T5 - IE5 - Infectious Diseases I - Fong (Merna) - Meningitis

Meningitis often presents with _________ headache and _______ neck

- severe (headache)

- stiff (neck)

Meningitis clinical presentation figure

Meningitis

inflammation of the meninges

Epidemiology: risk factors and mortality rates widely vary depending on the causative ______________ and _____ ___________

- microorganism

- age group

Meningitis is a disease caused by __________ of the protective membranes covering the brain and spinal cord known as the __________

- inflammation (of the protective membranes)

- meninges

Meningitis is a disease caused by inflammation of the protective membranes covering the ______ and _______ ______ known as the meninges.

- (covering the) brain

- spinal cord

Meningitis can be ____-__________ because of the __________ to the brain and spinal cord; therefore the condition is classified as a medical emergency

- life-threatening

- proximity (to the brain and spinal cord)

Meningitis can be life-threatening because of the proximity to the brain and spinal cord; therefore the condition is classified as a ___________ _________

- (classified as a) medical emergency

Meningitis can strike quickly and kill within ________, so _______ medical attention is essential

- (kill within) hours

- urgent (medical attention is essential)

Meninges is the system of ____________ which develops the central nervous system

- (system of) membranes

3 Layers of the meninges

Dura mater

Arachnoid mater

Pia mater

Subarachnoid space is located between the arachnoid and the Pia mater

Layers of the meninges: subarachnoid space is located between the ____________ and the ______ mater

- Arachnoid

- Pia (mater)

Meninges layers figure

Encephalitis

inflammation of the brain tissue itself

Meningoencephalitis

inflammation of the meninges and brain

(some combination of both)

Cause of meningitis

Viral

Bacterial

Fungal

Parasitic / protozoal

Viral meningitis is more ________ but bacterial meningitis can be more ___________

- (more) common

- (more) dangerous

Pathogenesis of bacterial meningitis diagram

Pathogenesis of bacterial meningitis: bacterial meningitis starts with a _____________ ______ by the pathogenic bacterial infection

- Nasopharyngeal colonization (by the pathogenic bacterial infection)

Pathogenesis of bacterial meningitis: bacterial meningitis starts with a nasopharyngeal colonization by the ___________ ______ __________

- pathogenic bacterial infection

There is invasion of the epithelium

Pathogenesis of bacterial meningitis: bacterial meningitis starts with a nasopharyngeal colonization by the pathogenic bacterial infection

Then, there is an _____________ of the ____________

- invasion

- (of the) epithelium

Followed by invasion of the blood

Pathogenesis of bacterial meningitis: bacterial meningitis starts with a nasopharyngeal colonization by the pathogenic bacterial infection

Then, there is an invasion of the epithelium followed by invasion of the ________

Bacteria is ____________ into the blood stream and bacteria is then further _____________

- (invasion of the) blood

- phagocytized (into the blood stream)

- (further) dissemination

This dissemination may enter the CSF and tissues

Pathogenesis of bacterial meningitis: bacterial meningitis starts with a nasopharyngeal colonization by the pathogenic bacterial infection

Then, there is an invasion of the epithelium, then blood, further dissemination into the ___________ ______ and tissues.

In the CSF, _______ multiplication, of the bacteria due to the availability of the __________

- (dissemination into the) cerebrospinal fluid

- rapid (multiplication)

- (availability of the) nutrients

Risk factors of bacterial meningitis

Age

- children < 5 years ( particularly < 2 years)

- meningitis is severe in neonates (< 1 month)

- elderly

Large group communities (schools, campuses)

Immunocompromised

Smoking

Risk factors of bacterial meningitis - age: children ___ _____ years particularly ___ __ years

- < 5 (years)

- (particularly) < 2 (years)

Risk factors of bacterial meningitis - age: meningitis is severe in ___________

- neonates

< 1 month

Risk factors of bacterial meningitis - age: other large age group are the _________

- (are the) elderly

Risk factors of bacterial meningitis - large ______ ______________

- (large) group communities

e.g., schools, campuses

Risk factors of bacterial meningitis - those that are ____________ and/or ____________

- immunocompromised

- smoke

Complications of bacterial meningitis

cerebral edema

concentration / memory impairment

hearing loss of deafness

seizures

death

Clinical presentation of Bacterial Meningitis Diagram

Clinical presentation of Bacterial Meningitis

Fever

Neck stiffness (nuchal rigidity)

Altered mental status (AMS)

Headache

Nausea

Rash

Photophobia

Neurological deficits

Nuchal rigidity

neck stiffness

AMS

altered mental status

Testing for nuchal rigidity

Kernig's sign

Brudzinski sign

Nuchal rigidity tests: Kernig's sign: is assessed with the patient lying _______, with the hip and knee ______ to 90°.

In a patient with a positive Kernig's sign, _____ limits passive __________ of the knee

- (lying) supine

- flexed (to 90°)

- pain

- (limits passive) extension

Kernig's sign

inability to extend legs

Nuchal rigidity tests - Brudzinksi sign: positive sign occurs when flexion of the neck causes __________ ________ of the knee and hip

- involuntary flexion (of the knee and hip)

Classic triad of meningitis

Fever

Nuchal rigidity

Altered mental status

Diagnosis of meningitis - lumbar puncture

invasive procedure used to remove a sample of cerebrospinal fluid (CSF) from the subarachnoid space in the spine

Also called a "spinal tap"

Diagnosis of meningitis - lumbar puncture: is an invasive procedure used to remove a sample of cerebrospinal fluid (CSF) from the _____________ ____ in the ________

- subarachnoid space

- (in the) spine

Also called a "spinal tap"

CSF

cerebrospinal fluid

Spinal tap

another name for lumbar puncture

Diagnosis of meningitis - lumbar puncture figure

Diagnostic testing for bacterial meningitis

LP can cause brain herniation, need CT to ensure

Lumbar puncture (LP) required for definitive diagnosis

Getting CT delays the LP, which delays antibiotics

Delayed antibiotics lead to worse outcomes

Order of diagnostic testing for meningitis

1) CT (to ensure no risk of herniation)

2) LP required for definitive diagnosis

3) Antibiotics (delayed antibiotics lead to worse outcomes

Diagnostic testing for bacterial meningitis: LP can cause _______ ______________, need CT to ensure

- (can cause) brain herniation

Diagnostic testing for bacterial meningitis: Lumbar puncture (LP) required for _____________ ____________

- (required for) definitive diagnosis

LP

lumbar puncture

Diagnostic testing for bacterial meningitis: Getting _____ delays the ____, which ________ antibiotics

- (Getting) CT

- (delays the) LP

- delays (antibiotics)

Diagnostic testing for bacterial meningitis: delayed antibiotics lead to ___________ outcomes

- worse (outcomes)

CSF findings chart in meningitis

Bacterial meningitis CSF findings - color

clear-turbid

(i.e., from clear to cloudiness)

Bacterial meningitis CSF findings - opening pressure

Elevated (opening pressure)

Bacterial meningitis CSF findings - WBC count

≥ 1000 cells / mL (mainly PMNs)

Bacterial meningitis CSF findings - glucose

< 40 mg/dL

Whereas, in normal and viral it is 45-80 mg/dL; in bacterial meningitis, the bacteria will consume glucose

Bacterial meningitis CSF findings -protein

> 100 mg/dL

4 Bugs of Bacterial Meningitis (from most common to least)

Streptococcus pneumonia (58%)

- GBS (18.1%)

Neisseria meningitidis (13.9%)

Haemophilus influenza (6.7%)

Listeria monocytogenes (3.4$)

Bacterial meningitis figure

Most common bug in bacterial meningitis

Streptococcus pneumoniae (58%)

- GBS (18.1%)

GBS

Streptococcus agalactiae

Common pathogens of bacterial meningitis by age: < 1 month

S. agalactiae (GBS)

E. coli

Listeria monocytogenes

Klebsiella

< 1 month

Common pathogens of bacterial meningitis by age: 1-23 months

S. pneumoniae

N. meningitidis

S. agalactiae (GBS)

E. coli

H. influenzae

1-23 months

Common pathogens of bacterial meningitis by age: 2-50 years

S. pneumoniae

N. meningitidis

2-50 years

Common pathogens of bacterial meningitis by age: > 50 years

S. pneumoniae

N. meningitidis

L. monocytogenes

> 50 years

Empiric meningitis treatment for < 1 month

Ampicillin

plus

Cefepime*

OR

Aminoglycoside

empiric treatment: age < 1 month

Neonates should _______ ___ _______ ceftriaxone due to the increased risk of biliary sludging (solids that precipitate from bile) and kernicterus (brain damage from high bilirubin)

- not be given (ceftriaxone)

Neonates should not be given ceftriaxone due to increased risk of ________ _______ and _________

- biliary sludging

- kernicterus

Biliary sludging = sludge that precipitate from bile

Kernicterus (brain damage from high bilirubin)

Empiric meningitis treatment for Age 1-23 months

ceftriaxone

plus

vancomycin

empiric treatment age 1-23 months

Empiric meningitis treatment for age 2-50 years

ceftriaxone

plus

vancomycin

similar to age 1-23 months

Empiric meningitis treatment for age > 50 years OR immunocompromised

ceftriaxone

plus

vancomycin

plus

ampicillin

treatment for ages > 50 years or immunocompromised

In special populations, we add ____________ _________

- Pseudomonas coverage

Anti-pseudomonal β-lactam: cefepime, carbapenems, ceftazidime

Anti-pseudomonal β-lactams

cefepime

ceftazidime

carbapenems

Special populations for meningitis

Basilar skull fracture

Penetrating trauma

Neurosurgery

CSF shunt

Immunocompromised

Why vancomycin: NOT for __________ but ___ ____________ resistance to ceftriaxone (10%)

- (NOT for) MRSA

- S. pneumoniae (resistance)

Antibiotic dosing in meningitis: generally speaking, be ____ ___________

- very aggressive

This is required for CSF penetration

Antibiotic dosing chart: normal vs. meningitis

Ampicillin normal dosing and meningitis

2g IV q4-6

Meningitis:

2g IV q4h

Ampicillin meningitis dosing

Ceftriaxone normal dosing and meningitis

1-2 g IV q24H

Meningitis:

2g IV q12H

Ceftriaxone meningitis dosing

IMPORTANT

Vancomycin normal dosing and meningitis

Trough: ~15 mg/L

Meningitis dose

Trough ~18-20 mg/L

Vancomycin meningitis dose

Cefepime normal dosing and meningitis

1-2 g IV q8H

Meningitis dose

2 g IV q8H

Cefepime meningitis dose

Antibiotic dosing in meningitis: can even consider ___________ dosing of some drugs such as ____________ and ____________

- intrathecal (dosing)

- vancomycin

- aminoglycosides

NOT β-lactams

Common gram positive bacteria in meningitis

Streptococcus pneumoniae

Listeria monocytogenes

Common gram negative bacteria in meningitis

Neisseria meningitidis

Haemophilus influenzae

Meningitis duration of treatment: gram-negative tends to be ______ _________

- (tends to be) 7 days

e.g., Neisseria meningitidis, Haemophilus influenzae

Meningitis duration of treatment: Streptococcus pneumoniae

10-14 days

Meningitis duration of treatment: Listeria monocytogenes

≥ 21 days

Meningitis duration of treatment: Haemophilus influenzae

7 days

similar to Neisseria meningitidis

Meningitis duration of treatment: Neisseriea meningitidis

7 days

similar to Haemophilus influenzae

Role of corticosteroids in meningitis: ____________; corticosteroids inhibit the production of inflammatory cytokines such as ______ and ____-____

- controversial

- TNF

- IL-1

Role of corticosteroids: use _____________ 0.15 mg/kg q6H for ___-____ days, initiated 10 to 20 minutes prior to or concomitant with the first dose of antibiotics

- dexamethasone

- 2-4 (days)

Role of corticosteroids: use dexamethasone 0.15 mg/kg q6H for 2-4 days, initiated 10 to 20 minutes ________ ___ or __________ _____ the first dose of antibiotics

- prior to

- concomitant with (the first dose)

i.e., use before or WITH the first dose of antibiotics

Role of corticosteroids: clinical outcome is __________ to improve if dexamethasone is given ________ the first dose of antimicrobial

- unlikely (to improve)

- (given) AFTER

Vaccines available for meningitis

S. pneumoniae

- PPSV23 and PCV13

N. meningitidis

- Meningococcal conjugate vaccines (Men ACWY): 11-12 years, 16 years

- Serogroup B meningococcal vaccine (MenB): 16-23

H. influenzae Type B (Hib)

- schedule: 2 months, 4 months ± 6 months, 12-15 months

- has dramatically reduce the incidence of invasive Hib disease

Listeria:

- NO vaccine available

Hib Vaccine Result Chart

Antibiotic prophylaxis: target at preventing ____ ____________ spread only (not the _____ bugs)

- N. meningitidis (spread only)

- (not the) other (bugs)

Antibiotic prophylaxis: generally for ____________ contacts / ____ ______ contact

- household (contacts)

- very close (contact)

Antibiotic prophylaxis: recommended agents

Rifampin 600 mg PO q12H x 2 days

Ciprofloxacin 500 mg PO x 1 dose

Ceftriaxone 250 mg IV x 1 dose

Summary: meningitis usually presents with ______, _________, ________ ________ and _________ _________ _________

- fever

- headache

- nuchal rigidity

- altered mental status

Summary: diagnosis is __________ with a lumbar puncture (_________)

- confirmed (with a lumbar puncture)

- LP