β-lactam resistance

From IDWiki
Β-lactam resistance /
Revision as of 11:10, 2 April 2022 by Aidan (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)


Mechanisms

  • ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
  • Penicillin binding protein mutations (e.g. MRSA)
  • Efflux pump mutations
  • Porin channel mutations that reduce antibiotic influx

β-lactamases

Ambler Classification of ß-lactamases

  • Based on amino acid sequences rather than function
  • Classes A, C, and D are serine ß-lactamases, while class B are metallo-β-lactamases
Class Binding Site Examples Inhibitors
A serine TEM, SHV, KPC, CTX-M, GES avibactam, vaborbactam, relebactam
B metallo VIM, NDM, IMP
C serine AmpC, P99 avibactam, vaborbactam, relebactam
D serine OXA (oxacillinase) enzymes avibactam (OXA-48)

Specific ß-lactamases

  • TEM-1: most common β-lactamase in Gram-negative bacteria
  • KPC: most common carbapenemase
  • NDM-1: broad-spectrum metallo-β-lactamase and carbapenemase
  • OXA-48: most common carbapenemase in Acinetobacter

Efflux Pumps

  • Major cause of resistance in Pseudomonas aeruginosa and similar species
  • e.g. MexAB-OprM, which confers broad antimicrobial resistance including cephalosporins and some carbapanems

Porin Loss

Management