Antibiotic Resistance Mechanisms in Enterobacteriaceae

Enterobacteriaceae encompass a diverse family of Gram-negative bacteria that include common pathogens such as Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. Resistance in these organisms arises principally through enzymatic inactivation of β-lactam antibiotics via chromosomal or plasmid-encoded β-lactamases (including AmpC, extended-spectrum β-lactamases and carbapenemases), modification of antibiotic targets (for example alterations in penicillin-binding proteins), reduced drug uptake through porin loss or mutation and active efflux. AmpC β-lactamases can be inducibly expressed in response to antibiotic exposure, with stable high-level “de-repression” resulting from mutational inactivation of regulatory elements. Plasmid-mediated transfer of resistance determinants accelerates global dissemination, often co-assembling with genes conferring resistance to aminoglycosides and fluoroquinolones. The cumulative effect of these mechanisms has contributed to rising rates of healthcare-associated and community infections that challenge empirical therapy and drive the development of novel β-lactamase inhibitors, rapid diagnostics and stewardship strategies.

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Antibiotic Resistance Mechanisms in Enterobacteriaceae publication trend

The graph below shows the total number of articles in antibiotic resistance mechanisms in enterobacteriaceae across all publications each year (not limited to Nature Index journals).

Technical terms

AmpC β-lactamase: A class C enzyme that hydrolyses cephamycins and broad-spectrum cephalosporins; expression may be inducible or constitutively elevated via regulatory mutations.

Extended-spectrum β-lactamase (ESBL): Enzymes that confer resistance to third-generation cephalosporins and monobactams; often plasmid-mediated and inhibited by clavulanic acid.

Carbapenemase: β-lactamases capable of hydrolysing carbapenems, including KPC, NDM, OXA-48 and VIM types, often associated with high-risk clones.

Inducible resistance: Upregulation of β-lactamase gene expression in response to β-lactam antibiotic exposure, mediated by cell-wall recycling signals and regulatory proteins.

De-repression: Constitutive overexpression of an inducible resistance determinant due to loss-of-function mutations in negative regulators, leading to sustained high-level resistance.

References

1. Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study. Critical Care (2024).
2. Enterobacterales carrying chromosomal AmpC β-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020–2022. International Journal of Antimicrobial Agents (2024).
3. Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections. European Journal of Clinical Microbiology & Infectious Diseases (2023).