ESKAPE Pathogens and the Global Crisis of Antimicrobial Resistance: Current Burden and Future Directions

This article was exclusively written for European Sting by Ms. Carolina Massarutto Cavarsan, a second-year medical student at the Faculty of Health Sciences of Barretos Dr. Paulo Prata (FACISB). She is affiliated with the International Federation of Medical Students Associations (IFMSA), cordial partner of The Sting. The opinions expressed in this piece belong strictly to the writer and do not necessarily reflect IFMSA’s view on the topic, nor The European Sting’s one.

Cavarsan CM¹. Jorge LS¹

1 Barretos School of Health Sciences Dr. Paulo Prata – FACISB, Barretos, SP, Brazil

Antimicrobial resistance (AMR) arises when microorganisms, including viruses, bacteria, fungi, and parasites survive exposure to antimicrobial agents and continue to cause infections in humans and animals. In 2019, AMR was associated with 4.95 million deaths worldwide (1) and The Global Burden of Disease (GBD) 2021 projects that AMR could be associated with 8.22 million global deaths in 2050 (2). 

 A substantial proportion of resistant infections in clinical practice is attributed to a critical group of pathogens, known as the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which pose a major global threat to human health (4). Despite the introduction of new antibiotics and adjuvants, such as novel β-lactamase inhibitors, the acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced treatment options for serious infections and elevated mortality rates due to treatment failure. 

Enterobacterales, a family of bacteria that often reside harmlesly in the gut, can acquire resistance and evolve to carbapenem-resistant Enterobacterales (CRE), causing severe infections which are rapidly spread and associaated with hight mortality (1). During the COVID-19 pandemic, a marked increase in multidrug-resistant organisms (MDROs) was observed, including CRE, wicth colonization rates rose from 6.7% in 2019 to 50% in March-April 2020 (3). 

 Several ESKAPE pathogens belong to the order Enterobacterales, including Klebsiella pneumoniae, Klebsiella aerogenes and Enterobacter cloacae. In 2020, carbapenem-resistant K. pneumoniae (CR-KP) rates exceded 50% in Belarus, Georgia, Greece, Moldova, Russia and Ukraine (4).

Staphylococcus aureus is a major human pathogen capable of causing skin and soft tissue infections, osteoarticular and bloodstream infections, pneumonia, infective endocarditis and device-related infections. Methicillin-resistant Staphylococcus aureus (MRSA) displays resistance to most β-lactams, including anti-staphylococcal penicillins (e.g., nafcillin, oxacillin and flucoxacillin) and cephalosporins (with the exception of ceftaroline and ceftobiprole) (4).

Enterococci, commensals of the human gastrointestinal microbiota, exhibit decreased susceptibility to penicillin and intrinsic resistance to cephalosporins. Risk factors for vancomycin-resistant enterococci (VRE) bloodstream infections include cancer or haematologic malignancy, solid organ transplantation, prolonged hospitalization, gastrointestinal tract surgeries and exposure to broad-spectrum antimicrobials. (4)

Pseudomonas aeruginosa is an opportunistic pathogen often associated with poor clinical outcomes. A prospective observational study in Italy reported that carbapenem-resistant P. aeruginosa (CRPA) infections were associated with higher 30-day mortality compared with carbapenem-susceptible infections. (4)

Carbapenem-resistant Acinetobacter baumannii (CRAB) represents another global threat, with a marked propensity to infect critically ill patients or those with multiple comorbidities. Carbapenem resistance vary substantially woldwide; in 2021, prevalence ranged from 0–5% in Western Europe and Scandinavia to over 80–90% in some countries of Southern and Eastern Europe, Latin America, Africa and the Middle East. (4)

Given the substantial clinical burden posed by antimicrobial-resistant ESKAPE pathogens, this chalenge requires a coordinated global response. This includes a thorough situational analysis or audit of current screening strategies to evaluate existing practices and identify critical caps. Strengthening surveillance and screening plays a key role in reducing patient mortality and limiting infectious complications, improving both individual outcomes and global pacient care. 

References

1. Almadhoon H, Ahmad I, Lee WWI, Matthews A, Carter ER, Otter JÁ et al. Prevalence of carbapenem-resistant Enterobacterales in healthcare and community settings in the UK: a systematic review and meta-analysis. J Hosp Infect 2025; 165:19-31. doi: 10.1016/j.jhin.2025.07.030. 
2. De Pascale G , Cortegiani A, Rinaldi M, Antonelli M, Cattaneo S, Cecconi M et al. Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study. Crit Care 2025;29(1):32.

doi: 10.1186/s13054-025-05266-1. 

3. Lai CC, Chen SY, Ko WC, Hsueh PR. Increased antimicrobial resistance during the COVID-19 pandemic. Int J Antimicrob Agents. 2021;57(4):106324. doi:10.1016/j.ijantimicag.2021.106324.
4. Miller WR, Arias CA. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nat Rev Microbiol 2024;22(10):598-616. doi: 10.1038/s41579-024-01054-w.

About the author

Carolina Massarutto Cavarsan is a second-year medical student at the Faculty of Health Sciences of Barretos Dr. Paulo Prata (FACISB). She serves as the Local Secretary of IFMSA Brazil and is a former member of SCOME, the Standing Committee on Medical Education. Carolina also works as the Director of the Medicina Solidária Project, contributes to the Student Union, and is an active member of the Academic League of Clinical and Surgical Cardiology.