Mechanisms of Resistance

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The page below is a sample from the LabCE course Drug-Resistant Superbugs, Multi-drug Resistant Organisms: MRSA, VRE, Clostridioides difficile, and CRE. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

Learn more about Drug-Resistant Superbugs, Multi-drug Resistant Organisms: MRSA, VRE, Clostridioides difficile, and CRE (online CE course)
Mechanisms of Resistance

Members of the Enterobacterales order demonstrate intrinsic patterns of resistance to certain antimicrobial agents. Resistance to additional antibiotics is achieved through multiple, acquired resistance mechanisms, including:
  • Extended-spectrum beta-lactamases (ESBLs) - A diverse, complex, and rapidly evolving group of plasmid-mediated enzymes that hydrolyze penicillins, cephalosporins, and aztreonam.
  • AmpC beta-lactamases - Cephalosporinases that are chromosomally- or plasmid-mediated enzymes (inducible in some organisms) that mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and beta-lactamase inhibitor/beta-lactam combinations.
This course will focus on the very serious resistance mechanism emerging in the Enterobacterales order, referred to as carbapenemase resistance. Carbapenemases are diverse enzymes that vary in their ability to hydrolyze carbapenems and other beta-lactams. Among Enterobacterales there are several circumstances that can result in carbapenem resistance:
  1. Carbapenemase production (examples include Klebsiella pneumoniae carbapenemase [KPC], New Delhi Metallo-beta-lactamase [NDM], Verona Integron-Encoded Metallo-beta-lactamase [VIM], Imipenemase [IMP], and Oxacillinase-48 [OXA-48]).
  2. Non-carbapenemase-producing CRE. Combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms (eg, cephalosporinase or ESBL combined with porin loss which limits entry of carbapenem into the cell and can render an organism nonsusceptible).
  3. Harboring carbapenemase genes - evident in the usually elevated MICs to imipenem (eg, Morganella morganii, Proteus species, and Providencia species)