Antimicrobial Resistance

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Antimicrobial Resistance
2011-01-12 16:32:47
Antimicrobial Resistance

Antimicrobial resistance
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  1. List 3 factors that have contributed to the emergence of antimicrobial resistance
    • 1. inappropriate antibiotic use by clinicians
    • 2. lack of patient education or ineffective education
    • 3. Widespread antimicrobial use in the food production industry
  2. Discuss the differences between primary and secondary resistance
    Primary resistance: naturally occurring, prior antimicrobial exposure not required, predictable, also known as inherent, intrinsic, or native resistance

    Secondary resistance: develops following antimicrobial exposure, is not predictable, also known as acquired resistance
  3. What is the example of primary resistance used in class?
    E. coli to vancomycin
  4. How are resistant subpopulations selected in secondary resistance?
    • A population of bacteria is comprised of isolates with varying MICs.
    • Those with low MICs are easily killed.
    • Resistant subpopulations remain and grow.
  5. name 2 types of genetic alterations that may confer secondary resistance
    • spontaneous mutations (point mutations)
    • acquisition of new genetic material
  6. How might a bacteria acquire new genetic material (3 ways)?
    • Conjugation
    • Transduction
    • Transformation
  7. Define conjugation
    transfer of genetic material between bacteria that are in cellular contact with each other
  8. Define Transduction
    transfer of genetic material via a bacteriophage (virus)
  9. Define transformation
    uptake and incorporation of exogenous DNA
  10. What are two types of mediated resistance?
    • Plasmid-mediated resistance - extrachromosomal double-stranded DNA, self-replicating, intra- or inter- species transfer of DNA, autonomous
    • Transposon-mediated resistance ("jumping genes") - DNA fragments, relies on host bacteria or plasmids for replication, intra- or inter- species
  11. Name 3 commonly expressed mechanisms of resistance
    • 1. Antibiotic inactivating enzymes
    • 2. Alteration of the antimicrobial target or active site
    • 3. Alterations in bacterial cellular membranes
  12. Are beta-lactamases produced by G+ or G- microorganisms?
    many of both
  13. How do beta-lactamases work?
    they inactivate beta-lactam antibiotics by splitting the amide bond of the B-lactam ring
  14. Is production of B-lactamases constitutive or inducible?
    Can be either
  15. Examples of microorganisms with inducible B-lactamases
    • Enterobacter spp
    • Citrobacter freundii
    • Serratia marcescens
    • Pseudomonas aeruginosa
  16. Agents that are potent inducers of B-lactamases
    • cefotaxime
    • ceftriaxone
    • ceftazidime
    • imipenem
    • clavulanate
  17. What are ESBLs and what are they active against?
    • Extended-spectrum Beta-lactamases
    • Active vs. all B-lactams except cephamycins (cefotatan, cefoxitin), cefepime, and carbapenems
  18. In which bacteria are ESBLs most commonly found?
    • K. pneumoniae
    • E. coli
  19. Where are bacterial ESBL genes located?
    On plasmids
  20. What are AmpC-type Beta-lactamases active against?
    All B-lactams except cefepime and carbapenems
  21. Which type of Beta-lactamases are not inhibited by B-lactamase inhibitors?
    AmpC-type Beta-lactamases
  22. In which bacteria are AmpC-type Beta-lactamases usually found?
    • K. pneumoniae
    • Enterobacter spp
    • C. freundii
    • M. morganii
    • S. marcescens
    • P. aeruginosa
  23. Where are bacterial AmpC-type Beta-lactamase genes located?
    • plasmids
    • chromosomes
    • (expression may be inducible)
  24. 2 strategies to overcome beta-lactamase mediated resistance
    • administer large doses of B-lactams to overwhelm the B-lactamases
    • combine B-lactams with B-lactamase inhibitors such as tazobactam, clavulanate, and sulbactam
  25. Name 4 types of antibiotic inactivating enzymes
    • beta-lactamases
    • aminoglycoside resistance modifying enzymes
    • chloramphenicol acetyltransferase
    • erythromycin esterase
  26. At what point do aminoglycoside resistance modifying enzymes work?
    as the aminoglycoside is transported across the cell wall of the microorganism
  27. In which microorganisms are aminoglycoside resistance modifying enzymes commonly observed?
    enterococci exhibiting high-level aminoglycoside resistance
  28. 4 ways the antimicrobial target or active site can be altered to confer resistance (with an example of each)
    • Penicillin-binding proteins (e.g. Staph aureus resistance to B-lactams)
    • Ribosomal binding sites (e.g. Streptococcal resistance to gentamicin)
    • Cell wall precursors (e.g. enterococcal resistance to vancomycin
    • DNA gyrase (e.g. P. aeruginosa resistance to ciprofloxacin)
  29. 3 ways bacterial cellular membranes can be altered to give resistance
    • Porin channels
    • Transport proteins
    • Efflux pumps
  30. What are porin channels and how do they work for bacterial resistance?
    • portals through the bacterial cell wall
    • aqueous interior
    • facilitate transport of hydrophilic molecules into the cell
    • change in the size or number of porin channels may confer resistance
  31. How do efflux pumps work?
    They are proteins that actively pump the agent out of the bacteria
  32. What antibiotics are removed by the efflux pumps of E. coli, S. aureus, P. aeruginosa, S. pneumoniae, N. gonorrhoeae, and Candida spp?
    • E. coli - TCs and FQs
    • S. aureus - TCs and FQs
    • P. aeruginosa - FQs
    • S. pneumoniae - macrolides
    • N. gonorrhoeae - TCs
    • Candida spp - azoles
  33. What is MRSA's resistance secondary to?
    the production of an altered PBP
  34. How is resistance transferred in MRSA?
    via plasmids or transposons
  35. What is the treatment of choice for MRSA?
  36. While the DOC for MRSA is vanco, what meds might other strains be sensitive to? What others may also be used?
    • some strains may be sensitive to TMP/SMX
    • may also use linezolid and daptomycin
  37. What is VISA and what might it be due to?
    • Vancomycin intermediate susceptibility (isolate of MRSA)
    • May be due to alterations in the cell wall and altered autolytic expression
  38. What may be a treatment option for VISA?
  39. What about VRSA isolates suggests transfer of resistance determinants from enterococci rather than just a point mutation?
    they had mecA and vanA genes
  40. What common community-acquired infections does S. pneumoniae cause?
    • otitis media
    • pneumonia
    • sinusitis
  41. From what patients are penicillin-resistant isolates of S. pneumoniae commonly isolated?
    children < 6 years of age
  42. In addition to becoming resistant to penicillins, what other agents is S. pneumoniae developing resistance to? What genes encode for this?
    • cephs, macrolides, TMP/SMX, TCs
    • mosaic genes
  43. What gives S. pneumoniae resistance to penicillin?
    modified PBPs
  44. Does antimicrobial resistance in vitro translate to clinical resistance?
    not necessarily
  45. Does a high-level of penicillin resistance in pneumococci mean that penicillin will not work in pneumonia?
    No. It has not been clearly associated with PCN failure.
  46. Is enterococcus an increasingly common nosocomial or community-acquired pathogen?
  47. What antimicrobials are enterococcus intrinsically resistant to?
    • TMP/SMX
    • cephalosporins
  48. What must therapy be combined with for a cidal effect upon enterococci?
  49. What is acquired resistance of enterococci to penicillins due to?
    alterations in PBPs
  50. What negates synergy in enterococcus?
    high-level aminoglycoside resistance is conferred by production of aminoglycoside modifying enzymes
  51. What is vanco-resistance in enterococcus secondary to?
    alterations in the D-ala-D-ala linkages in cell wall precursors
  52. Name 3 distince genomic variants that are responsible for the expression of vanco resistance in enterococci
    • Van A - inducible
    • Van B - inducible
    • Van C - constitutive
  53. Enterococcus treatment strategies
    • vanco, linezolid, daptomycin, and streptogramins
    • intermittent vs. continuous infusions of B-lactams and vanco
    • traditional vs. once-daily dosing of aminoglycosides
  54. 6 strategies to prevent the spread of antibiotic resistance
    • patient education
    • knowledge of local susceptibility patterns
    • prescriber education
    • develop guidelines for appropriate antimicrobial usage
    • vaccination
    • hand washing