Meningitis

Presented ByAfshin Shiva, Pharm.D.

PGY2 Resident of clinical Pharmacy

Famous People Whose Lives Were Touched by Meningitis

Francisco Goya (C18 painter) became deaf at age 47 possibly due to meningitis. Source: PubMed

Mark Twain (American humourist and author) had a daughter Suzy who died in 1896 while Twain was in England. Source: The Mark Twain House & Museum

Spice Girl Victoria "Posh Spice" Beckham had viral meningitis in 2000. Source: BBC News

Objectives

• Define meningitis

• Describe prevalence

• Explain pathophysiology

• Identify Clinical Manifestations

• Define Appropriate Treatment

• Describe Methods of Prevention

What is meningitis?……

The brain and spinal cord are covered by 3 connective tissue layers collectively called the meninges which form the blood-brain barrier.

-the pia mater (closest to the CNS)

-the arachnoid mater

-the dura mater (farthest from the CNS).

The meninges contain cerebrospinal fluid (CSF).

Meningitis is an inflammation of the

meninges, which, if severe, may become

encephalitis, an inflammation of the brain.

Anatomy• Meninge: shock absorber

Dura mater

Arachnoid

Pia mater

Epidural

Subdural

LeptomeningeSubarachnoid

Meningitis……

Definition    Meningitis is an infection which causes inflammation of the membranes covering the brain and spinal cord.

Non-bacterial meningitis is often referred to as ‘aseptic meningitis’ – eg. viral meningitis Bacterial meningitis may be referred to as ‘purulent meningitis’.

Causes and risksThe most common causes of meningitis are viral infections that usually resolve without treatment. Bacterial infections of the meninges are extremely serious illnesses, and may result in death or brain damage even if treated.

For bacterial meningitis, it is also important to know which type of bacteria is causing the meningitis because antibiotics can prevent some types from spreading and infecting other people.

Caused by virus. Less severe Resolves without specific treatment within a week or two Also called as aseptic meningitis Eg : Enteroviruses

Caused by bacteria Quite severe and may result in a) brain damage b) hearing loss c) learning disability It would also causes death!

Microbiology

• Neonates (infants <1 months):

Most caused: Streptococus B (Agalactiie, )

Coliform (E-coli) Listeria monocytogenesis

Acquired: birth canalHospital invirontment

Case fatality rates:group B streptococci: >20% gram-negative bacilli: 30%

Microbiology• Infants:

Caused by:

Haemophilus influenzae

Streptococcus pneumoniae

Neisseria meningitidis.

Up to 45% of all cases before 1985 were by H. influenzae type b (Hib).From 1987 through 1997, however, Hib meningitis cases in children <5 years of age decreased by 97%.

most cases now are observed in adults.

Microbiology

• Adults and children:

most often is caused by :S. pneumoniae (the pneumococcus)

N. meningitidis (the meningococcus)

Meningococci common: 5 to 30 y pneumococci predominant: >30 y

Traditionally susceptible to penicillin, Pneumococcal strains showing penicillin resistance

In the past several years, meningococcal meningitis has been occurring in clusters within the general population with increased frequency.

Microbiology

• The elderly :

most susceptible:

S. pneumoniae (the pneumococcus)

N. meningitidis (the meningococcus)

Enteric gram-negative bacilli (e.g., E. coli, Klebsiella pneumoniae)

L. Monocytogenes

Mortality: higher than in other age groups

Prevalence

• 1806: 1st epidemic in America – Medfield MA• Incidence

2.5 to 3.5 cases per 100,000 people 0.16 to 0.45 per 1,000 live births Approximately 1.2 million cases of bacterial meningitis occur

annually worldwide

Common Organisms: 1986 - H. influenzae (45%), S. pneumoniae (18%), N.

meningitidis (14%) 1995 - S. pneumoniae (47%), N. meningitidis (25%), Listeria monocytogenes (8%), H.influenzae (7%)

Pathophysiology

• Hematogenous spread (most common)– blood to subarachnoid space

• Mechanical disruption– Fracture of the base of the skull– Direct extension from ear, mastoid air cells,

sinuses, orbit or other adjacent structure

19

Pathogenic Event 

Host Defense Bacterial Evasion Mechanism

Colonization andmucosal invasion, 

1. Secretory IgA  2. Cellular cilia activity 3. Mucosal epithelium

IgA protease secretion Ciliostasis Adhesive pili

Survival in the blood stream

Activation of Complement Pathways

Blockage of Alternative Compliment Pathway by Mechanisms on the cell surface

Crossing the blood-brainbarrier

Cerebral endothelium Passage through tight junctions between cells, mechanism unknown

Survival within the CSF Poor opsonic activity Rapid bacterial replication 

Symptoms and Signs in Patients with Bacterial Meningitis

Headache 90%

Fever 90%Stiff neck (Nuchal rigidity) 85%Altered mental status 80%Kernig’s or Brudzinski’s sign 50%Seizures 30%

Other: – N&V (35%), photophobia, papilledma, irritability, diffuse rash,

petechia, purpura

Laboratory Data

• Blood Tests:– CBC with diff– Blood culture– Coags if any petechiae or purpura noted

• CSF:– Cell Count– Glucose and protein– Gram stain– Culture and sensitivity

CSF• Origin :(Choroid Plexus in I,II Ventricle), unilateral, 550ml/d

Adult=150ml

Volume Infant=60-100 ml (5 mg Gentamycin :Adult = 33mcg/ml)

Neonate=40-60ml

PH = 7.3

Lytes = <serum

Pr. = <50mg/dl

Glu. = 60% plasmaWBC = <5 cell/mm3

CSF Findings

Microbial Etiology

WBC Count

(cells/mm3)

Predominant Cell

Type Protein GlucoseBacterial >500 PMN Elevated –

Fungal 10–500 MN Elevated Variable

Viral 10–200 PMN or MN

Variable Normal

Diagnosis

• Clinical features

• CT scan may show no evidence of a mass

• Cloudy spinal fluid with increased numbers of white

cells, high protein and low glucose

• Organisms seen on gram stain (may be negative

when antibiotics have been administered)

• CSF culture

• Throat and stool culture for suspected viral meningitis

Treatment: General Principle

• Avoidance of delay• Emperical antibiotic

Treatment Considerations

• Allergies• CSF Penetration• Empiric Therapy: Age specific• Dosing• Cultures/Sensitivities• Pathogen Specific Therapy• Duration of Therapy

CSF Penetration

• Lipophilicity:

Chloramphenicol

• Protein binding :

Ceftriaxone

• Molecular size:

Vancomycin

Empiric Therapy: Age specificAge Group or Predisposing

ConditionRecommended

Therapy Alternative TherapyNeonates (<1

mo)Ampicillin + cefotaxime Ampicillin +

gentamicinInfants and

children (1–23 mons)

Cefotaxime or ceftriaxone + vancomycin

Vancomycin + rifampin + aztreonam

Older children and adults (2–50

yr)

Cefotaxime or ceftriaxone + vancomycin

Vancomycin + rifampin + aztreonam

Elderly (>50 yr) Ampicillin, cefotaxime, or ceftriaxone + vancomycin

Vancomycin + TMP-SMX + aztreonam

Adjunctive Treatment• Dexamethasone: Controversial

Rationale: inflammatory cytokines have role in pathophysiology of bacterial meningitis

Debate: adjunctive therapy could reduce penetration of antibiotics into the CNS

Clinical trials show benefit: reduced audiologic and neurologic complications

Benefit seen only in patients infected with H. influenza Benefit seen in patients infected with S.pneumo but not statistically

significant

AAP recommends initiation 30 minutes prior to 1st dose of antibiotics

Dose: 0.15 mg/kg/dose IV q6h x 4 days

Optimization of Antibiotic Therapy

• Once culture information is available and organism has been identified, review antibiotic choices to ensure appropriate treatment

• Determine duration of therapy based on organism identified

Pathogen-Specific Therapy

Organism Duration

Neisseria meningitis 7-10 days

H. Influenzae 7-10 days

Streptococcus pneumoniae 10-14 days

Group B Streptococcus 14-21 days

Listeria monocytogenes 14-21 days

Other gram negative bacilli 21 days

AmpicillinSpectrum: Group B Strept, S. pneumo, Listeria, N.

meningitidis

• Class– Penicillin

• Dosing– 200 mg/kg/day IV Q6h – Max Dose = 12 g/day– Adjust in renal

impairment

• Contraindications– Hypersensitivity to

penicillin

• Adverse Events– Injection site pain – Rash– Diarrhea

– Nausea/vomiting

PenicillinSpectrum: S. aureus, N. meningitidis

• Class Penicillin

• Dosing 300,000 – 400,000

units/kg/day IV Q4-6h

Max Dose = 24 MU/day

• Contraindications Hypersensitivity to

penicillin

• Adverse Events Rash Diarrhea Nausea and

Vomiting

Cefotaxime (Claforan®) Spectrum: S. pneumo, N. meningitidis, H.influenzae, E.

coli

• Class Cephalosporin

• Dosing 200-300 mg/kg/day

IV Q6h Max Dose = 12

g/day

• Contraindications Hypersensitivity to

cephalosporins

• Adverse Events Rash, Pruritus Diarrhea, colitis Injection site pain Nausea/vomiting

Ceftriaxone (Rocephin®)Spectrum: S.pneumo, N.meningitidis, H.influenzae, E.

coli

• Class Cephalosporin

• Dosing 75 - 100 mg/kg/day IV

q12h-QDay Max Dose = 4 g/day

• Contraindications Hypersensitivity to

cephalosporins

• Adverse Events Rash Diarrhea, Injections site pain Increased LFT’s

Vancomycin (Vancocin®)Spectrum: S.aureus, S.pneumoniae

• Class– Glycopeptide

• Dosing– 60 mg/kg/day IV q8h – No max dose but some

references suggest 4g– Check trough levels to

determine appropriate dosing

• Trough should be > 5 mcg/mL

• Contraindications– Hypersensitivity to

Vancomycin – If red man’s may slow infusion and adm over 2hrs

• Adverse Events– Flushing– Redman’s syndrome,– Neutropenia– Vasculitis – Nephrotoxicity/Ototoxicity

Complications of MeningitisComplications of Meningitis

• Young children:

1. Babyish behavior2. Forgetting recently

learned skills3. Reverting to bed-wetting

One of the most common problems resulting from meningitis is hearing loss. Anyone who has had meningitis should take a hearing test.

• Older people:1. Lethargy 2. Recurring headaches 3. Difficulty in

concentration 4. Short-term memory

loss 5. Clumsiness 6. Balance problems 7. Depression

Serious complicationsSerious complications

• Other serious complications can include:

1. Brain damage

1. Epilepsy

2. Changes in eye sight

Prevention

• N. meningitidis Prophylaxis of close contacts

• Rifampin • < 1 month old: 10 mg/kg q24h x2 doses • > 1 month old: 20 mg/kg q24h x 2 doses • Adults: 600 mg q12h x 4 doses

• Ceftriaxone 150 ,250 mg IM x 1 dose• Ciprofloxacin 500 mg x 1 dose

• Immunizations Pneumococcal Vaccine for children < 2 yrs Meningococcal Vaccine for all 11-12 year olds,

unvaccinated adolsecents at high school entry, all college freshmen living in dormitories, and ≥ 2 years at high risk

Hib Vaccination

for children > 2 monthso HbOC: Polyribosylribitol(PRP)+ diphthria toxin protein.o PRP-T: PRP + tetanus toxino PRP-OMP: PRP + Outer memberane complex protein of N.meningits

ScheduleVaccine (Trade

Name) 2 Months 4 Months 6 Months 12 Months 15 Months

HbOC (HibTITER)Dose 1 Dose 2 Dose 3

—Booster

PRP-T (ActHIB) Dose 1 Dose 2 Dose 3 — Booster

PRP-OMP (PedvaxHIB)

Dose 1 Dose 2 — Booster —

Mortality Meningitis

Community Acquired

Gram-negative

1962-1970 24% 21%

1971-1979 26% 34%

1980-1986 24% 13%

Nosocomial 35%

Risk Factors Relative RiskAge > 60 2.1Obtunded Mental Status 3.0Seizures 4.0