Β-lactamases

Background

Classification

• Classes A, B, and C: serine β-lactamases
  • Class A: inhibited by clavulanic acid or tazobactam
    • Constitutively expressed plasmid
    • Most common ESBL in Gram-negative bacteria
    • Resistance to 2nd and 3rd generation cephalosporins
    • Common in E. coli, Klebsiella, and Proteus spp.
    • Examples include:
      • Penicillinases: TEM-1 (common in GNBs), SHV-1
      • ESBLs: CTX-M, TEM-3
      • Carbapenemases: K. pneumoniae carbapenemase (KPC)
  • Class C: not inhibited by clavulanic acid or EDTA, resistant to cefoxitin, inhibited by clox in vitro
    • AmpC = chromosomal
    • Often an inducible AmpC gene present in the genome
    • Common in Citrobacter, Serratia, and Enterobacter
  • Class D: not inhibited by EDTA, variably inhibited by clavulanic acid; hard to identify
    • Common in Pseudomonas
    • Difficult to detect with routine screening
    • Examples include:
      • ESBLs: OXA-11
      • Carbapenemases: OXA-23, OXA-48
• Class B: metallo-β-lactamase, inhibited by EDTA, not inhibited by clavulanic acid
  • Examples include:
    • Carbapenemases:
      • New Delhi metallo-beta-lactamase (NDM-1)
      • Imipenemases (IMP)
      • Verona integron-encoded metallo-β-lactamases (VIM)

Epidemiology

• The most common β-lactamase is TEM-1
• The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases

Management

• Antibiotic therapy tailored to the resistance pattern
• Carbapenems, aminoglycosides, fluoroquinolones, and TMP-SMX typically work well