Enterobacter species

MICROBIOLOGY

  • Gram-negative, aerobic, motile bacilli of the Enterobacteriaceae family that ferments lactose and forms mucoid colonies. Twenty-two species belong to the Enterobacter genus.[11]Enterobacter spp. are commensals of the human gut and are commonly found in water, sewage, and soil.
  • Opportunistic human pathogens include E. cloacae (most common), E. aerogenes (renamed Klebsiella aerogenes), E. gergoviae[20] , and Pantoea agglomerans.
    • E. sakazakii is now classified as Cronobacter.[13]
  • High levels of drug resistance are often seen and are due to:
    • AmpC β-lactamases - Ambler class C
      • Chromosomal AmpC β-lactamases can be constitutive (always active) or inducible (variably active) and are not inhibited by β-lactam β-lactamase inhibitors.
        • Enterobacter spp. have intrinsic resistance to ampicillin, amoxicillin, first-generation cephalosporins, and cefoxitin due to expression of constituitive AmpC β-lactamase.[11]
        • β-lactams must be present to activate inducible β-lactamases, so initial susceptibility reports may not detect resistance that can emerge during therapy. In the absence of β-lactams, AmpR, a regulatory protein, reduces or represses AmpC β-lactamase expression to very low levels.[12]
        • Certain β-lactams induce the production of cell wall degradation products and decrease AmpR repression of AmpC, which results in increased ampC transcription and AmpC expression.
          • ’Potent inducers’ of AmpC production include aminopenicillins, amoxicillin-clavulanate, narrow-spectrum cephalosporins, and cephamycins. AmpC producers, such as E. cloacae, can hydrolyze these agents and are intrinsically resistant.[12]
            • Imipenem is a potent inducer but remains stable against hydrolysis due to forming an acyl-enzyme complex.
          • ’Weak inducers’ of AmpC production include piperacillin-tazobactam, aztreonam, and extended-spectrum cephalosporins, and these antibiotics can be hydrolyzed to a variable extent depending on the amount of β-lactamase production. This results in increased drug-specific MICs.[12]
            • Cefepime is a weak inducer and can withstand hydrolysis by AmpC β-lactamases due to forming a stable acyl-enzyme complex.
      • Plasmid-mediated
        • Phenotypic assays cannot 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 blaCTX-M, blaSHV, and blaTEM. Commercially available molecular platforms limited to detection blaCTX-M.
      • Most often, such organisms demonstrate elevated MICs to cefepime.
      • ESBLs inactivate most penicillins, cephalosporins, and aztreonam.[1]
    • Carbapenemases[16]
      • Ambler class A - Most common are Klebsiella pneumoniae carbapenemases (KPC) that any Enterobacterales can produce.
      • 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
    • The presence of efflux pumps that move β-lactams out of the cell

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Last updated: February 10, 2024