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Carbapenemase-producing Enterobacterales (CPE) and the need for change

We are running out of antimicrobial options:1 CPE can hydrolyse many β-lactam antibiotics, rendering them ineffective.2,3

As these bacteria can rapidly spread and colonise patients in healthcare environments, preventing their transmission is a major global initiative.3

 

The problem with CPE has worsened over the past 20 years:4,5
 
  • The increased prescription of carbapenems due to the expansion of extended-spectrum β-lactamases (ESBLs)4
  • A rapid increase of antimicrobial resistance (AMR)4
  • Resulting in reduced therapeutic options to successfully treat infections due to carbapenemase-producing organisms5
However, by understanding and raising awareness of the threat posed by CPE, we can work together and better safeguard our communities.
Examining carbapenem-producing Enterobacterales

The ‘Big Five’ carbapenemases

Globally there are five main carbapenemases of clinical relevance, commonly known as the ‘Big Five’:4.6

  • Imipenemase metallo-β-lactamase (IMP)
  • New Delhi metallo-β-lactamase (NDM)
  • Verona Integron-encoded metallo-β-lactamase (VIM)
  • Klebsiella pneumoniae carbapenemase (KPC)
  • Oxacillinase-48-like carbapenemases (OXA-48-like)


They can be grouped based on their molecular structure through the Ambler classification system.7


Classification of the most relevant carbapenemases produced by Enterobacterales7,8
Ambler-Bush Class Carbapenemase type Common examples Most frequently identified in
A Serine-β-lactamases KPC, Serratia marcescens enzymes (SME), imipenem-hydrolysing β-lactamase (IMI)
K. pneumoniae, S. marcescens and other Enterobacterales
 
B Metallo-β-lactamases
(MBLs)
NDM, VIM, IMP, 
German imipenemase (GIM), and Sao Paulo metallo-β-lactamase (SPM)
E. coli, K. pneumoniae, Enterobacter, and other Enterobacterales
D Serine-β-lactamases OXA-48-like K. pneumoniae, E. coli, and other Enterobacterales

Adapted from: Villegas MV, et al. 2019.8

The production of the five main carbapenemases is of high clinical, therapeutic and epidemiological relevance:8,9

 

  • They cause hospital outbreaks associated with clones and plasmid dissemination
  • Infections caused by carbapenemase-producing bacteria are associated with higher mortality rates and increased patient- and healthcare-associated burden
  • They can lead to multi-resistance and pan-resistance, further complicating treatment decision-making


The emergence of CPE has become a major public health crisis worldwide10
The widespread dissemination of CPE and their ability to mediate carbapenem resistance represents one of the most challenging problems of antimicrobial resistance that we face today.11

Increased awareness and understanding of CRE, including MBLs, OXA-48-like and KPC, along with the administration of timely, appropriate treatment to treat infections can improve patient outcomes.10,12,13

 

It is important to slow the spread of CPE and rising mortality rates

Explore the threat to your patientsClick here to see how CPE is spreading
Learn about their incidence and prevelance in your region
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References
1.
Sader HS, et al. Eur J Clin Microbiol Infect Dis 2022;41:477–87;
2.
Centers for Disease Control and Prevention. CRE technical information. Available at: www.cdc.gov/hai/organisms/cre/technical-info.html#Definition. Published November 2019; accessed March 2024
3. Bonomo RA, et al. Clin Infect Dis 2018;66:1290–7
4.
Henderson J, et al. J Hosp Infect 2020;104(1):12–19
5. Bahr G, et al. Chem Rev 2021;121(13):7957–8094
6. Bonnin RA, et al. Front Med (Lausanne) 2021;7:616490
7. Tooke CL et al. J Mol Biol 2019;431(18):3472–3500
8. Villegas MV, et al. Infection 2019;23:358–68
9. Tamma PD, et al. Clin Infect Dis 2017;64:257–64
10. Pudpong K, et al.
Infect Drug Resist 2022;15:3025–37
11. Sader HS, et al. J Antimicrob Chemother 2021;76:659–66
12.
Papadimitriou-Olivgeris M, et al. Eur J Clin Microbiol Infect Dis 2017;36:1125–31
13. Zavascki AP, et al. J Antimicrob Chemother 2006;58:387–92

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