Bacterial Meningitis Flashcards
Definition of meningitis
inflammation of the meninges (pia, arachnoid and dura mater)
how is meningitis practically defined?
abnormal number of WBCs– anything greater than 10 cells/mm cubed in CSF (but age dependent and person to person dependent)
meningitis is ofen (but not always) associated with what in terms of protein and glucose?
high protein (dead cells/proteinateous material/inflammatory proteins) and low glucose (protein material jams the active glucose transporters that pump glucose into the CSF, while glucose continues to diffuse out) in the CSF
why is it so dangerous to get an infection within the meninges?
the meninges are supposed to be a sterile site, so there are no inflammatory cells present to protect it
what inflammatory cells are most prevalent in viral meningitis? bacterial? fungal? parasitic?
viral: lymphocytic pleocytosis
bacterial (aka pyogenic– pus forming): PMN pleocytosis
fungal: lymphocytic pleocytosis
parasitic: eosinophilic pleocytosis
4 characteristics of viral meningitis
1) lymphocytic meningitis
2) bacterial cultures are negative
3) seasonality (late spring-fall = peak period in n hemishpere)
4) exposures to people with viral meningitis
Major viral causes of meningitis (5)
- enteroviruses
- Herpes virus
- HIV
- West Nile, Eastern equine, Western equine (arboviruses)
- Lymphochoriomeningitis (LCM) virus – board favorite though very rare!
aseptic meningitis– what is it and what is the cause?
when the meninges are inflammed and it’s not caused by pyogenic (pus forming) bacteria
Causes:
viruses, medications (NSAIDS, TMP-SMX), auto-immune dsorders (lupus), or oncologic causes (metastatic cancer)
symptoms you expect to see with Bacterial meningitis (6)
- headache
- fever
- photophobia
- nick stiffness (“meningisimus”)
- Positive Kernig’s and/or Brudzinski’s sign (kids 1-12 who can’t really express neck stiffness but have the musculature to resist movement)
- later confusion, stupor, coma
Brudzinki’s neck sign
tests for meningisimus (neck stiffness) by bending the head (think B from the name for brain) forward. It’s positive if the child brings their legs up to compensate for the pain
signo de kernig
tests for meningisimus (neck stiffness) by bending the knee (think K from the name for knee) toward the chest and then straightening the leg. It’s positive if the child curls in their head to compensate for the pain
Bacterial meningitis is usually community or hospital acquired?
generally community acquired
nosocomial
non-community acquired (aka hospital acquired) infection
normal path of bacterial infection in meningitis?
normally hematogenous spread (bacteria colonizes nasopharynx, invades tissue, gets into the blood stream and then into the CSF)
sometimes trauma that causes leaks in the CSF or a sinus infection in children can cause direct extension
ypical laboratory findings for bacterial meningitis: opening pressure WBC count %PMNs Prot: Glucose: CSF to serum glucose ratio gram stain culture
opening pressure: elevated to 200-500 mm H20
WBC count: VERY HIGH (1000-5000) (viral would be closer to 50)
%PMNs: 80% (viral would see lymphocytes, not PMNs)
Prot: high! 100-500 (n < 30)
Glucose: low! <40 mg/dl
CSF to serum glucose ratio: .4
gram stain: positive 60-90%
culture: 70-85%, but sometimes just bacteremia (in blood) but not in csf
why do most cases of meningitis present with low glucose and high protein?
protein is high bc cells are dying– lots of extra proteinatious material, and inflammatory proteins in CSF. These proteins get into the active glucose transporters which fall apart– glucose can’t get into csf anymore, but glucose is passively diffusing out —> low glucose in csf
what predictors are used to determine if the meningitis is bacterial? (5)
- positive gram stain
- csf protein > 80 mg/dl
- peripheral ANC (absolute neutrophil count) > 10,000 cells/mm cubed
- seizure at/before presentation
- CSF ANC > 1000 cells/mm cubed
pathophysiology of bacterial meningitis (4 components)
- alterations of BBB (blood brain barrier)
- cerebral edema, both vasogenic and cytotoxic
- Increased intracranial P (ICP)
- decreased perfusion P (Cerebral perfusion P = MAP-ICP)
3 mediators of cerebral inflammation in bacterial meningitis
- bacterial components
- inflammatory mediators
- host cellular response
bacterial mediators of inflammation in bacterial meningitis (3)
- capsule
- cell wall
- LPS
Inflammatory mediators of bacterial meningitis (5)
- TNF
- IL 1 and 6
- Platelet-activating factor
- Prostaglandins
- Complement factors
Host cell mediators of inflammation in meningitis (3)
- PMNs
- CNS macrophages
- Endothelial cells
the successful invasion by bacteria of the CNS and establishment of infection/meningitis requires: (4 steps)
- colonization of mucosa (gen nasopharynx)
- invasion of IV space
- cross BBB
- survival/replication in CSF
most common causes of bacterial meningitis
LEGSNH listeria monocytogenes E (E coli-- which is not one of the common causes, but is a less common cause) Group B strep (streptococcus agalactiae) Streptococcus pneumoniae Nisseria meningitidis Haemophpilus influenzae
Less common causes of bacterial meningitis
Klebsiella, E coli, Serratia, Psudomas, Salmonella, Nosocomial (40% cases among adults), Spirochetal: lyme disease (borrelia burgdorfen) and syphilis (treponema pallidium)
what's the cause? 12 month old child lethargy fever large red, flat facial rash that appeared 1-2 days prior LOC tachycardic RR and BP normal only arouses upon noxious stimuli depressed mental status on neuro exam
Prior H/O:
ear infection 1 mo ago, txt w/abx
no H/O vaccines
Haemophilus influenza type B (HIB)– accounted for 70% of all cases of bacterial meningitis in childrel
HIB -
size, gram stain, defining capsule characteristics
small
gram neg
typeable (has a capsule) with PRP (polyribitol ribose phosphate)
*there are other forms of HI that are nontypeable (nocapsule)– immunity probably strain dependent (recurrent colonization/infection)
clinical spectrum of Haemophilus influenzae (5)
- Mucosal disease
- otitis media, sinusitis (often non-typeable)
- pneumonia (oftennon-typeable)
- epiglottitis
- metastatic foci (usually typeable type B)– septic arthritis, meningitis
*immunity probably strain dependent (recurrent colonization/infection)
Immunity to HIB
Anti-PRP (capsule component) Abs activate comp and opsonic activity
maternal anti-PRP AB wanes at 6-24 months —> kids start getting sick
The HIB vaccine contains what and achieved what?
contains PRP-conjugate, it decreased nasopharyngeal colonization (“carriage”) and invasion, so herd immunity!
HIB source: spread to host: adhesion to host: invasion/spread within host: escape from host defenses: damage to host/manifestations:
HIB
source: humans, mostly children
spread to host: nasal secretions
adhesion to host: pili, other
invasion/spread within host: Nasopharynx (NP) colonization —> otitis, pneumonia, epiglottitis and/or invasion of blood, replication, invasion of CSF/other metastatic site
escape from host defenses: mostly via capsule
damage to host/manifestations: otitis, pneumonia, epiglotittis, cellulitis, bateremia, meningitis, osteomyelitis, or arthritis
post HIB vaccination, the median age for meningitis changed from 15 mo to ____ and the two main causes of bact. meningitis became
25 yo
S. pneumoniae and N, meningitidis
what is the cause?
18 m/o
HO high fever and ear infection 2 days prior (though generally well looking)
fever high in spite of Abx admin
less active/listless
vomiting
Strep pneumoniae
strep pneumoniae:
gram stain/shape
capsule?
gram positive diplococci
encapsulated (w/over 90 serotypes)
Streptococcus pneumoniae source: spread to host: adhesion to host: invasion/spread within host: escape from host defense: damage to host/manifestations:
Streptococcus pneumoniae
source: humans (mostly other kids), nonhuman primates/horses
spread to host: nasal secretions
adhesion to host: PAF receptor, pili, other
invasion/spread within host: NP colonization —> otitis, pneumonia, invasion of blood stream, replication, CSF invasion/other metastatic sites (joints/bones)
escape from host defense: thick polysac. capsule (like HIB)
damage to host/manifestations: otitis, pneumonia, bacteremia, meningitis (high mortality and morbidity!)
Streptococcus pneumonia generally affects people of what age? when?
very young and the elderly (who get it from their grandkids)
seasonal colonization– highest mid winter
6 things that make you more susceptible to strep pneumonia
- asplenia
- hypogammaglobulinemia
- proteinuric conditions
- multiple myeloma
- diabetes
- chronic disease in general
what mediates the intense inflammation associated with strep pneumonia?
cell wall components and pneumolysin
is there a vaccine for pneumococcus (strep pneumoniae)?
yes–
- conjugate vaccine, 13 valent for kids and adults– very expensive- not in most dvping countries
- polysac vaccine (23 valent- adults)
What is the cause: college student NK PMH felt "cold" left eye was painful/draining fluid (conjuctivitis/infection of the eye) LOC fever tachycardic low BP high RR diffuse non-blanching rash (petechiae) on extremities coalescence of joints poor perfusion to extremities, slow cap refill no detectable meningismus
Neisseria meningitidis Group C
Neisseria meningitidis
gram stain and shape?
encapsulated?
who does it affect?
Neisseria meningitidis:
gram neg doplococci (adjacent sides are flat)
encapsulated
leading cause of meningitis in children/young adults and epidemic in colleges, military bases and subsaharan africa
clinical spectrum of invasive meningococcal disease associated with neisseria meningitidis (4)
- bacteremia (aka meningococcemia) w/ and w/out meningitis
- meningoencephalitis
- meningitis with and w/out documented bacteremia
- shock syndrome can dominate (hypotension, DIC (disseminated IV coagulopathy), Waterhouse-Fredericksen syndrome (bilateral adrenal hemorrhage with purpura fulminans)
Waterhouse-Fredericksen syndrome
bilateral adrenal hemorrhage with purpura fulimans
a possible shock syndrome response to Neiserria meningitidis that can lead to death due to non-func kidneys
risk factors for Neisseria Meningitidis (4)
dry-arid conditions
crowding
carriage
complement deficiency (terminal components C5-9)– with this deficiency, one is more likely to get it but less likely to die
Txt issues assoc with Neisseria meningitis (meningococcal) timeframe: Abx: mortality (2): morbidity (2): controversial features (4):
speed is essential
most strains highly susceptible to penicillin (PCN) but resitance emerging
2 causes of mortality (CNS herniation or shock)
2 types of morbidity: CNS vs other organ failure (skin, renal, cardiac from shock)
controversial: role of steroids, activated prot C, plasmaphareisis, anti-LPS modalities
Summary Neisseria meningitidis (meningococcal) source: spread to host: adhesion to host: invasion/spread within host escape from host defenses: damage to host/manifestations
source: humans
spread to host: nasal secretions
adhesion to host: pili, other
invasion/spread within host: NP colonization can lead to conjunctivitis, pneumonia and/or invasion of bloodstream, replication, invasion of CSF or just remain in bloodstream
escape from host defenses: capsule, surface prots (fHbp, PorA) to evade complement
damage to host/manifestations: conjunctivitis, pneumonia, bacteremia, meningitis, purpura fulminans (PF- hemorrhagic condition), Waterhouse-Fredericksen (hemorrhaging to adrenals), petechiae
cause of meningitis? 21 day old fussy low grade temp suddenly grey, unresponsive bulging fontanelle
Group B strep (streptococcus agalactiae)
Group B strep/ streptococcus agalactiae gram stain/shape lancefield grp different serotypes? surface prot ags?
Gram pos diplococci encapsulated Lancefield group B (beta hemolytic) many serotypes has surface prot Ags
clinical manifestations of group be strep (strep agalactiae)
puerperal sepsis (bacterial infection contracted by women during childbirth or miscarriage) septicemia and meningitis in neonates and infants 65 with underlying medical conditions
sources of group b strep (strep agalactiae):
principal reservoir = GI tract Gu colonization (risk factors = gender, race, age, frequency of sexual intercourse, diabetes) vaginal colonization (vertical transmission to newborns)
risk factors for vert. transmission of grp b strep (strep agalactiae)
maternal colonization (bacteruria = marker of heavy colonization and maybe lower immunity?)
ROM (rupture of membane) or delivery 38 degrees C
amnionitis
ROM (rupture of membrane) > 18 hrs
2 types of group B strep (strep agalactiae)
early onset disease and late onset disease
Description of early onset Group B strep: timing: manifestations meningeal signs: prevention:
timing: within few hours of birth
manifestations: lethargy, poor feeding, hypothermia, grunting, hypotension, apnea, and overwhelming disease (pneumonia, CNS invasion, sepsis)
meningeal signs: no specific signs
prevention: with peripartum prophylaxis (PPP) to GBS+ mothers
The utility of steroids in treating bacterial meningitis
Steroids given to adults and (now) children in treating meningitis caused by Hib and Strep. pneumoniae
However, according to slide 62, the use of steroids in treating meningococcal disease remains controversial
Being on steroids = a risk factor for meningitis by Listeria monocytogenes
