Which genes confer resistance to extended-spectrum β-lactamases (ESBLs) and carbapenems?

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Last updated: November 1, 2026 • View editorial policy

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Genes Conferring Resistance to ESBLs and Carbapenems

The key genes conferring ESBL resistance are blaCTX-M, blaTEM, blaSHV, and blaOXA-1, while carbapenem resistance is primarily mediated by Class A carbapenemases (KPC), Class B metallo-β-lactamases (NDM, VIM, IMP), and Class D carbapenemases (OXA-48-like and OXA-23/58 types). 1

ESBL Resistance Genes

The extended-spectrum β-lactamase phenotype is encoded by plasmid-mediated genes that confer resistance to cephalosporins and aztreonam while maintaining susceptibility to carbapenems 2:

  • blaCTX-M family: The most prevalent ESBL gene globally, with blaCTX-M-15 being particularly common 3, 4, 5
  • blaTEM: Frequently detected alongside other ESBL genes, often carried on plasmids with multiple resistance determinants 2, 3
  • blaSHV: Common in Klebsiella species, often co-carried with other resistance genes 3
  • blaOXA-1: Less common but increasingly recognized in ESBL-producing isolates 3

Important caveat: Plasmids encoding ESBLs frequently carry resistance genes to aminoglycosides and other drug classes, creating multidrug-resistant phenotypes even though ESBL-producing strains typically remain carbapenem-susceptible 2.

Carbapenem Resistance Genes

According to the Ambler classification system, carbapenemases fall into three main classes 1:

Class A Carbapenemases (Serine β-lactamases)

  • blaKPC (Klebsiella pneumoniae carbapenemase): The most common carbapenemase globally, accounting for 47.4% of carbapenem-resistant Enterobacterales 1
  • Susceptible to newer β-lactam/β-lactamase inhibitor combinations like ceftazidime/avibactam and meropenem/vaborbactam

Class B Metallo-β-lactamases (MBLs)

  • blaNDM (New Delhi metallo-β-lactamase): Increasingly prevalent worldwide, accounting for approximately 20.6% of carbapenem resistance 1
  • blaVIM: Common in Pseudomonas aeruginosa and other gram-negatives 1, 6
  • blaIMP: First identified in Japan (IMP-1 in 1991), now globally distributed 2, 5

Critical distinction: MBLs hydrolyze all β-lactams EXCEPT aztreonam, and are NOT inhibited by classic serine β-lactamase inhibitors 1. This makes them particularly worrisome clinically.

Class D Carbapenemases (Oxacillinases)

  • blaOXA-48-like: Accounts for approximately 19% of carbapenem resistance in Enterobacterales 1
  • blaOXA-23 and blaOXA-58: Predominant in Acinetobacter baumannii, causing increasing carbapenem resistance 2, 6

Alternative Resistance Mechanisms

Beyond carbapenemase production, carbapenem resistance can occur through 2, 1:

  • Porin loss: Decreased expression of outer membrane porins (e.g., OprD in Pseudomonas aeruginosa) causes carbapenem resistance without carbapenemase production
  • AmpC hyperexpression: Chromosomal AmpC β-lactamases in Enterobacter, Citrobacter, and Serratia species, when combined with porin loss, can confer carbapenem resistance
  • Efflux pumps: Multiple efflux systems in Pseudomonas aeruginosa contribute to intrinsic and acquired resistance

Methicillin Resistance in Staphylococcus aureus

While not a β-lactamase gene, mecA encodes altered penicillin-binding protein 2a (PBP2a) with reduced affinity for all β-lactams, carried on mobile genetic elements 2. This confers resistance to all commercially available β-lactams.

Clinical Implications

Rapid identification of specific carbapenemase families (KPC, NDM, VIM, OXA-48-like) is strongly recommended because each class confers different susceptibility profiles requiring distinct treatment strategies 1. For example, KPC-producing organisms respond to ceftazidime/avibactam, while MBL-producers require alternative approaches such as aztreonam-based combinations.

The co-occurrence of ESBL and carbapenemase genes on the same plasmid is increasingly common, creating extensively drug-resistant phenotypes 1, 4. This emphasizes the importance of molecular characterization beyond phenotypic testing alone.

References

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