1. Central Nervous System Infections, Swamy

OBJECTIVE: List the infecting pathogens in community-acquired bacterial meningitis

*streptococcus pneumoniae 2+ years

group b streptococcus (streptococcus agalactiae) *babies

neisseria meningitidis *2+ years

haemophilus influenzae type B *2+ years

listeria monocytogenes *50+ years

OBJECTIVE: List the infecting pathogens in healthcare-associated meningitis and ventriculitis

• CSF shunts

• CSF drains

• intrathecal infusion pumps

• deep brain stimulation hardware

• neurosurgery

• head trauma

OBJECTIVE: List the infecting pathogens in ventriculitis

OBJECTIVE: Identify risk factors for meningitis due to Listeria monocytogenes

• pregnancy

• infants less than 1 month

• adults over 50

• alcoholics with chronic liver disease

• immunocompromised

OBJECTIVE: Describe the pathogenesis of community-acquired bacterial meningitis

???

Hematogenous: spread via invasion into bloodstream and evasion of host defenses

Contiguous: infection at a place near CNS (nose or ear) that goes directly to the meninges

OBJECTIVE: Explain the principles of antimicrobial therapy in meningitis

• emergent idagnosis

• iV admin

• adequate CNS penetration

• aggressive dosing

• bactericidal agents

• appropriate spectrum of activity

OBJECTIVE: Design empiric antimicrobial regimens for patients with community- acquired bacterial meningitis based on age, predisposing conditions, and co-morbidities

OBJECTIVE: Define the sub-group of patients who will benefit from adjunctive dexamethasone in the setting of community-acquired bacterial meningitis

all organisms except S. pneumoniae

OBJECTIVE: Modify antimicrobial regimens for patients with community-acquired bacterial meningitis based on infecting pathogen and susceptibilities

OBJECTIVE: Design empiric antimicrobial regimens for patients with healthcare- associated meningitis and ventriculitis based on predisposing factors

OBJECTIVE: List the three most common infectious causes of encephalitis

1. Herpes Simplex Virus

   1. includes HSV1 (cold sores) > HSV2 (genital warts)

   2. sporadic → any time of the year

   3. treatable

2. Varicella Zoster Virus

   1. chickenpox/shingles

   2. more in immunocompromised

   3. treatable

3. West Nile Virus

   1. arbovirus (arthoropod borne - mosquito)

   2. more common in mosquito season (summer into fall)

4. Enteroviruses

   1. polioviruses, coxsackieviruses, echoviruses, etc

   2. transmitted via respiratory and fecal-oral

   3. summer and fall months

OBJECTIVE: Design empiric antimicrobial regimens for patients with suspected encephalitis

IV acyclovir → diagnostic studies to identify cause → continue for 14-21 days if HSV is confirmed

early treatment is very important

OBJECTIVE: Explain the pathogenesis of brain abscess

infection of brain tissue characterized by a well - vascularized capsule

early infection (1-2 weeks): acute inflammation

late infection (2-3 weeks): formation of necrotic pus → abscess

OBJECTIVE: List the infecting pathogens in brain abscesses based on the predisposing factor/source of infection

OBJECTIVE: Design empiric antimicrobial regimens for patients with brain abscesses based on the predisposing factor/source of infection

CNS Infections are located

within the cranium or spinal column (meningitis, ventriculitis, encephalitis, brain abscesses) and these are all medical emergencies

Anatomy of the Maters

SKULL

1. Dura Mater

2. Arachnoid Mater

   1. under here is the subarachnoid space where csf flows

3. Pia Mater

BRAIN

Role of brain tissue capillaries

used as a barrier due to its tight junctions and thick glial cells that keeps toxins and byproducts out of the CNS

must be able to overcome these barriers to treat CNS infections

Meningitis Definition

inflammation of the subarachnoid space or CSF

community acquired or healthcare associated

Is there a vaccine for meningitis?

most causative organisms of meningitis are vaccine-preventable

Most common meningitis causative organism

streptococcus pneumoniae

Ventriculitis Definition

inflammation of the ventricles of the brain

Encephalitis Definition

inflammation of the brain tissues

Brain abscess Definition

infection of the brain tissue characterized by well vascularized capsule

Streptococcus pneumoniae

Group B Strep (streptococcus agalactiae)

• gram positive

• the leading cause of neonatal meningitis → colonizes in GI and genitourinary tract of mothers

Neisseria meningitidis

• gram negative

• colonizes respiratory tract → very easily transmissible (spread by droplets)

  • example: Meningitis Belt in Africa

• clinical presentation: looks like large bruises

  • due to leakage of blood outside the blood vessels

Haemophilus influanzea type B

• gram neg

• respiratory tract

• uncommon due to vaccine

Listeria monocytogenes

• gram postive

• enters via GI - food

Foods assocaited w listeria

• unpasteurized milk

• soft cheeses

• raw produce

• deli meat, hot dogs

Risk factors for listeria

(not everyone will get meningitis due to listeria; just ppl w these risk factors)

• pregnancy

• infants less than 1 month

• adults over 50

• alcoholics with chronic liver disease

• immunocompromise

Meningitis hematogenous vs contiguous spread

Hematogenous: spread via invasion into the bloodstream and evasion of host defenses

Contiguous: infection at a place near CNS (nose or ear) that goes directly to the meninges

Meningitis Clinical Presentation

classic triad

• fever

• nuchal rigidity (neck)

• altered mental status

Meningitis Complications

Systemic (septic shock, disseminated intravascular coagulation, acute respiratory distress syndrome, septic arthritis)

Neurologic (impaired mental status, increased intracranial pressure, seizures, hearing loss)

Initial Meningitis Treatment

(assuming no brain mass)

dexamethasone + empiric antimicrobial therapy

Normal CSF

WBC: <5

Protein: <50

Glucose: 45-80

CSF/blood glucose ratio: 50-60%

Bacterial meningitis CSF

WBC: 1,000-5,000

Type of WBC: neutrophils

Protein: elevated

Glucose: low

CSF/blood glucose ratio: decreased

Multiplex PCR

identifies the causative organisms of meningitis or encephalitis

Meningitis Therapy

adjunctive dexamethasone (decreases inflammation) → empiric antimicrobials (bc its an emergency) → targeted antimicrobials (after receiving susceptibilities)

Limitation of Dexamethasone in Meningitis

decreased inflammation = decreased porousness of BBB = decreased penetration of antimicrobials

When to give dexamethasone

simultaneously with the first dose of antimicrobial OR 20 min before

discontinue if causative organisms are not S. pneumoniae

Agents that will never reach CNS/will not cross BBB

• aminoglycosides

• 1st/2nd gen cephalosporins

• doxycycline

• pip tazo

Ampicillin dose for CNS Penetrations

2g IV q 4hr

Ceftriaxone Ampicillin dose for CNS Penetrations

2g IV q 12hr

Empiric antimicrobials for 2-50 years old

Ceftriaxone and vanco

Empiric antimicrobials for 50+ years OR any age with risk factors for Listeria

Ceftriaxone, vancomycin, and ampicillin

Targeted antimicrobial drug of choice for streptococcus pneumoniae & duration of therapy

duration: 10-14 days

Targeted antimicrobial drug of choice for neisseria meningitdis & duration of therapy

duration: 7 days

Targeted antimicrobial drug of choice for haemophilus influenzae & duration of therapy

duration: 7 days

Targeted antimicrobial drug of choice for listeria & duration of therapy

duration: 21 days

Targeted antimicrobial drug of choice for group b streptococcus & duration of therapy

duration: 14-21 days

Bacterial pathogen associated with CSF shunts and drains

Coagulase-negative staphylococci (CoNS) Staphylococcus aureus (including MRSA) Gram-negative bacilli (including Pseudomonas aeruginosa) Cutibacterium acnes (formerly Propionibacterium acnes)

Bacterial pathogen associated with neurosurgery and poen/penetrating trauma

Coagulase-negative staphylococci (CoNS) S. aureus (including MRSA) Gram-negative bacilli (including P. aeruginosa)

Bacterial pathogen associated with closed trauma

Streptococcus pneumoniae Haemophilus influenzae Group A streptococcus (S. pyogenes)

Clinical Presentation of Hospital acquired meningitis and vasculitis

Fever, Headache, Nausea, Lethargy, Change in mental status, Seizures

Diagnosis of of Hospital acquired meningitis and vasculitis

Approach to Treatment of Hospital acquired meningitis and vasculitis

Empiric antimicrobials → targeted antimicrobials → intraventricular/intrathecal antimicrobials (only used when pt fails to respond to IV)

Treatment for CSF shunts and drains

Vancomycin + cefepime

Vancomycin + ceftazidime

Vancomycin + meropenem

Treatment for neurosurgery

Vancomycin + cefepime

Vancomycin + ceftazidime

Vancomycin + meropenem

Treatment for open/pentraring trauma

Vancomycin + cefepime

Vancomycin + ceftazidime

Vancomycin + meropenem

Treatment for closed trauma

Vancomycin + ceftriaxone

make flascards for slide 55

Intraventricular/intrathecal antimicrobials

direct instillation of antimicrobials into the CNS

Encephalitis Clinical Presentation

fever, headache, brain dysfunction → altered levels of consciousness, seizures, altered behavior, speech or movement disorders, etc

Encephalitis diagnosis

PCR, viral cultures, antibodies

Brain abscess clinical presentation

Brain abscess diagonsis

Brain CT

Brain abscess treatment

antimicrobial + neurosurgery to drain it

Brain abscess approach to therapy

imaging of brain abscess → empiric antimicrobial therapy → CT guided neurosurgery → targeted antimicrobial