What are ESKAPE pathogens and why are they important?

When people discuss antimicrobial resistance (AMR), the term ‘ESKAPE pathogens’ can often be used. But what does this term refer to and why is it important in relation to AMR?

ESKAPE pathogens is an expression which refers to six specific groups of bacteria that commonly cause antibiotic-resistant infections and consequently pose a significant threat to global health.

Enterococcus faecium

Staphylococcus aureus

Klebsiella pneumoniae

Acinetobacter baumannii

Pseudomonas aeruginosa

Enterobacter species

These pathogens share properties that enable them to prosper in healthcare settings [1] and “escape” the actions of antibiotics [2].

The ESKAPE pathogens possess multiple characteristics that enable them to avoid the actions of antibiotics. For example, one way that they can evade antibiotic treatment is by inactivating the drug [3]. They do this by producing small molecules known as proteins which can breakdown the antibiotics, causing them to become ineffective. They can also employ proteins known as efflux pumps which sit within the bacteria’s cell wall. These efflux pumps can transport and remove the antibiotic out of the cell, preventing the drug from killing the bacteria [3].

In 2021 it was estimated that the ESKAPE pathogens were responsible for over 680,000 deaths attributable to AMR [4]. What is of great concern is that fact that some of these pathogens are now displaying resistance against last-resort antibiotics [3]. This means that we may not have effective treatments that successfully control infections caused by ESKAPE pathogens.

Last year the World Health Organization published a document called the Bacterial Priority Pathogens List [5]. The aim of this document is to highlight species of bacteria that pose a threat to global health and provide a guide to support the research and development of new therapies [5]. In this report all six ESKAPE pathogens were included [5], signifying the problem that these bacteria pose to society.

So, what are these six groups of bacteria?

Enterococcus faecium

E. faecium is a bacterium typically implicated in bloodstream and urinary tract infections [1]. In the 1980s it was discovered that some E. faecium bacterium were resistant to a type of antibiotic known as vancomycin [6]. It is thought that extensive antibiotic use in hospitals and agricultural settings is responsible for the appearance of this antibiotic-resistant bacterium [6].

Staphylococcus aureus

S. aureus is a bacterium that can be found on our skin and within our noses [7]. Normally it does not cause us any harm, however if it enters the body through for example a graze in the skin it can cause serious illness. One type of S. aureus that presents a major problem is methicillin-resistant S. aureus, which can cause lung and bloodstream infections [8].

Klebsiella pneumoniae

K. pneumoniae is a species of bacterium which causes urinary tract infections and pneumonia [1]; a type of infection which causes the inflammation of the lungs [9]. This species of bacteria has been found to display resistance against various antibiotics such as cephalosporins and carbapenems [3].

Acinetobacter baumannii

A. baumannii is a species of bacteria that causes infections in healthcare and community settings [10]. Concerningly some A. baumannii bacterium have been found to be resistant to all types of antibiotics [10]. It is therefore essential that new treatments are discovered that successfully kill this species of bacteria.

Pseudomonas aeruginosa

P. aeruginosa is estimated to be responsible for 10% of all infections acquired in healthcare settings [3]. It poses a particular problem for individuals who have a condition known as cystic fibrosis; a disease which causes the build-up of thick, dense mucus in organs such as the lungs [11]. P. aeruginosa exhibits resistance against multiple types of antibiotics, enabling it to survive and cause long-term infections [3].

Enterobacter species

Enterobacter species pose a significant threat to preterm babies and patients in intensive care wards [3, 12]. They have been found to display resistance against multiple antibiotics such as ampicillin, cephalosporins and amoxicillin [12] and cause infections including but not limited to abdominal, bloodstream and urinary tract infections [1].

To successfully combat ESKAPE pathogens it is important that we take a multifaceted approach. AMR surveillance, correct antibiotic use, and the development of novel therapeutics such as phage therapy are just some of the ways that we could try to effectively tackle these pathogens moving forward [3].

References

[1] Miller, WR. Arias, CA. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nature Reviews Microbiology. 2024. 22:598-616. https://doi.org/10.1038/s41579-024-01054-w

[2] Zhen, X. Stålsby Lundborg, C. Sun, X. Hu, X. Dong, H. Economic burden of antibiotic resistance in ESKAPE organisms: a systematic review. Antimicrobial Resistance and Infection Control. 2019. 8. https://doi.org/10.1186/s13756-019-0590-7

[3] De Oliveira, DM. Forde, BM. Kidd, TJ. Harris, PNA. Schembri, MA. Beatson, SA et al. Antimicrobial Resistance in ESKAPE Pathogens. Clinical Microbiology Reviews. 2020. 33(3). https://doi.org/10.1128/cmr.00181-19

[4] Institute for Health Metrics and Evaluation. Deaths attributable to bacterial antimicrobial resistance by pathogen. Available at: https://vizhub.healthdata.org/microbe/?settings=eyIxIjoiYW1yIiwiMiI6ImJhciIsIjMiOiJhbXIiLCI0IjoyMiwiNSI6MSwiNiI6MSwiNyI6MSwiOCI6MSwiOSI6MSwiMTIiOjEsIjEzIjoxLCIxNCI6MSwiMTUiOjEsIjE2IjoyLCIxNyI6MywiMTgiOjIwMjEsIjE5IjpmYWxzZSwiMjAiOmZhbHNlLCIyMiI6MSwiMjUiOiJzeW5kcm9tZSIsIjI2IjpbMSwyLDMsNCw1LDYsNyw4LDksMTAsMjJdLCIyNyI6WzQsMzEsNjQsMTAzLDEzNywxNTgsMTY2XSwiMjgiOlsyLDMsNCw1LDYsNyw4LDksMTAsMTEsMTIsMTNdLCIyOSI6WzEsMl0sIjMwIjpbMSw3LDExLDE3LDIzLDIyXSwiMzEiOlsiMS0xIiwiMS0yIl0sIjMyIjoiMS0xIiwiMzMiOlsxLDJdfQ== [Accessed 2025, January 28].

[5] World Health Organization. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva, Switzerland. World Health Organization. 2024. Available at: https://www.who.int/publications/i/item/9789240093461

[6] Wei, Y. Palacios Araya, D. Palmer, KL. Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics. Nature Reviews Microbiology. 2024. 22:705-721. https://doi.org/10.1038/s41579-024-01058-6

[7] Centers for Disease Control and Prevention. Staphylococcus aureus Basics. Available at: https://www.cdc.gov/staphylococcus-aureus/about/index.html [Accessed 2025, January 28].

[8] Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus (MRSA) Basics. Available at: https://www.cdc.gov/mrsa/about/index.html [Accessed 2025, January 28].

[9] NHS. Pneumonia. Available at: https://www.nhs.uk/conditions/pneumonia/ [Accessed 2025, January 28].

[10] Whiteway, C. Breine, A. Philippe, C. Van der Henst, C. Acinetobacter baumannii. Trends in Microbiology. 2022. 30(2):199-200. DOI: 10.1016/j.tim.2021.11.008

[11] Cystic Fibrosis Trust. Lungs and cystic fibrosis. Available at: https://www.cysticfibrosis.org.uk/what-is-cystic-fibrosis/how-does-cystic-fibrosis-affect-the-body/cystic-fibrosis-complications/lungs [Accessed 2025, January 28].

[12] Davin-Regli, A. Lavigne, J-C. Pagès, J-M. Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance. Clinical Microbiology Reviews. 2019. 32(4). DOI: 10.1128/CMR.00002-19 

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