Group A, C, T and W135 polysaccharide (MCV4)
- Long-lasting immunity compared to the polysaccharide vaccine
- Initial concern with GBS, no association at present time
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Target patients for MCV4 vaccine
- College freshmen living in dormitories
- microbiologists who are routinely exposed to meningococcal bacteria
- U.S. military recruits
- Anyone traveling to, or living in, a part of the world where meningococcal disease is common, such as parts of Africa
- Anyone who has a damaged spleen, or whose spleen has been removed:
- anyone who has a terminal complement component deficiency (an immune system disorder)
- People who might have been exposed to meningitis during an outbreak - need chemoprophylaxis
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Listeria monocytogenes
- gram positive rod
- more frequently seen in immunocompromised patients
- high frequency of disseminated infections in pregnancy
- Seen in neonates, elderly, and immunocompromised
- Frequently causes a mingoencephalitis
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Listeria monocytogenes
- Gram positive rod
- microbiology: exhibits tumbling motility
- can be mistaken for a gram negative rod! - frequently happens
- Requires thorough pasteurization and the organism can multiply at 4C
- frequently associated with milk products
- consider in the T-cell immune deficiency, especially transplants and lymphomas; pregnancy associated; elderly and liver disease
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