In what area does meningitis occur?
What sorts of immune response are packing in the subarachnoid space?
antibody and complement production = no phagocytosis
What are the typical clinical symptoms for meningitis?
fever (but less likely in older individuals)
maybe seizures and altered mental status
What test can be used to differentiate between bacterial and viral (and other) types of meningitis?
CSF analysis - WBC
bacteria will have more PMNs
viral will have more lymphocytes
both will have elevated protein, but bacterial will have DECREASED GLUCOSE
Is aseptic meningitis syndrome usually viral or bacterial?
viral - can also be noninfectious like with some drugs
What is the treatment for aseptic meningitis syndrome?
supportive therapy - most recover on their own but it can be fatal in the neonatal period
Do you need to do PCR confirmation of the organism in aseptic meningitis?
What group of viruses are the vast magority of viral meningitis cases associated with?
What are some examples of enteroviruses?
human enteroviruses 68-71
Besides enteroviruses, what are some viruses that have been associated with viral meningitis?
Lymphocytic choriomenginitis virus
What is the risk factor for lymphocytic choriomeningitis virus?
exposure to rodents
What type of viruses are enteroviruses?
single stranded + sense RNA
How are enteroviruses transmitted? WHen in the year?
usually late summer and fall
Which has more neck stiffness, viral or bacterial meningitis?
Which has a more acute onset, viral or bacterial meningitis?
What is the go-to drug for bacterial meningitis empiric treatment?
ceftriazone (3rd generation cephalosporin)
What drug should you add if MRS or resistant strep?
Pseudomonas or AIDS?
MRSA = vanco
HSV = acyclovir
Pseudomonas = cefepime
Listeria = ampicillin
What is the concern with using Ceftraxone? Why is it utilized for CNS infections>
It's broad spectrum, so the issue is C. diff, but bacterial meningitis is life threatening, so it's worth it
Particulalry useful in the CNS because it has less of an inhibitory effect on GABA release than other beta-lactams, so the risk of seizure is lower
What is the pimarily mechanism of action for ceftriaxone?
It blocks the transpeptidation of peptidoglycan, thus inhibiting cell wall synthesis
binds to the penicillin binding proteins on transpeptidase
What is the main mechanism of action for vancomycin?
blocks the translygosylation of peptidoglyan by binding to NAM and NAG - cell wall inhibitor
What is the spectrum for ceftriaxone? How does resistance develop?
It's used for streptococci and more serious gram negative infections
can cross the blood brain barrier
Resistance thorugh beta-lactamases and alteration of the PBP binding site
What are the three most common bacteria causing meningitis? For adults? FOr 11-12 yr olds?
Streptococcus pneumonia (adults)
Neisseria meningiditis (11-17 yr olds)
Haemophilus influenza type B
Where does the initial bacterial infection with H. influenza, N. meningiditis, or S. pneumonia occur?
typically in the nasopharynx
What are the 5 main virulence factors that play importnant roles in bacterial meningitis?
the capsule (neisseria, haemophilus and streptococcus)
IgA protease (Neisseria, Haemophilus, strep)
Pili for adhesion (neisseria an dhaemophilus)
Endotoxin (neisseria and haemophilus)
Outer membrane proteins (Neisseris and Haemophilus)
The LPS of Niesseris meningitidis is structured slightly differently. WHat is the significance of this and what is it called?
It's called LOS and it looks like sphingolipids, so it's recognized as self
What occurs with LPS endotoxin shedding?
It activates macrophages to release NO, causing hypotension and shock. Also IL-1, for fever.
May lead to disseminated itnravascular coagulation = purpuric skin rash
What are neisseria meningiditis outbreaks associated with?
overcrowding in the dorms, especially during late winter or early spring
How is Neisseria meningiditis transmitted?
How many serogroups of neisseria meningiditis are covered by the meningococcal meningitis?
4 out of 13
What shape is streptococcus pneumonia?
gram positive diplococci in a lancet shape
In pneunococcal meningitis, what can you give prior to antibiotic treatment to reduce hearing loss and other neurological sequelae in adults?
What is hte most common cuase of bacterial meningitis in individuals over 2 years of age?
What does hemophilus influenza b look like on histology?
a gram negative "coccoid" rod
What is the vaccine for Haemophilus influenza b meningitis?
the Hib vaccine
(a B capsular polysaccharide)
What can hemophilus influenza type b infections be followed by?
What are the 3 more common bacterial imeningitis causes in patients under 2 months old?
Group B streptococcus
WHy is the risk of infection from the most common causes be lowe rin infants?
What is another name for group B streptococcus?
(lancefield group B antigen)
Where is Group B strep normally found and how do infants get it?
GI and GU tract flora
infants get it through vertical transmission either in utero or during vaginal delivery
How do we avoid transmission of Group B strep to infants in the US?
We screen pregnant women and give penicillin G as prophylactic treatment before birth
What is the CAMP reaction that comes with grou B strep and staph aureus?
a synergistic hemolysis of RBCs by phospholipases from gruop B strep and the betal-hemolysins of Staph aureus
What does listeria monocytogenes look like on histology?
gram positive rod
With listeria monocytogenes, you don't really get neck stiffness, but you do get___
How is listeria monocytogenes transmitted? How does this relate to advice given to pregnant women?
consumption of contaminated food
this is why pregnant women aren't suposed to drink unpasteruized milks, cheese, or deli meats
For Listeria, ____ induces phagocytosis by epitherlial cells of the GI tract, while phospholipase and _____ allow excape from the vacuole
Internalin induces phagocytosis by epithelial cells of the GI track, and phospholipase and listeriolysin O allow escape from vacuole
What protein facilitates speudopod spread between adjacent cells for listeria?
What polysaccharide in the capsule of E. coli prevents fusion with the lysosome?
K1 capsular polysaccharide
IF the E coli strain is expression a beta lactamase, what should you add to the ceftriazone?
What are some common bacterial causes of CHRONIC meningitis?
What are some common fungal causes of chronic meningitis?
What percentage of miliary TB will have meningeal involvement?
What is the treatment for mycobacterium tuberculosis infection? Why does it take so many drugs?
Isoniazid to inhibit mycolic acid (acetylation by liver - fast acetylators will require higher dose)
RIfampin - inhibits RNA polymerase
Ethambutol - binds to arabinosyl transferase to inhibit cell wall synthesis
pyrazinamide - unknown mechanism
Takes 4 because mycobacterium develop immunity quickly - less likely to be able to do it against 4 at once
How is crytococcus neoformans transmitted?
inhaled as spores, dissmeinated hematogenously to CNS in immunocompromised individuals
What stains/tests are needed to diagnose crytococcus?
india ink stain
latex agglutination test
Where in the world is crytococcus neoformans most common?
What is the treatment for crytococcus meningitis?
amphotericin and flucytosine until culture negative
followed by fluconazole for 3-12 months or rest of life in immune compromise
How does amphotericin B work? Why is it highly toxic? How does it get to the BBB? Spectrum? Resistance?
It binds ergosterol to create holds in fungal membrane
Broad spectrum against systemic fungal infections - yeasts and molds
The liposomal form can cross the BBB
It's toxic because it binds patient's cholesterol and decreases renal blood flow, potentially causing permanent destruction of basement membrane
Resistance is rare, but reduced ergosterol in membrane
How does flucytosine work? Spectrum? Toxicity? Resistance?
It's an antimetabolite that is selectively taken up by fungi and converted to 5-FU to interfere with DNA and RNA synthesis
Narrow spectrum - yeast only, like candida albicans and cryptococcus
Toxic because of bone marrow suppression
Resistance is thorugh loss of converting enzymes or transporters - cotreat with amphotericin B
How do the azoles like fluconazole work?
they bind the fungal p-450 enzyme to block production of ergosterol
spectrum - dimorphic fungi and yeast
Toxicity - drug-drug interactions, hepatotosicity, neurotoxicity, alters hormone synthesis so AVOID during pregnancy
Resistance is thorugh altered cytochrome p450 and efflux transporters
What type of agar can hemophilus influenza b grow on?
chocolate agar, but not blood agar