ESKAPE Pathogens and Antimicrobial Resistance

The majority of nosocomial (hospital-acquired) infections are caused by a group of multi-drug resistant pathogenic bacteria known as ESKAPE Pathogens. A set of six extremely pathogenic bacteria known as ESKAPE is linked to serious nosocomial infections.

The acronym ESKAPE stands for
E= Enterococcus faecium
S= Staphylococcus aureus
K=Klebsiella pneumoniae
A= Acinetobacter baumannii
P= Pseudomonas aeruginosa
E= Enterobacter species 

Since the early 2000s, microorganisms that are resistant to antibiotics have been considered a severe threat to human health. The severity and frequency of infections have increased due to the emergence of drug-resistant bacteria, necessitating an urgent focus on the creation of new potent antibiotics. In February 2017, the World Health Organization (WHO) produced a list of diseases for which new effective treatments were urgently needed. This list was intended to standardize the surveillance and research on these growing drug-resistant bacteria. A set of pathogenic bacteria with the designation “ESKAPE” and a “priority status” are included in this lengthy list.

The Infectious Disease Society of America (IDSA) recognized these bacteria as significant nosocomial infection causes in 2004 before the WHO did. However, only drug resistance was given considerable consideration, and the WHO issued a warning about the dangers of antimicrobial resistance before ESPAKE became a matter of concern.

The majority of the bacteria in this group are included in the 2019 Antimicrobial Resistant Threat List published by the CDC (Center for Disease Control and Prevention). The serious threat list includes Pseudomonas, Staphylococcus, and Enterococci, while the urgent threat list includes Acinetobacter and Enterobacterales (Klebsiella, Enterobacter).

List of ESKAPE Pathogens
The following six pathogenic bacteria are represented among the multi-drug resistance strains in ESKAPE

Enterococcus faecium

  • It belongs to the genus Enterococcus, family Enterococcaceae, phylum Bacillota, and is a lactic acid fermenting, non-hemolytic, gram-positive cocci bacteria.
  • It is located in the human gastrointestinal tract (GI tract) and is a component of the human microbiome. They do, however, now regularly cause infections in hospitalized patients due to their multi-drug resistance. They have the capacity to form biofilm and are thus engaged in illnesses linked to medical devices.
  • Vancomycin-resistant E. faecium strains are the subject of particular attention (VR E. faecium).
  • For example, ventilator-associated pneumonia and other respiratory tract infections (RTIs), catheter-associated urinary tract infections (UTIs), catheter-associated surgical wound infections, and bloodstream infections have all been linked to vancomycin-resistant strains of E. faecium.

Staphylococcus aureus

  • S. aureus is a member of the genus Staphylococcus, family Staphylococcaceae, phylum Bacillota, and is a gram-positive, catalase-positive, facultatively anaerobic cocci bacteria.
  • It makes up most of the skin and nasal cavity’s natural flora. However, it is frequently described as an opportunistic pathogen that causes RTIs, bacteremia, sepsis, UTIs, and food poisoning, among other illnesses.
  • S. aureus is the most prevalent bacteria in everyone’s body and can form biofilms on medical equipment. They, therefore, represent the bulk of nosocomial infections globally. S. aureus is increasingly becoming a substantial hazard in hospital settings because of its resistance to the majority of existing therapies, leading to a rise in mortality in S. aureus infection cases.
  • Nearly 50% of staphylococcal infections are caused by Methicillin-Resistant Staphylococcus aureus (MRSA), the most prevalent drug-resistant strain of S. aureus. MRSA is classified as a superbug and is usually linked to sepsis, UTIs, and skin and soft tissue infections.

Klebsiella pneumoniae

  • A non-motile, oxidase-negative, gram-negative rod-shaped bacterium belonging to the Enterobacteriaceae family is K. pneumoniae.
  • It is present in small amounts as part of the skin’s and GI tract’s natural flora in humans. It is one of the most frequent infections causing bacterial pneumonia while being commensal. It can also cause UTIs, surgical site infections, and catheter-associated infections, although it primarily causes pneumonia in patients on ventilators and in intensive care units.
  • The pathogen on the list of immediate threats is K. pneumoniae which is carbapenem-resistant (CRKP).

Acinetobacter baumannii

  • A. baumannii belongs to the genus Acinetobacter in the family Moraxellaceae of the phylum Pseudomonadota and is a species of aerobic, glucose-non-fermentative, Cocco-bacilli, Gram-negative Gammaproteobacteria.
  • It typically exists in soil, water, and briefly in the flora of human skin. The number of nosocomial infections caused by A. baumannii is quickly rising, particularly RTIs, UTIs, and wound infections.
  • Carbapenem-Resistant A. baumannii (CRAB), which is on the CDC and WHO’s urgent threat list, is one of the most hazardous strains of A. baumannii. In hospitalized patients, CRAB is primarily linked to ventilator-associated pneumonia (VAP), urinary tract infections (UTIs), and wound infections.

Pseudomonas aeruginosa

  • P. aeruginosa belongs to the genus Pseudomonas, family Pseudomonadaceae, and phylum Pseudomonadota. It is a Gram-negative, rod-shaped, encapsulated, facultative anaerobic Gammaproteobacteria.
  • An opportunistic nosocomial bacteria called P. aeruginosa can seriously affect the blood, the urinary system, the respiratory system, and wounds. It is the most frequent pathogen responsible for burn wounds and external ear infections.
  • Globally, the number of P. aeruginosa strains that are multidrug-resistant is rising. Most of them have fought off treatment with conventional antibiotics. The mortality rate from an infection caused by such multiple-drug resistance bacteria can reach 60%. The CDC has added resistance to ciprofloxacin and levofloxacin to its list of significant threats.

Enterobacter species

  • A genus of Gram-negative, lactose-fermenting, facultatively anaerobic, rod-shaped Gammaproteobacteria belonging to the Enterobacteriaceae family in the Pseudomonadota phylum is called Enterobacter.
  • Numerous pathogenic species of Enterobacter, most of which infect immune-compromised people as opportunistic infections, are included. In the genus Enterobacter, common human infections include E. aerogenes, E. cloacae, and E. sakazakii.
  • UTIs and RTIs are frequently linked to Enterobacter spp. Multidrug-resistant species are especially challenging to treat since they are resistant to the majority of -lactams and cephalosporins.

Clinical Characteristics of ESKAPE Pathogens

ESKAPE, which is responsible for roughly two thirds of all nosocomial infections worldwide, has the greatest impact on hospital-acquired illnesses. According to the US CDC, there are already 2 million nosocomial infections with 23,000 ESKAPE fatalities in the US alone, and the situation is expected to get worse yearly.

The following illnesses in hospitalized patients are caused by ESKAPE pathogens

  1. Pneumonia Acquired in a Hospital
  2. Infections of the Urinary Tract
  3. Diseases of the Skin and Wounds
  4. Infection at the surgical site
  5. Bacteremia and Soft Tissue Infections from Endocarditis

ESKAPE Pathogens Epidemiology

The majority of ESKAPE pathogen reports come from hospital settings. There is an upward tendency in their occurrence rate. As of 2021, there are no accurate statistics available due to a lack of an effective surveillance system, but findings from US CDCs and other European studies show that their frequency is rising quickly. Among the ESKAPE pathogens, S. aureus is the one that causes the most infections.

Antimicrobial Resistance in ESKAPE Pathogens

Pathogens from ESKAPE are multidrug-resistant (resistant to more than three classes of antibiotics). The majority of the antibiotics that were previously used to treat these bacteria are ineffective against them.

Pathogens associated with ESKAPE have evolved resistance to all or the majority of antibiotics from classes including -lactams, -Lactamase -inhibitors, macrolides, ciprofloxacin, tetracyclines, lipopeptides, quinolones and fluoroquinolones, and oxazolidinones, as well as the last line of defense like the majority of polymyxins, glycopeptides.