ID: Gram negative resistance

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ID: Gram negative resistance
2011-03-10 19:22:57
ID Gram negative resistance

ID: Gram negative resistance
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  1. risk factors for GN resistance?
    • age >65
    • previous abx exposure
    • hosp admission >2 or more days in preceding 90d
    • residence NH, ECF
    • fecal incontinence
    • indwelling catheter
    • mechanic vetilation
    • tube feed
    • hepatic failiure and long term HD
  2. ceftriaxone not working for pseudo is what kind of resistance? innate vs. developing
  3. cefepime not working for pseudo is what kind of resistance? innate vs. developing
  4. notorious resistant bugs? - ESKAPE
    • GP: E.faecium, S.aureus
    • GN: K.pneumo, A.baumanni, P. aeru, Enterobacter spp
  5. ESBL producing bacteria are?
    e.coli, klebsiella
  6. which cephalo induces ESBL producing bacteria?
    3rd gen cephalo
  7. definition of MDR?
    • resistant to equal to or > 3 of the following classes:
    • B lactam (cephalo, monobact, pcn, carba)
    • FQ
    • AG
  8. definition of pan-resistant?
    resistant to ALL avail abx options
  9. 4 mechanisms of GN resistance
    • production of enzyme (destroy integrity of abx)
    • mutation at binding site (abx can't bind)
    • down regulate outer membrane protein (abx can't get into periplasmic space)
    • efflux pump (remove out abx)
  10. if bacteria produce enzyme to resist abx, what can you use?
    suicide substrate sulbactam can overcome!
  11. mechanism of resistance of p.seudo?
    • mechanism #3: down regulate outer membrane protein (prevent abx from getting into periplasmic space); reduced permeability
    • mechanism #4: efflux pump
  12. mechanism of resistance of imipenem?
    • loss of 54-kD outer membrane protein (OprD)
    • (mechanism #3) down regulate outer membrane protein (prevent abx from getting into periplasmic space) reduced permeability
  13. which is better vs. bacteria resistance and why? imi vs. mero
    • imi doesn't work once OprD is lost (54kD outer membrane protein)
    • mero needs two steps (upregulation of MexAB-OprM efflux pump AND OprD loss)
  14. mechanism of resistance of acinetobacter?
    • mech #4: efflux pump
    • need double cover abx
  15. mech of resistance of FQ?
    • mech #2: binding site mutation
    • mutation of topoisomerase II (gyrA) and IV (parC)
    • this results in increase MIC
    • (gyrA mutation is most impt and occurs before parC mutation)
  16. mech of resistance of AG? which is the weakest AG?
    • mech #1: production of enzyme
    • 3 enzymes: acetyl-, adenyl-, and phophoryl-transferases
    • 1) they chemically modify AG structure
    • 2) interfere with drug transport
    • 3) prevent AG from binding to 30S rib subunit
    • gent usu goes down first, then amik and tobra
  17. most common and clincially sig resisstance mechanism displayed by ALL GN bacilli?
    production of b-lactamase
  18. how to b-lactamase work?
    hydrolyze the b-lactam chem structure and inactivate the drug
  19. 4 categories of b-lactamases (bush-jacoby medeiros classification)
    • 1) cephalosporinase
    • 2a) ESBL
    • 2b) cerbapenemase
    • 3) metallo-b-lactamase
  20. examples of ESBL (2a)? what do these do? how are they inhibited
    • TEM-10
    • SHV-2
    • CTX-M
    • they hydrolyze ESC
    • (chromosomally encoded or plasmid and transposon mediated)
    • inhibited by clavulanate
  21. 2 major machanism of resistance for ESBL (2a)?
    • selection of point mutant of TEM and SHV type plasmid-mediated b-lactamses
    • genes encoding CTX-M type enzymes thru horizontal gene transfer (CTX-M 15 is globally dominant strain)
  22. how to you test ESBL resistance (2a)?
    • ceftazidime MIC >2ug/ml
    • confirmed if MIC changes upon clavulanic acid addition
  23. to what abx is ESBL resistance (2a) resistant to? where is resistant mechanism carried on?
    • all cephalo (except cefoxitin and cefotetan - cephamycin)
    • pcn (except zosyn)
    • aztreonam
    • also FQ, bactrim, AG
    • mech carried on plasmid
  24. DOC for ESBL (2a) treatment (e.coli and kleb)?
    • imi, mero!
    • alt: erta, tige, AG, FQ (only for UTI)
  25. can AmpC cephalosporinase (1) be inhibited by b-lactamase inhibitors, like clavulanic acid and tazobact?
  26. what b-lactamase resistance does klebsiella have?
    • AmpC cephalosporinase (1)
    • ESBL (2a)
    • carbapenemase (2b)
  27. what b-lactamase resistance does e.coli have?
    ESBL (2a)
  28. to what abx is AmpC-cephalosporinase (1) resistant to?
    • all cephalo!!! (including cefoxitin, cefotetan - cephamycin)
    • also zosyn as well
  29. what is the DOC and alt tx for AmpC-cephalosporinase (1) bugs?
    • DOC: cefepime!
    • imi, mero
  30. action of AmpC cephalosporinase (1)?
    loss of outer membrane porins and/or over expression of efflux pump
  31. action of carbapenemase (2b)?
    • hydrolyze carbapenem and other b-lactam abx
    • basically ESBL resistance + carba
  32. klebsiella with carbapenemase (2b) resistance. what to use?
    • tige
    • polymixin
    • AG(?)
  33. pseudo with carbapenemase (2b) resistance. what to use?
    • polymixin
    • AG
    • (cannot use tige unlike klebsiella b/c innate resistance)
  34. Acinetobacter with carbapenease (2b) resistance. what to use?
    • tige
    • polymixin
    • amipicillin/sulbact
    • AG
    • (highlighted = DOC)
  35. examples of carbapenemase (2b)?
    • KPC
    • SME
  36. examples of metallo-b-lactamase (3) ?
    • IMR1
    • VIM1
    • SPM1
  37. what b-lactamase resistance does pseudomonas have?
    • carbapenemase (2b)
    • metallo-b-lactamase (3)
  38. what b-lactamase resistance does acinetobacter have?
    • innate cephalosporinase AmpC (1)
    • ESBL (2a)
    • metallo-b-lactamase (3)
    • mutation in topoisomerase, AG modifying enzyme, reduced expression of outer membrane protein, efflux
  39. 3 organisms that have metallo-b-lactamase as resistance?
    • pseudo
    • enterobactericiae
    • acinetobacter
  40. metallo-b-lactamase (3) is resistant to? this mechanism is carried on?
    • carba
    • ceftazidime, cefepime
    • zosyn
    • carried on integron (easily transferable)
  41. metallo-b-lactamase (3) is sensitive to which abx?
    • tige
    • polymixin
    • aztreonam (for pseudo)
  42. when you have ESBL, which abx class is most reliable?
    carbapenem (slide 34)
  43. which conditions/abx can fail to achieve PD target?
    • FQ
    • under dose (thus use high dose AG)
    • slide 35
  44. 4 agents in which the MICs of drug increase up to 100 fold due to ESBL?
    • cefotaxime
    • ceftriaxone
    • cefepime
    • zosyn
  45. 3 reasons for increased mortality in ESBL?
    • more serious or deep seated enterobacter spp infxn
    • higher organism burden
    • inadequate or delayed abx tx
  46. what is NDM-1?
    what abx can tx this?
    • new delhi metallo-b-lactamase
    • presence of carbapenem resistant gene
    • colistin, tige, maybe aztreonam
  47. SE issue with imipenem/cilastatin?
    • seizure
    • (careful with dose)
  48. which has more activity vs. pseudo?
    a) imi
    b) mero
    c) erta
    d) dori
    mero and dori
  49. which has more activity vs. acinetobacter?
    a) imi
    b) mero
    c) erta
    d) dori
  50. which has no activity vs. pseudo nor acinetobacter?
    a) imi
    b) mero
    c) erta
    d) dori
  51. which binds stronger to ribosome? tetracycline vs. tigecycline
    tige binds 5x more
  52. is tigecycline active vs. metallo-b-lactamase producing kleb and e.coli?
  53. is tigecycline active vs. ESBL producing kleb and e.coli?
  54. is tigecycline active vs. KPC producing kleb and e.coli?
    • yes
    • but little data
  55. is tigecycline active vs. acinetobacter?
    only in vitro activity so cannot tell if S, I or R
  56. which conditions is tige indicated?
    • cSSTI
    • IA (anaerobe, GN, MRSA)
    • CAP +/- bacteremia (but doesn't stay in blood long)
  57. is tige active vs. pseudo?
  58. is tige active vs. providencia
  59. is tige active vs. morganella?
  60. is tige active vs. proteus?
  61. does tigecycline have high urine concentration?
    • nope, rapidly moves into tissues thus not in urine and blood (slide 44)
    • you can inc urinary conc of tige by using high dose (slide 48)
  62. for VAP tx, which is better, carba vs. tige? (slide 44)
  63. enterobactericiae is sensitive vs.? (put in order) slide 49
    • tige
    • polymixin B
    • amik
  64. colistin is aka ___
    polymixin E (slide 50)
  65. polymixin is __ depedent and is it cidal or static?
    • conc dependent
    • cidal
  66. actions of polymixin?
    • bind phospholipid in the outer membrane of GN
    • cell wall destabilize and cell death
  67. is polymixin active vs. p.aeru?
  68. is polymixin active vs. acinetobacter?
  69. is polymixin active vs. k.pneumo?
  70. is polymixin active vs. e.coli (MDR)?
  71. is polymixin active vs. proteus?
  72. is polymixin active vs. providencia?
  73. is polymixin active vs. burkholderia?
  74. is polymixin active vs. nesseria or serratia?
  75. SE of polymixin? which has less SE (polymixin B vs. E)
    • nephro and neuro tox
    • colistin (E) has less
  76. what to use to tx peritonitis with k.pneumoniae (ESBL)?
    polymix B + amik + mero
  77. does sulbactam have activity vs. acinetobacter?
  78. how to tx severely ill pseudo empirically?
    • combo therapy!
    • zosyn or ceftazidime + cipro or AG
    • (b-lactam + AG)
  79. which is better to use for kleb pneumo?
    carba mono vs. carba + polymix
    • carba + polymix
    • lower mortality
  80. for KPC (2b), which is better?
    polymix mono vs. AG+ polymix+ tige
    combo is better
  81. what's ME 1036?
    what bug does it cover, not cover?
    • IV carba (phase I)
    • covers MRSA, VRE, ESBL e.coli and kleb
    • NO pseudo
  82. what's PZ-60? what bugs does it cover?
    • IV carba
    • good vs. MRSA and GN
    • no pseudo and acineto
  83. what's sulopenem?
    active vs. which bug?
    • IV and PO penem
    • good vs. ESBL enterobact, GP, anaerobe
  84. what's tomopenem? active vs. which bug?
    • carbapenem
    • active vs. p.aeru
    • cSSTI, HAP
  85. what's PTK-0796? what spectrum does it have?
    • IV and po aminomethylcycline
    • active vs. MRSA, VRE, some resistant GN patho (acineto)
  86. what do metallo b-lactamase inhibit ME1071 (CP 3242) med cover?
    pseudo and acineto
  87. what's BAL 30376?
    • b-lactam b-lactamase inhibitor
    • acineto
    • pseudo
    • b lactamase enterobacteriaceae
  88. what does "squeezing the balloon phenomenon" mean?
    • antibiotic rotation
    • may develop resistance elsewhere
    • not good
  89. how to prevent GN resistance? what abx to use?
    • bactrim
    • cipro
    • third gen cephalo
    • AG
  90. acinetobacter surprives long time on surfaces. what can you do for ICU pts?
    chlorhexidine skin disinfection to reduce skin contamination