Resistance mechanism in GNB: A Basic Overview

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General principles

  1. Beta lactams are strong inducers generally except
    – 3rd and 4th gen cephalosporin
    – Aztreonam
    – Ticarcillin, piperacillin
  2. beta lactamase inhibitors are also strong inducers (clavulanic acid the strongest).
  3. Carbapenems are strong inducers but are stable. So does cefepime (carbapenem > cefepime)
  4. Other strong inducers are generally labile. most of the weak inducers are labile.

Weak and labile inducers (= not stable, easily hydrolyzed) will lead to selection of derepressed AmpC strains.

ESBL producing organisms: SPICE-M

  • Serratia
  • Providentia
  • Indole positive proteus**
  • Citbrobacter
  • Enterobacter
  • Morganella

Inducible ampC producing organisms (ESPCM) – normally present in low levels (repressed), so inducible isnt so significant, but derepressed strains are !

  • Enterobacter spp (E.aerogenes, cloacae)
  • Serratia spp
  • P.aeruginosa
  • Morganella morganii
  • Providencia rettgeri
  • Citrobacter freundii

Basal = not inducible and expressed at low levels: E.coli, shigellae

Summary:

  • ESBL: carbapenems are first line. BL/BLI maybe options if low MIC
  • AmpC
    – Wild inducible type: BL/BLI, normally not clinically significant
    – Derepressed type: carbapenems are first line, but cefepime is okay if susceptible and source control is done.