Week 3 Flashcards
Potential negative consequences of antibiotic use
toxicity, allergic reactions, resistance
Common toxicities associated with antibiotics
Beta-lactams: allergic reactions, anaphylaxis
Aminoglycosides: nephrotoxicity
Vancomycin: Red Man’s Syndrome
Fluoroquinolones: Achilles tendon rupture
Linezolid: bone marrow suppression
Daptomycin: myopathy
Trimethoprim-sulfamethoxazole: Stevens-Johnson Syndrome
Factors driving resistance
treatment of human illnesses with antibiotics, fecal/oral, carniverous consumption
Resistance mech.
efflux pumps, alteration of porins, microbial enzymes, mutations of target molecules, increase in binding sites (weaken availability for active site), transformation of prodrugs into moieties
Describe 2 laboratory methods used to establish whether an organism is sensitive or resistant to a specific antibiotic
- Kirby Bauer Method (measures MIC, uses zones of growth inhibition)
- Broth dilution test (can get MIC and MBC)
- E-test (with antibiotic gradient in a strip)
Describe what it means for beta-lactam agents to have time-dependent killing and how this characteristic influences how we dose them
Antibiotics with time dependence: beta-lactams, clindamycin, linezolid, vancomycin
Calculated as Time/MIC
How to dose- does several times a day, short infusion periods across the day
Describe what it means for an aminoglycoside to have concentration-dependent killing and how this characteristic influences how we dose them
Antibiotics with concentration-dependence: aminoglycosides
Calculated as AUC/MIC
How to dose- one big dose per day
Epidemiology of malaria
3% of world population infected (~220 million)
Endemic in 100+ nations
Congo and Nigeria ~40% of cases worldwide
90% of malaria-related deaths in sub-saharan africa
Identify the mammalian life cycle stages for Plasmodium spp.
Vector- Anopheles mosquito
Sporoziotes injected in blood meal, infection of Kupffer resident macrophages, release of merozoites, differentiation into trophozoite upon invasion of rbc’s, then schizont, then merozite or gemotcyte which is taken back into mosquito gut via bloodmeal to complete sexual cycle
Kupffer cell invasion and evasion of the immune repsonse
Kupffer cell invasion- thrombospondin and properdin receptors
RBC invasion- surface glycoproteins and lectins
Evasion of the immune response-
1) cytoadherence to endothelial cells evades clearance (ICAM-1, VCAM
1, CD36, and E-selectin)
2) mimotropes alter T cell behavior
3) cytokine production (TNF, IFN-gamma, IL-1) decrease parsitic specific immune response
Clinical findings and organ system involvement
Hepatocyte injury (jaundice synthetic, and metabolic dysfunction), Renal failure, acidosis, hypoglycemia, hyponatremia, CNS injury (p. falciparum) Blackwater fever
Prevention and treatment of malaria
Prophylaxis- quinolones (chloroquine, mefloquine, primaquine), antifols and sulfas (pyrimethamine, trimethoprim), artemisinins,doxycyclin
Pathophysiology of malaria
Infected RBC–> decrease in HB–> increase in rbc destruction–> cytokine release–> SIRS–> decreased red blood cell production–> endothelial dysfunction–> lose liquid–> DIC (clotting)–> capillary leak syndrome–> splenomegaly+hepatic+renal dysfunction
Toxiplasmosis life cycle
Dormant cysts (bradyzoites) are consumed by wild animals and release tachyzoites (lytic active form), oocytes secreted in cat feces infect via the fecal-oral route then release sporozoites which turn into tachyzoites which replicate in skeletal muscle and brain Cysts are resistant to many things
Toxaplasmosis clinical features
CNS infection, lymphadenopathy, pneumonia, rash, encephalitis, Parkinson’s
or Torch symptoms from transplacental transmission
Fungal virulence factors
Thermotolerance- the more adaptible a bacteria is to growing in colder body temp. from the soil the better ex. Crytococcus neoformans
Enzymes- proteases, lipases, phosholipases to break through mucous membranes or epithelium
Cell wall- sugars are immunogenic but are difficult to clear
Differences between fungal and mammalian eukaryotic cells
ergosterol vs cholesterol, cell wall with glucans, chitin, and cellulose
Antifungal agents
Polyenes (amphotericin B)- binds ergosterol, destabilizes the fungal cell membrane, no resistant
Azole- inhibit fungal cytochrome p450 to interupt ergosterol synthesis, but hurts human p450 so there are a lot of drug interactions
Flucytosine (5-FC)- permease that enters fungal cell and is converted into 5-fluorouracil to disrupt genome
Echinocandins- impair cell wall via 1,3 beta glucan
Griseofulvin- targets microtububles/keratins (hair/nails), inhibits mitosis
Importance of appropriate specimen collection for infections disease testing
contamination which will affect hospital stay, antibiotic use, additional tests, and hopsital bill
Factors affecting turnaround time for microbiological assays
type of assay: blood culture, serological assay, susceptibility to antibiotics, rapid antigen detection, PCR, biochemical profile
type of organism being tested for
Molecular methods of diagnosis
Advantages vs disadvantages
PCR and probe hybridization
Advantages- short turnaround time
Disadvantage- Do not detect more true positives than Gram stain, No impact on therapy for true positives, False positives resulted increased costs, hospital stay, and no clinical benefits
Protein structure of Ab
5 isotypes of Ig’s (M/D/G/E/A), heterotetramer with 2 identical heavy and light chains
Heavy has variable (N-terminal) and constant regions; CDR regions of variable regions is the antigen-binding site
Light has variable regions
Membrane-bound or secreted
Protein structure of TCR’s
Dimer with alpha and beta chains, variable and constant regions with variable region where the antigen binds
Always membrane bound
Mech. of diversity in antigen binding sites
VDJ recombination in heavy chains; VJ recombination in light chains
Junctional diversity- N region addition, P region diversification
Isotype switching (changing constant region)
Somatic hypermutation
