MID 4 - Meningitis / Flashcards
(25 cards)
What organisms are most likely to cause meningitis in neonates and what is their gram staining pattern?
1) Strep Pnemoniae (Gram+)
2) Group B Strep (Gram+ coccus)
3) E. coli KI (Gram- bacillus)
3) nisseria meningitis
4) listeria monocytogenes
5) H. influenzae
What is the pathogenesis of Group B Strep meningitis?
1) baby aspirated from birth canal
2) High grade bacteremia due to poor neonatal host defenses.
3) bacteria enters meninges via meningeal endocytosis.
4) intracellular replication, requiring prolonged therapy.
What part of bacteria is basis for effective vaccine epitope?
polysaccaride capsule.
What is special about meninges that make it dangerous?
Little room for inflammation
No complement
minimal Ig
No PMN
What organisms cause meningitis in neonates and what is the site of infection?
Group B Strep - commensal flora of mother, aspirated from birth canal
E. coli K1 - maternal fecal flora, ascending infection.
Listeria monocytogenes - mother ingests it in contaminated food, flu-like illness.
Enterococci
Salmonella - fecal contamination
Why was it more difficult to develop a vaccine to GBS as opposed to other strep?
polysaccharide capsule mimics terminal sialic acid of mammalian cell polysaccharide.
Which neonates are at highest risk for Group B Strep?
1) colonized moms
2) pre-term
3) multiple births.
What are major virulence factors in pneumococcus?
cell wall fragments lead to inflammation.
pneumolysins cause neuronal apoptosis
sialidase that acts as an adhesin.
Describe the pathophysiology of meningitis
inflammation due to PMNs
Edema due to elevated CSF protein
Increased intra-cranial pressure leading to loss of perfusion
breakdown of blood-brain barrier
loss of auto regulation, including BP control.
How does pneumolysin stimulate neuronal apoptosis?
Inflammasome activation via IL-1 and IL-18.
What is primary goal of therapy in meningitis?
Reduce inflammation - steroids. Give prior to antibiotics in order to decrease secondary increase in TNF due to release of bacterial cell wall fragments.
What genetic defects can cause recurrent invasive pneumococcal disease in otherwise healthy patients?
IRAK4 and NEMO mutations associated with recurrent disease, code for proteins important in PAMP pathways.
How is N. meningitides taken up and how is it killed?
spread via droplets, aerosols, rapid uptake by epithelial cells - receptor mediated endocytosis. Encapsulated gram- species requires IgG + complement to phagocytose.
How do you diagnose meningitis?
Lumbar puncture:
gram stain for bacteria
Look for PMNs
Look for elevated protein and low glucose due to problems in blood-brain barrier.
What are the sequllae of meningitis?
hearing loss; seizure disorder; major neurological dysfunction, ADD, behavioral abnormalities, minor neurological dysfunction.
Macrolides:
1) spectrum?
2) common drugs?
3) mechanism of action?
1) broad-spectrum
2) erythromycin, clarithromycin, azithromycin
3) Inhibits formation of 50S ribosome, blocking trans-peptidation or translocation.
What are the common mechanisms of resistance to macrolides?
1) decreased permeability of envelope
2) erm gene encodes methylase that alters ribosomal subunit and thus macrolide binding.
3) efflux pump.
What organisms are generally sensitive to erythromycin?
Gram+ S. pneumoniae, virdans group strep, strep A/B, S. aureus.
Gram- Bordetella pertussis, Neisseria, campylobacter, legionella,
miscellaneous mycoplasma/ ureaplasma, chlamydia, treponema.
What benefits does Clarithromycin and azithromycin have relative to erythromycin?
increased activity against H influenza, E coli, campylobacter, helicopter pylori, mycobacterium avid intracellular, toxoplasma. Longer half life.
Azithro has better gram- activity
carithro as better gram positive activity.
What are the indication for macrolide use?
community acquired pneumonia otitis media pertussis (treatment and prophylaxis) campylobacter gastroenteritis Alternative agent for strep , thematic fever prophylaxis, anthrax.
What are macrolide toxicity?
GI symptoms, including cramping and increased motility; inhibits cytochrome P450 enzymes, so drug interactions must be closely monitored.
Risk of sudden death with prolonged QT interval; cholestatic hepatitis.
Erythro can cause pyloric stenosis in infants.
Clindamycin:
1) mechanism of action?
2) spectrum?
3) toxicity?
4) Indications?
1) similar to macrocodes
2) bacteriostatic against Gram+ and anaerobes, useful against bone infections.
3) diarrhea, classically predisposing to C. difficile colitis.
4) penicillin-resistant anaerobic infections, S. aureus.
aminoglycosides:
1) mechanism of action?
2) spectrum?
3) toxicity?
4) indications?
1) Diffuses through porin channels in outer membrane, interferes with mRNA translational accuracy via 30S ribosome.
2) bactericidal with primary activity against aerobic gram-, some activity against strep and staph.
3) narrow therapeutic window with significant toxicity including nephrotoxicity, ototoxicity.
4) Used as empiric therapy and as second agent against serious gram negatives, enterococcal endocarditis, pseudomonas infections.
What are the mechanisms of resistance against ahminoglycosides?
Enzymatic modification by adenylation, phosphorylation, or acetylation.
Anaerobes intrinsically resistant because they lack O2 dependent transport system.
