AmpC β-lactamase

Background

• Class C serine β-lactamase produced by many Enterobacterales and afermentative Gram-negative bacilli
• Production of the β-lactamase may be from:
  • Inducible chromosomal resistance, often following a few doses of ceftriaxone or ceftazidime
  • Stable chromosomal de-repression, often seen in Escherichia coli and Shigella
  • Plasmid-mediated ampC genes, including bla_CMY, bla_FOX, bla_DHA, bla_ACT, and bla_MIR, and is seen in Escherichia coli, Klebsiella pneumoniae, and Salmonella
• Chromosomal de-repression and plasmid-mediated expression are both generally constitutively expressed, so treatment may be guided by initial susceptibility testing

Inducible AmpC

• Bacteria with moderate to high risk of clinically-significant AmpC production includes:
  • Enterobacter cloacae
  • Klebsiella aerogenes
  • Citrobacter freundii
• The above three species have inducible AmpC in up to 40% of isolates
• Not necessarily all of the SPICE organisms have risk of inducible AmpC production, of which only about 5% of isolates will have an inducible AmpC
• Antibiotics that are the best inducers include aminopenicillins (amoxicillin and ampicillin), first-generation cephalosporins, and cephamycins
  • Also imipenem, though it remains effective even after induction of AmpC overexpression
• Antibiotics that are weaker inducers include piperacillin, ceftriaxone, ceftazidime, cefepime, and aztreonam