Meningitis

where is CSF produced?

in the lateral ventricles

where does CSF travel?

through the cerebral aqueduct and ventricles to the surface o the brain and down the spinal cord

how can you increase BBB permeability/penetration of drug into the CSF?

inflammation of meninges, decreased MW, unionized, increased lipid solubility, decreased plasma protein binding

what are the three pathways of meningitis

hematogenous from another infection site, contiguous from sinus, mastoid, or osteomyelitis, direct from trauma, surgery, etc.

risk factors for bacterial meningitis

head trauma, age (young and elderly), alcoholism, DM, smoking, immunosuppression (high-dose steroids, HIV/AIDS, immunoglobulin deficiency, splenectomy history, organ transplant), previous infection/colonization, crowding dorm/residential life

what is the classic triad of meningitis

fever, neck stiffness, and altered mental state

what are some signs and symptoms of meningitis

fever, neck stiffness, altered mental status, HA, confusion, seizures, Kernig’s or Brudzinski’s signs

what is Kernig’s sign

inability to straighten the leg when the hip is flexed to 90 degress

what is Brudzinski’s sign?

flexion of the neck causes hip and knee flexion - patients often experience pain

diagnostic approaches for meningitis

lumbar puncture (LP), blood cultures, or computer tomography of the head (CT head)

what occurs in lumbar puncture

done beside with sterile field - CSF culture and gram stain

when is CT of the head used for meningitis diagnosis

high risk populations to rule out intracranial lesions (brain herniation with LP), can be ± MRI

CSF interpretations for bacterial meningitis

20-50 cm H20 opening pressure, clear/cloudy/purulent CSF appearance, 1000-5000 WBC count, neutrophils are predominant WBC, glucose < 40 mg/dL (bacteria chowing down), CSF : serum glucose of </= 0.4, and 100-500 mg/dL of protein

CSF interpretations for viral meningitis

5-18 cm H20 opening pressure, clear CSF appearance, 10-1000 WBC count, lymphocytes (neutrophils early) are predominant WBC, glucose 40-85 mg/dL, CSF : serum glucose of >/= 0.6, and protein 50-100 mg/dL

bacterial meningitis pathogens

gram positives (S. pneumonia, L. monocytogenes), gram negatives (H. influenza, N. meningitides, enterobacteriacae)

viral meningitis pathogens

enteroviruses (ECHO, coxsachie, ppoliomyelitis), mumps, varicella zoster, EBV

fungal meningitis pathogens

cryptococcus, coccidioidomycosis, histoplasmosis, coccidioidomycosis

which antibiotics have poor therapeutic levels for BBB penetration

1st and 2nd gen cephalosporins, aminoglycosides, amphotericin, and clindamycin

which antibiotics have therapeutic levels for BBB penetration with inflammation

ampicillin, ceftriaxone, vancomycin, FQs, carbapenems, daptomycin, penicillin’s, aztreonam

which antibiotics have therapeutic levels for BBB penetration with or without inflammation

linezolid, FQs, metronidazole TMP/SMX, -azoles, acyclovir

empiric treatment for < 1 month old neonates with strep agalactiae, gram genative enterics, or L. monocytogenes

ampicillin (for listeria coverage) + cefotaxime or genatmicin

empiric treatment for ages 1-23 months with strep agalactiae, s. pneumoniae, N. meningitidis, or H. influenzae

ceftriaxone or cefotaxime + vancomycin

empiric treatment for 24 months - 50 years old with strep pneumoniae or N. meningitidis

ceftriaxone or cefotaxime + vancomycin

empiric treatment for > 50 years old with S. pneumoniae, N. meningitidis, gram negative enterics, or L. monocytogenes

ampicillin (for listeria coverage) + cefotaxime or ceftriaxone + vancomycin

what is the preferred monitoring for severe MRSA infections (eg. infective endocarditis, bactermia, osteomyelitis, meningitis, sepsis, and penumonia)

AUC

which pathogen is the leading cause of meningitis in patiets > 1 month old in the US?

streptococcus pneumoniae

where does streptococcus pneumoniae typically originate from

ears or sinuses

T/F: S. pneumoniae has a high rate of neurological complications such as coma, hearing loss, and seizures

true

recommended/standard antibiotics for S. pneumoniae meningitis if penicillin MIC is 0.1 μg/mL

penicillin G or ampicillin

recommended/standard antibiotics for S. pneumoniae meningitis if penicillin MIC is 0.1-1.0 μg/mL

3rd gen cephalosporin

recommended/standard antibiotics for S. pneumoniae meningitis if penicillin MIC is >/= 2 μg/mL (or ceftriaxone MIC >/= 1.0 μg/mL)

vancomycin + 3rd gen cephalosporin

alternative antibiotics fofr S. pneumoniae meningitis

3rd gen cephalosporin, cefepime, meropenem, fluoroquinolone

duration of therapy for S. pneumoniae meningitis

10-14 days

what patient population does Neisseria meningitidis predominate in?

patients > 1 month old

how is Neisseria meningitidis spread?

respiratory droplets (daycare, schools, military)

what can patients with Neisseria meningitidis present with?

petechiae

standard antibiotics for Neisseria meningitidis with a penicillin MIC <0.1 μg/mL

penicillin G or ampicillin

standard antibiotics for Neisseria meningitidis with a penicillin MIC 0.1-1.0 μg/mL

3rd gen cephalosporin

alternative antibiotics for Neisseria meningitidis with a penicillin MIC <0.1 μg/mL

3rd gen cephalosporin, chloramphenicol

alternative antibiotics for Neisseria meningitidis with a penicillin MIC 0.1-1.0 μg/mL

chloramphenicol, FQ, meropenem

duration of therapy for Neisseria meningitidis

10-14 days

standard therapy for b-lactamase positive H. influenzae

ampicillin

standard therapy for b-lactamase negative H. influenzae

3rd gen cephalosporin

alternative therapy for b-lactamase positive H. influenzae

3rd gen cephalosporin, cefepime, FQ

alternative therapy for b-lactamase negative H. influenzae

cefepime, FQ

duration of therapy for H. influenzae

7 days

standard therapy for L. monocytogenes

ampicillin or penicillin G

alternative therapies for L. monocytogenes

TMP/SMX, meropenem

duration of therapy for L. monocytogenes

>/= 21 days

standard therapy for enterobacteriaceae

3rd gen cephalosporin

alternative therapy for enterbacteriaceae

aztreonam, FQ, meropenem, TMP/SMX, ampicillin

duration of treatment for enterobacteriazeae

21 days

what is considered aseptic meningitis

viral meningitis

what mainly causes viral meningitis

enteroviruses

what has a 70% mortality rate in encephalitis

herpesviruses (HSV-type I and II)

when should antiviral coverage be given?

severely ill, significantly altered mental status, HSV history

what should be given for treatment of viral meningitis

acyclovir 10 mg/kg IV piggyback Q8H and ensure proper hydration

why is dexamethasone used in some cases of meningitis?

reduces inflammatory cytokines (TNF and IL-1) - some studies show no change while others show decrease mortality and decreased neurologic sequelae

dexamethasone treatment recommendation for infants and children with H. influenzae meningitis

0.15 mg/kg every 6 hours for 2-4 days administered before 1st antibiotic dose

dexamethasone treatment recommendation for adults with pneumococcal meningitis

0.15 mg/kg (max 10 mg) every 6 hours for 2-4 days administered before 1st antibiotic dose

what complications can occur when meningeal invasion occurs?

increased intracranial pressure, cerebral vasculitis and metabolic disturbances (cerebral ischemia, herniation, and possibly death)