MICROBIOLOGY

• Gram-negative, aerobic, motile bacilli of the Enterobacteriaceae family. Ferments lactose and forms mucoid colonies. Commonly found in water, sewage, and soil.[8]
• Opportunistic human pathogen includes E. cloacae (most common), E. aerogenes (renamed Klebsiella aerogenes), E. gergoviae[17] and Pantoea agglomerans.
  • E. sakazakii now classified as Cronobacter.[10]
• High levels of drug resistance often seen and due to:
  • AmpC β-lactamases - Ambler class C
    • Chromosomal AmpC can be constitutive (always active) or inducible (variably active) and are not inhibited by β-lactam β-lactamase inhibitors.[19]
      
      • β-lactams must be present for activation of inducible β-lactamases, so initial susceptibility reports may not detect resistance that can emerge during therapy.
    • Plasmid-mediated[9]
      • Phenotypic assays are unable to distinguish between AmpC β-lactamase production due to derepression of chromosomal versus plasmid-associated ampC gene.
  • Plasmid-encoded extended-spectrum β-lactamases (ESBLs)
    • ESBL genes include bla_CTX-M, bla_SHV, and bla_TEM. Commercially available molecular platforms limited to detection bla_CTX-M.
    • Most often such organisms demonstrate elevated MICs to cefepime.
    • ESBLs inactivate most penicillins, cephalosporins, and aztreonam.[1]
  • Carbapenemases[14]
    • Ambler class A - Most common are Klebsiella pneumoniae carbapenemases (KPC) that can be produced by any Enterobactrerales.
    • Ambler class B - Metallo-β-lactamases include: New Delhi (NDMs), Verona integron-encoded (VIM), and imipenem-hydrolyzing (IMPs)
    • Ambler class D - Oxacillinase (OXA-48-like) carbapenemases
• Ceftriaxone MIC ≥ 2 is used as a proxy for ESBL production.
• Other resistance mechanisms
  • Alterations in the active site of penicillin-binding protein
  • Defects in outer membrane permeability that reduce diffusion of β-lactams into the cell
  • Presence of efflux pumps that move β-lactams out of the cell