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Published by Ira Moh ッ
A document about Meningitis, its causes and cures.
A document about Meningitis, its causes and cures.

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Published by: Ira Moh ッ on Apr 07, 2011
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Central Nervous System infections

CNS infections
Refers to a variety of infections involving brain, spinal chord & associated tissues, fluids & membranes.

CNS protection
A. from internal/external change;
1. Biochemical insults by BBB 2. Physical insults by Skull, vertebrae, and meninges

1. 2. 3. Formation by choroid plexus Composition Drainage from arachnoid villi

WBCs;< 5/mm3 Diff WBCs; monocytes Protein Glucose -ve gram stain

Subarachnoid space

The Brain

Definitions of CNS Infections  

Meningitis: Inflammation of membranes of brain & spinal chord (meninges) & CSF in contact with these membranes Encephalitis: An inflammation of the brain itself.

Epidemiology of Infectious Meningitis 

Primarily a pediatric disease, also elderly Over 95% mortality without treatment, up to 25% with treatment 10% of survivors develop neurologic complications: 

Seizures, hydrocephalus, deafness, blindness, paralysis, hemi paresis, mental retardation, learning disability - due to cerebral edema and vasculitis; deafness due to spread of bacteria to cochlear apparatus early in infection

Etiology of Infectious Meningitis  


Causes; bacterial, fungal, T.B, viral & spirochetes Bacterial meningitis is most common Vaccination has reduced incidence & caused a shift of age distribution from very young to older individuals Prior to empiric Abx initiation; estimate individual patients¶ risk factors

Risk factors for CNS infections 

Environmental (recent exposure); close
contact with someone having meningitis, RTI 

Recent infection in patient; RT, OM, sinusitis,

Immunosuppresion; HIV, cancer, cirrhosis,

Surgery, trauma, neurosurgery, CSF shunt.


Source of infection

‡Contiguous spread; sinusitis, OM, birth defects ‡ Hematogenous; bacteremia seeding meninges ‡ Direct inoculation; trauma, neurosurgery complicate ‡ Reactivation of Latent disease; HSV, T.B

Entry into CNS

Cerebral edema; Inc. ICP, Dec. CBF

S&S of meningitis

If uncontrolled; pathophysiologic changes lead to cerebral ischemia & death

Pathophysiology of Acute Bacterial Meningitis 

Organisms: S. pneumoniae, N. meningitidis, Listeria monocytogenes, H. influenzae (Hib) Nasopharyngeal colonization with phagocytosis across cells into the bloodstream Bacterial polysaccharide capsule resists phagocytosis by neutrophils Persistent, dense bacteremia permits invasion of subarachnoid space Inadequate host defense mechanisms within the CSF Bacterial cell wall components cytokine release inc. BBB permeability, V.D, cerebral edema, o ICP, ischemia, death


History and Physical Examination 

History; risk factors for infection & recent exposures Adult Signs/Symptoms: Headache, fever, stiff neck or back, nausea, altered mental status, photophobia; later confusion, seizures, coma Infants: Irritability, high-pitched crying, altered sleep, vomiting, poor feeding, seizures, rash Physical Exam: (+) Kernig's Sign, (+) Brudzinski Sign; reflexes that indicate irritation of nerve tracts in spinal column Accompanying sepsis: low blood pressure, rapid heart rate, poor peripheral perfusion Shock ± common with Neisseria meningitidis Evidence of septic emboli: petechiae (N. meningitidis)

Kernig s Sign


Flex hip to 90o toward trunk. Attempt to extend knees. Positive if spasm at knee when extended to 135o.

Brudzinski s Neck Sign

Flexion of the neck produces hip and knee flexion.

Laboratory Evaluation  

CSF from Lumbar Puncture (Caution; Contraindications)
Contraindications: Cardio respiratory insufficiency, increased intracranial pressure, CNS mass, Brain Herniation, Bleeding, Seizures, Unconsciousness, Focal neurologic sign.  


leucocytosis: WBC count 400-10,000 cells/mm3; > 95% neutrophils in bacterial meningitis Low CSF glucose < 50% of blood glucose) Elevated CSF protein (> 50 mg/dL) Gram stain and culture of the CSF

Management algorithm for adults with suspected bacterial meningitis

CSF findings in different infections

CSF findings in different infections

Goals of Treatment 

Eradicate infection Relieve signs and symptoms Prevent neurologic complications (e.g., seizures, deafness, coma, death) measures for future prevention (e.g. vaccines & suppressive therapy)

Principles of Antimicrobial Therapy for Meningitis     

High dose Parentral IV therapy is mandatory; high levels reached to sterilize CSF Immediate empiric therapy with broad-spectrum agents based on age & risk factors until causative organism identified Once organisms identified (2-3 days), tailor the regimen to the specific pathogen; Definitive treatment During treatment, monitor signs/symptoms, CSF cultures and physical examination Continue treatment for 7 to 14 days or longer; depending on organism If steroids are used; administer prior to or at same time w Abx

Principles of Antimicrobial Therapy for Meningitis  

Antimicrobial PK & Pdynamics; low-mol wt lipophilic Abx that are un-ionized at physiologic pH & not highly PPB penetrate best in CSF & other body tissues, fluids Integrity of BBB determines Abx penetration into CSF CSF penetration of most, but not all, Abx is enhanced by presence of infection & inflammation

Principles of Antimicrobial Therapy for Meningitis   

Sulfonamides, trimethoprim, chloramphenicol,rifampin; achieve therapeutic CSF levels even without meningeal inflammation - lactams & monobactams, vancomycin, quinolones, acyclovir, linezolid, & colistin; therapeutic CSF levels with meningeal inflammation Amino-glycosides, 1st gen cephalosporins, 2nd gen(except cefuroxime), clindamycin, & amphotericin; do not achieve therapeutic CSF levels, even with inflammation (clindamycin achieves therapeutic brain tissue levels)

Empirical Antimicrobial Therapy for Meningitis  



Empirical therapy should be directed at the most likely pathogen(s) for a specific patient, taking into account; Age risk factors for infection (underlying disease, immune dysfunction, vaccine history & recent exposures) CSF Gram stain results CSF antibiotic penetration Local antimicrobial resistance patterns (Refer to Table; 67-1 , P. 1035; Ch 67) After CSF culture is available; narrow empirical therapy for definitive organism In absence of a positive Gram stain, empirical therapy should be continued for at least 48 -72 hours

Management of Meningitis Caused by Specific Organisms
1. 2. 3. 4. 5. 6.

Neisseria meningitidis Streptococcus pneumoniae Haemophilus influenzae Enteric gram negative Listeria monocytogenes Herpes simplex virus

Neisseria Meningitidis: A Gram-Negative Diplococcus

Neisseria Meningitidis (Meningococcus) 


20% of all cases, 60% in ages 2-18 years Common in children, young adults Usually transferred by an asymptomatic or infected nasal carrier Most cases in winter or spring Often occurs in clusters (e.g., schools) 11-19 % of survivors experience long term sequelae; hearing loss, limb loss & neurologic deficits Fatality rate 3% if treated appropriately

Signs and Symptoms of N. Meningitidis Meningitis 

50% have petechiae and/or purpura Seizures, coma are common May be aggressive behavior 10% deafness in one or both ears; usually permanent if cochlear nerve damage Pts w fulminant meningococcal sepsis; shock, DIC & MODS; poor prognosis & 80% mortality Immune reaction of fever, arthritis 10-14 days after onset, despite treatment Suspected pts shd be kept on respiratory isolator 1st 24 hrs of ttt

Treatment of N. Meningitidis
Penicillin MIC 0.1 mg/L 

Penicillin MIC; 0.1-1mg/dL 

First Choice: 

First Choice: 

Ceftriaxone OR cefotaxime Moxifloxacin 400mg IV Q 24 hrs OR Meropenem 2g IV Q 8 hrs OR; Chloramphenicol 1-1.5 g IV Q 6 hrs 

High-dose penicillin G 4 million unit IV Q 4 hrs OR; Ampicillin 2g IV Q 4 hrs Ceftriaxone 2g IV 12 hrs OR Cefotaxime 2g IV Q 4 hrs 



Duration; 7 days

Treatment of N. Meningitidis
Prophylaxis of close contacts: Close contacts have a 400-800 times increased risk for meningitis Prophylaxis started ASAP w in 24 hrs, after 14 days; less benefit
‡ Adults: Rifampin 600 mg Q 12 hrs (2days) OR; ciprofloxacin 500 mg PO (once) OR: ceftriaxone 250mg IM (once) ‡ Children >1 mo: 10 mg/kg Q 12 hours (2days) ‡ Infants <1 mo: 5 mg/kg Q12 hours (2 days) ‡ < 12 yrs: ceftriaxone 125 mg IV (once)

Petechiae associated with N. meningitidis

Streptococcus Pneumoniae: Gram-Positive Cocci

Pneumococcal Meningitis

Streptococcus Pneumonia (Pneumococcus)  


Very common cause of meningitis in adults & children < 2 years of age Also common in infants and younger children High risk; elderly, alcoholics, splenectomized, cocchlear implants 50% of cases are secondary infections resulting from nearby infections (ear, paranasal sinuses) Seizures and coma are common complications Overall fatality rate 20- 30%

Duration; 10 -14 days

Treatment of S. Pneumoniae
Pen MIC 0.1 mg/L
1st line; Penicillin G or ampicillin Alternative Therapies Ceftriaxone or cefotaxime or chloramphenicol

Pen MIC 0.1-1 mg/L
1st line; Ceftriaxone or cefotaxime Alternative Therapies Cefepime 2 g IV every 8 hours or meropenem

Penicillin MIC 2 mg/L or >;
1st line; Vancomycin 15 mg/kg IV Q 8 12 hrs + ceftriaxone or cefotaxime Alternative Therapies Moxifloxacin

Cefotaxime/ceftriaxone MIC at least 1 mg/L
1st line; Vancomycin + ceftriaxone or cefotaxime Alternative Therapies Moxifloxacin

Haemophilus Influenzae: Gram-Negative Coccobacillus

Haemophilus Influenzae  



Effective vaccination against type b has reduced meningitis by 99% (children < 5 yrs in the U.S.) Now causes only 7% of meningitis cases May result from primary infection in middle ear or paranasal sinuses Case fatality rate 6% 30% to 40% of strains are resistant to ampicillin Hib vaccine recommended for pts undergoing splenectomy

Duration; 7 days

Treatment of H. Influenzae  

-lactamase positive:  First Choice: Cefotaxime or ceftriaxone  Active whether resistant or not  Little toxicity  Serum concentration monitoring not required  Alternative; Cefipime or Moxifloxacin or Chloramphenicol -lactamase negative:  First Choice: Ampicillin 200-400 mg/kg/day in 4 doses  Alternative: Cefotaxime or ceftriaxone or Cefipime or Moxifloxacin or Chloramphenicol

Treatment of H. Influenzae 

Close contacts; 

Risk of Hib meningitis in close contacts is 200-1000 times normal Rifampin (600 mg/day for adults; 20 mg/kg per day for children, maximum of 600 mg/day) is administered for 4 days. Rifampin prophylaxis is not necessary for individuals who have received the full Hib vaccine series Exposed, unvaccinated children between 12 and 48 months of age should receive one dose of vaccine unvaccinated children 2 to 11 months of age should receive three doses of vaccine, as well as rifampin prophylaxis.    

Enteric Gram-negative Meningitis
Escherichia coli

Pseudomonas aeruginosa

Klebsiella pneumoniae

Enteric Gram-negative Meningitis 


The fourth leading cause of meningitis Increased risk in neonates, elderly Optimal therapy not fully defined Antipseudomonal penicillins and aminoglycosides penetrate CSF poorly Direct intraventricular administration of aminoglycoside may be necessary Continue IV therapy for 21 days Pts at risk; DM, immunosuppresed, elderly, malignancy, w CNS defects Local therapy (intrathecal or intraventricular therapy) for; pts w G-ve bacillary meningitis (esp MDR P. aeruginosa) or in pts who fail to improve on IV Abx alone

Duration; 21 days or more

Treatment of Enteric Gram(-ve) Meningitis
Pseudomonas aeruginosa: st line; Cefipime or Ceftazidime 2g IV Q 8hrs or 1 meropenem + aminoglycoside  Alternative; Aztreonam or Ciprofloxacin 400mg IV Q 812 hrs +/- Aminoglycosides E. coli & Klebsiella pneumoniae(Enterobacteriace st  1 line; Ceftriaxone or cefotaxime  Alternative Therapies; Aztreonam 2 g IV Q 6 8 hrs, Moxifloxacin or meropenem or TMP-SMX or ampicillin

Listeria Monocytogenes

Listeria Monocytogenes   


An intracellular G+ve organism that contaminates certain foods (e.g., raw fish,beef, poultry, vegetables, soft cheese, unpasteurized milk); when ingested organisms colonize GIT & if overcome immune response; penetrate the intestinal lumen & enter blood stream Causes 8% of meningitis cases Affects neonates, elderly, alcoholics, immunocompromised patients Prophylaxis for close contacts is not required

Duration; 26 days

Treatment of Listeria Meningitis 

First 10 days: Combination therapy with: 

Ampicillin 200-400 mg/kg/day in 4 doses + gentamicin IV Penicillin G Ampicillin Trimethoprim-sulfamethoxazole 

Finish with monotherapy: 

Treat for 2 to 3 weeks after improvement seen to prevent relapse

Adjunctive Dexamethasone Therapy for Meningitis 

Used to reduce neurologic complications (e.g., hearing loss) in pediatric patients Inhibits production of inflammatory mediators tumor necrosis factor (TNF) & interleukin-1 (IL-1) Dose: 0.15 mg/kg IV Q 6 hrs for 2-4 days or 0.4 mg/kg every 12 hours for 2 days Use in children with H. influenzae meningitis Consider if • 2 months old or adults with pneumococcal meningitis 

Initiated 10-20 min prior to Abx adm ( no benefit if administered post Abx adm)

Adjunctive Dexamethasone Therapy for Meningitis 

Caution w administration of dexamethasone with vancomycin
(patients w pneumococcal meningitis caused by penicillin- or cephalosporinresistant strains);   

Animal models; concurrent steroid use reduces vancomycin penetration into the CSF by 42% to 77% and delays CSF sterilization due to reduction in the inflammatory response. Treatment failures have been reported in adults with resistant pneumococcal meningitis who were treated with dexamethasone Animal models indicate a benefit of adding rifampin in patients with resistant pneumococcal meningitis whenever dexamethasone is used

Outcome Evaluation 


All pts w CNS infections shd be monitored continuously to assess efficacy & goal attainment During treatment monitor clinical S&S at least 3 times daily Fever, headache, N & V shd start to improve within 24-48 hrs from start of Abx Monitor CSF & bld cultures & tailor Abx Repeat cultures done to prove complete bacterial erradication Repeat LP indicated for pts who don t respond clinically after 48 hrs of appropriate Abx esp those w resistant pneumococcus who receive dexamethasone

Outcome Evaluation   

Other candidates for repeat LP include; those w infection w g (-ve) bacilli, prolonged fever & recurrent meningitis. In neonates to determine the duration of therapy performed to relieve elevated intracranial pressure Trough vancomycin conc of 15- 20 mg/L are recommended for the treatment of CNS infections. Monitor patients for drug adverse effects, drug allergies & drug interactions

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