For example, in the United States, hospital-acquired E. faecium infection rates were 14% of the total infections reported between 2011 and 2014, while A. baumannii presented 2% and up to 4% in Asia ^[7][22]. A database analysis in the United States conducted by Marturano and Lowery in 2019 ^[8][23] showed that ESKAPE pathogens represented 42.2% of total bloodstream infections. These results coincide with the Department of Plastic and Burn Surgery of the Affiliated Hospital of Southwest Medical University in Luzhou, China, informing us that 47.5% of bacterial isolates from burn patients corresponded to the ESKAPE group ^[9][24]. Furthermore, 55% of these isolates were identified as multidrug resistant (MDR). In Mexico, Sosa-Hernández et al. in 2019 ^[10][25] estimated that 42.2% of HAIs in a hospital during 2013–2017 were attributed to the ESKAPE group. In turn, in an intensive-care unit in Monterrey, Nuevo Leon, Mexico, in 2012, this group accounted for 64% of isolates and 86.2% of A. baumannii and 28.9% of P. aeruginosa were MDR ^[11][26]. ReThisearchers  review selected A. baumannii and P. aeruginosa to represent the ESKAPE group impact; these two species are among the greatest concerns due to their pathogenesis and high rates of resistance, morbidity, and circulation in hospital settings.

The epidemiology of bacterial resistance must include constant monitoring of the circulant pathotypes and antibiotic-resistant profiles. Therefore, in most countries, research must be expanded on monitoring and characterizing bacterial antibiotic resistance. This action is relevant because it would allow for a better understanding of this global challenge ^[12][27]. This situation represents a challenge since a correct antibiotic-resistance characterization is needed, but it is a long process. However, a proper approach to this phenomenon allows reusearchers  to understand its behavioral tendency in different environments. Therefore, since researchers this review intends to focus on these bacterial species as representative of MDR species, their epidemiological development is discussed more specifically.

The genus Acinetobacter is defined as “short pleomorphic coccobacilli that are Gram-negative, strict aerobic, catalase positive, oxidase negative, non-fermenting and immotile” ^[13][28]. Some species of this genus can be found in different environments; however, A. baumannii is mainly associated with hospital settings ^[13][14][28,29]. One million cases of infection are attributed to this species each year ^[15][30], with mortality rates ranging from 23 to 68% for HAI and up to 64% for community-acquired infections.

On the other hand, pathologies attributed to A. baumannii can be found in the respiratory tract, bloodstream, urinary tract, and wounds ^[16][10]. In Lebanon, Kanafani et al. ^[17][31] evidenced that respiratory tract infections caused by this pathogen accounted for 53.1% of total cases. It was found that 68.3% of A. baumannii isolates from ventilator-associated pneumonia (VAP) corresponded to Extensive Drug Resistance (XDR). In comparison, 13.3% was MDR and 18.3% Pan-drug resistant (PDR) ^[18][32]. Furthermore, an international meta-analysis revealed that A. baumannii MDR prevalence is related to hospital-acquired pneumonia and represents almost 80% of the analyzed cases ^[13][28]. The prevalence of antibiotic-resistant A. baumannii strains indicates the relevance of designing strategies for controlling their virulence and dispersion.

Pseudomonas aeruginosa is a Gram-negative, rod-shaped, non-fermenting, motile, oxidase-positive, facultative aerobic bacillus, considered a non-fastidious microorganism in terms of its growing conditions. It is ubiquitous and persistent in water and soil, although it is mostly associated with predominance in clinical settings ^[5][19][4,33]. According to statistics in the United States of America, 13–19% of nosocomial infections are attributed to P. aeruginosa, mainly affecting ICUs (Intensive-Care Units), and can represent up to 23% of all cases. Its presence is manifested in clinical conditions, such as pneumonia, skin, ear, eye, urinary tract, and bloodstream infections, the most frequent in the respiratory tract ^[5][19][20][4,33,34]. Up to 22% of all HAIs is described by healthcare-associated pneumonia and VAP, where P. aeruginosa accounts for 10–20% of isolates, with an estimated mortality of 32–42.8% ^[20][34]. These infection and mortality levels may be associated partly with the rapid development of resistance to therapeutic agents. According to the National Healthcare Safety Network, during 2015–2017, 26.3% of P. aeruginosa isolates in ICU patients with possible pneumonia had carbapenem resistance ^[20][34]. Therefore, it is urgent to monitor the development of this phenomenon.

The costs associated with bacterial-resistant infections could reach USD 100 trillion globally ^[1][21][1,2]. It could also reduce Gross Domestic Product by 2–5% in some countries, generating 24 million more people in extreme poverty by 2030 ^[1][22][1,35]. In addition, drug resistance can extend hospitalization periods, involving a greater risk of death, decreasing the quality of life, and requiring the use of drugs with a wider spectrum and higher cost ^[2][5][3,4].

The attack of antibiotic-resistant bacterial infections increases vulnerability in some daily clinical practices, such as surgery, organ transplantation, or chemotherapy ^[23][16]. Unfortunately, these consequences would be accentuated in the most vulnerable social strata, elderly, immunocompromised, and low-income populations ^[3][19]. Finally, it should be kept in mind that the consequences of this phenomenon cannot be solved only with the creation of new drugs but with worldwide political and social changes.

The development of antibiotic resistance has been conventionally attributed to two main mechanisms. The first mechanism involves the genetic responses triggered by the antibiotic challenge. The second mechanism considers a more complex system formed by environmental factors ^[24][36]. The genetic mechanisms of antibiotic resistance can be summarized in three general processes: regulation in antibiotic concentration, enzymatic antibiotic processing, and alteration of its target site ^[25][37]. More specifically, Serra-Valdés ^[2][3] lists the following mechanisms as the main ones: (i) Increased function of efflux pumps to release the antibiotic from bacterial cells. (ii) Hydrolytic enzymes to inactivate the antibiotic. (iii) Modifying PBP (penicillin-binding protein) to avoid antibiotic recognition. (iv) Decreased cell membrane permeability and biofilm development to block antibiotic access. (v) Overexpression of the target site. It is important to mention that all these responses can act simultaneously, taking a more complex picture.

In some ESKAPE group members, resistance mechanisms have a certain specificity. Resistance in A. baumannii is reflected in reduced membrane permeability, altered antibiotic target sites, and increased efflux pump function ^[26][38]. For example, overexpression of AdeABC efflux pumps, OmpA, CarO porins, and antibiotic hydrolysis provides resistance to A. baumanii against β-lactams. β-lactamases can be classified into four categories, A, B, C and D; A. baumannii has all four types of these enzymes, VIM, IMP, NDM, and ADC inherent to the species and OXA type. OXA-23 and OXA-51 are mainly involved in carbapenem resistance ^[25][37]. Resistance in P. aeruginosa has some variations when compared to A. baumannii; it used the expression of efflux pumps, Amp-C, BLEE, and metallo-β-lactamases, and modifications in PBP, OprD, and OprH porins ^[5][4]. Consequently, resistance systems and pathogenicity factors determine bacterial infections’ course and severity; these differences could be considered to direct antivirulence treatments at gene and protein levels.

The role played by environmental and consumer-behavior conditions in antibiotic resistance is of great relevance. The CDC ^[27][5] states the following list as the main events driving this phenomenon: (i) over-prescription of antibiotics; (ii) patients not following prescriptions; (iii) unnecessary use in agriculture; (iv) poor infection control in hospitals and clinical settings; (v) poor hygiene and sanitation practices in infected animals and plants; and (vi) lack of rapid laboratory tests for antibiotic-resistance detection. In addition, other factors, such as lack of access to clean water, poor access to quality drugs, vaccines, diagnostic tools, lack of awareness and knowledge, non-compliance with legislation, and indifference of pharmaceutical companies, also contribute to this problem. Hence, it is important to consider all these issues as priorities when taking action ^[5][24][4,36].