ESKAPE

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ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter spp. [1] The acronym is sometimes extended to ESKAPEE to include Escherichia coli . [2] This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). [1] As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. [3] P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. [4] P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. [5] [6] The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs (as pneumonia), blood, urinary tract, and in other body regions after surgery. [6] S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. [7] The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. [7] Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread. [8]

Contents

One of the main reasons for the rise in the selection for antibiotic resistance (ABR) and MDR which led to the emergence of the ESKAPE bacteria is from the rash overuse of antibiotics not only in healthcare, but also in the animal, and agricultural sector. [9] Other key factors include misuse and inadequate adherence to treatment guidelines. [10] Due to these factors, fewer and fewer antibiotic treatments are effective in eradicating ABR and MDR bacterial infections, while at the same time there are now no new antibiotics being created due to lack of funding. [10] These ESKAPE pathogens, along with other antibiotic-resistant bacteria, are an interweaved global health threat and are being addressed from a more holistic and One Health perspective. [6] [9]

Prevalence

From a global perspective, the emergence of multidrug-resistant (MDR) bacteria is responsible for about 15.5% of hospital acquired infection cases and there are currently about 0.7 million deaths from drug-resistant disease. [1] [11] Specifically, the opportunistic nosocomial ESKAPE pathogens correspond with the highest risk of mortality which has the majority of its isolates being MDR. [12] Two pathogens within the ESKAPE group, Carbapenem-resistant Acinetobacter and Carbapenem-resistant Enterobacteriaceae are currently in the top five of the antibiotic resistant bacteria on the CDC's 2019 urgent threat list, and the other 4 pathogens making up the group are on the serious threat list. [6] In addition, the World Health Organization (WHO) created a global priority pathogen list (PPL) of ABR bacteria with the goal to prioritize research and create new effective antibiotic treatments. [13] The global PPL classifies pathogens into 3 categories, critical, high, and medium, and has 4 of the pathogens from the ESKAPE group in the critical priority list and the other 2 pathogens that make up the group in the high priority list. [13]

Characteristics

ESKAPE pathogens are differentiated from other pathogens due to their increased resistance to commonly used antibiotics such as penicillin, vancomycin, carbapenems, and more. This increased resistance, combined with the clinical significance of these bacteria in the medical field, results in a necessity to understand their mechanisms of resistance and combat them with novel antibiotics. Common mechanisms for resistance include the production of enzymes that attack the structure of antibiotics (for example, β-lactamases inactivating β-lactam antibiotics), modification of the target site that the antibiotic targets so that it can no longer bind properly, efflux pumps, and biofilm production. [5] Efflux pumps are a feature of the membrane of Gram-negative bacteria that allows them to constantly pump out foreign material, including antibiotics, so that the inside of the cell never contains a high enough concentration of the drug to have an effect. [5] Biofilms are a mixture of diverse microbial communities and polymers that protect the bacteria from antibiotic treatment by acting as a physical barrier. [5]

Clinical threats

Due to their heightened resistance to frequently used antibiotics, these pathogens pose an additional threat to the safety of the general population, particularly those who frequently interact with hospital environments, as they most commonly contribute to hospital-acquired infections (HAI). The increased antimicrobial resistance profile of these pathogens varies, however they arise from similar causes. One common cause of antibiotic resistance is due to incorrect dosing. When a sub-therapeutic dose is prescribed, or a patient chooses to use less of their prescribed antibiotic, bacteria are given the opportunity to adapt to the treatment. At lower doses, or when a course of antibiotics is not completed, certain strains of the bacteria develop drug-resistant strains through the process of natural selection. [14] This is due to the random genetic mutations that are constantly occurring in many forms of living organisms, bacteria and humans included. Natural selection supports the persistence of strains of bacteria that have developed a certain mutation that allows them to survive. Some strains are also able to participate in inter-strain horizontal gene transfer, allowing them to pass resistance genes from one pathogen to another. [14] This can be particularly problematic in nosocomial infections, where bacteria are constantly exposed to antibiotics and those benefiting from resistance as a result of random genetic mutations can share this resistance with bacteria in the area that have not yet developed this resistance on their own.

Bacterial profiles

Enterococcus faecium

Enterococcus faecium is a Gram-positive sphereically shaped (coccus) bacteria that tends to occur in pairs or chains, most commonly involved in HAI in immunocompromised patients. It often exhibits a resistance to β-lactam antibiotics including penicillin and other last resort antibiotics. [14] There has also been a rise in vancomycin resistant enterococci (VRE) strains, including an increase in E. faecium resistance to vancomycin, particularly vancomycin-A. [14] These vancomycin-resistant strains display a profound ability to develop and share their resistance through horizontal gene transfer, as well as code for virulence factors that control phenotypes. These virulence phenotypes range from thicker biofilms to allowing them to grow in a variety of environments including medical devices such as urinary catheters and prosthetic heart valves within the body. [15] The thicker biofilms act as a “mechanical and biochemical shield” that protects the bacteria from the antibiotics and are the most effective protective mechanism that bacteria have against treatment. [5]

Staphylococcus aureus

Staphylococcus aureus is a Gram-positive round-shaped (coccus) bacteria that is commonly found as a part of the human skin microbiota and is typically not harmful in humans with non-compromised immune systems in these environments. However, S. aureus has the ability to cause infections when it enters parts of the body that it does not typically inhabit, such as wounds. Similar to E. faecium, S. aureus can also cause infections on implanted medical devices and form biofilms that make treatment with antibiotics more difficult. [14] Additionally, approximately 25% of S. aureus strains secrete the TSST-1 exotoxin responsible for causing toxic shock syndrome. [14] Methicillin-resistant S. aureus, or MRSA, includes strains distinct from other strains of S. aureus in the fact that they have developed resistance to β-lactam antibiotics. Some also express an exotoxin that has been known to cause “necrotic hemorrhagic pneumonia” in those with an infection. [14] Vancomycin and similar antibiotics are typically the first choices for treatment of MRSA infections, however from this vancomycin-resistant S. aureus, or VRSA (VISA for those with intermediate resistance) strains have emerged. [14]

Klebsiella pneumoniae

Klebsiella pneumoniae is a Gram-negative rod-shaped (bacillus) bacteria that is particularly adept to accepting resistance genes in horizontal gene transfer. It is commonly also resistant to phagocyte treatment due to its thick biofilm with strong adhesion to neighboring cells. [14] Certain strains have also developed β-lactamases that allow them to be resistant many of the commonly used antibiotics, including carbapenems, which has led to the creation of carbapenem-resistant K. pneumoniae (CRKP), for which there are very few antibiotics in development that can treat infection. [14]

Acinetobacter baumannii

Acinetobacter baumannii is most common in hospitals, which has allowed for the development of resistance to all known antimicrobials. The Gram-negative short-rod-shaped (coccobacillus) A. baumannii thrives in a number of unaccommodating environments due to its tolerance to a variety of temperatures, pHs, nutrient levels, as well as dry environments. [14] The Gram-negative aspects of the membrane surface of A. baumannii, including the efflux pump and outer membrane, affords it a wider range of antibiotic resistance. [14] Additionally, some problematic A. baumannii strains are able to acquire families of efflux pumps from other species, and are commonly first to develop new β-lactamases to improve β-lactam resistance. [14]

Pseudomonas aeruginosa

The Gram-negative, rod-shaped (bacillus) bacterium Pseudomonas aeurginosa is ubiquitous hydrocarbon degrader that is able to survive in extreme environments as well as in soil and many more common environments. Because of this versatility, it survives quite well in the lungs of patients with late-stage cystic fibrosis (CF). [14] It also benefits from the same previously mentioned Gram-negative resistance factors as A. baumannii. Mutants of P. aeruginosa with upregulated efflux pumps also exist that make finding an effective antibiotic or detergent incredibly difficult. [14] There are also some multi-drug resistant (MDR) strains of P. aeruginosa that express β-lactamases as well as upregulated efflux pumps which can make treatment particularly difficult. [14]

Enterobacter

Enterobacter encompasses a family of Gram-negative, rod-shaped (bacillus) species of bacteria. Some strains cause urinary tract (UTI) and blood infections and are resistant to multiple drug therapies, which therefore puts the human population in critical need for the development of novel and effective antibiotic treatments. [16] Colistin and tigecycline are two of the only antibiotics currently used for treatment, and there are seemingly no other viable antibiotics in development. [14] In some Enterobacter species, a 5–300-fold increase in minimum inhibitory concentration was observed when exposed to several gradually increasing concentrations of benzalkonium chloride (BAC). [17] Other Gram-negative bacteria (including Enterobacter, but also Acinetobacter, Pseudomonas, Klebsiella species, and more) also displayed a similar ability to adapt to the disinfectant BAC. [17]

One Health problem

The ESKAPE pathogens and ABR bacteria in general are an interconnected global health threat and a clear 'One Health' problem, meaning they can spread between and impact the environment, animal, and human sectors. [18] As one of the largest global health challenges, combatting the highly resistant and opportunistic ESKAPE pathogens necessitates a One Health approach. [12] One Health is a transdisciplinary approach that involves addressing health outcomes from a multifaceted and interdisciplinary perspective for humans, animals, and the environmental on a local, national, and global level. [9] Using this framework and mindset is crucial to combat and prevent the spread and development of the ESKAPE pathogens (including the ABR in general) while addressing its importantly related socioeconomic factors, such as inadequate sanitation. [9] New treatment alternatives for infections caused by ESKAPE are under current scientific research. [19]

Related Research Articles

<i>Staphylococcus aureus</i> Species of gram-positive bacterium

Staphylococcus aureus is a gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe, meaning that it can grow without oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA). The bacterium is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

<i>Acinetobacter</i> Genus of bacteria

Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.

<span class="mw-page-title-main">Hospital-acquired infection</span> Infection that is acquired in a hospital or other health care facility

A hospital-acquired infection, also known as a nosocomial infection, is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is sometimes instead called a healthcare-associated infection. Such an infection can be acquired in a hospital, nursing home, rehabilitation facility, outpatient clinic, diagnostic laboratory or other clinical settings. A number of dynamic processes can bring contamination into operating rooms and other areas within nosocomial settings. Infection is spread to the susceptible patient in the clinical setting by various means. Healthcare staff also spread infection, in addition to contaminated equipment, bed linens, or air droplets. The infection can originate from the outside environment, another infected patient, staff that may be infected, or in some cases, the source of the infection cannot be determined. In some cases the microorganism originates from the patient's own skin microbiota, becoming opportunistic after surgery or other procedures that compromise the protective skin barrier. Though the patient may have contracted the infection from their own skin, the infection is still considered nosocomial since it develops in the health care setting. Nosocomial infection tends to lack evidence that it was present when the patient entered the healthcare setting, thus meaning it was acquired post-admission.

<span class="mw-page-title-main">Colistin</span> Antibiotic

Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.

Vancomycin-resistant <i>Staphylococcus aureus</i> Antibiotica resistant bacteria

Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistant genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow bacteria to grow in the presence of the antibiotic. Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon. Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited. VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

<i>Pseudomonas aeruginosa</i> Species of bacterium

Pseudomonas aeruginosa is a common encapsulated, Gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. P. aeruginosa is able to selectively inhibit various antibiotics from penetrating its outer membrane - and has high resistance to several antibiotics. According to the World Health Organization P. aeruginosa poses one of the greatest threats to humans in terms of antibiotic resistance.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Imipenem</span> Carbapenem antibiotic

Imipenem is a synthetic β-lactam antibiotic belonging to the carbapenems chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus playing a key role in the treatment of infections not readily treated with other antibiotics. It is usually administered through intravenous injection.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

Enterococcus faecium is a Gram-positive, gamma-hemolytic or non-hemolytic bacterium in the genus Enterococcus. It can be commensal in the gastrointestinal tract of humans and animals, but it may also be pathogenic, causing diseases such as neonatal meningitis or endocarditis.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.

Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Examples of enzymes found in certain types of CRE are KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is a not-for-profit initiative created in 2015 reaching out to chemists in academia and research organisations who have compounds that were not designed as antibiotics and would not otherwise be screened for antimicrobial activity. These academic compounds are screened against a key panel of drug-resistant bacterial strains -superbugs. Multi-drug resistant microbes are a serious health treat, and exploration of novel chemical diversity is essential to find new antibiotics.

<span class="mw-page-title-main">Streptomyces sp. myrophorea</span> Species of bacterium

Streptomyces sp. myrophorea, isolate McG1 is a species of Streptomyces, that originates from a (ethnopharmacology) folk cure in the townland of Toneel North in Boho, County Fermanagh. This area was previously occupied by the Druids and before this neolithic people who engraved the nearby Reyfad stones. Streptomyces sp. myrophorea is inhibitory to many species of ESKAPE pathogens, can grow at high pH (10.5) and can tolerate relatively high levels of radioactivity.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

<span class="mw-page-title-main">Multidrug-resistant bacteria</span>

Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.

Kerry L. LaPlante is an American pharmacist, academic and researcher. She is the Dean at the University of Rhode Island College of Pharmacy. She is a Professor of Pharmacy and former department Chair of the Department of Pharmacy Practice at the University of Rhode Island, an adjunct professor of medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.

References

  1. 1 2 3 Mulani MS, Kamble EE, Kumkar SN, Tawre MS, Pardesi KR (2019). "Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review". Frontiers in Microbiology. 10: 539. doi: 10.3389/fmicb.2019.00539 . PMC   6452778 . PMID   30988669.
  2. ↑ Mahmood HY, Jamshidi S, Sutton JM, Rahman KM (2016). "Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps". Current Medicinal Chemistry. 23 (10): 1062–1081. doi: 10.2174/0929867323666160304150522 . PMC   5425656 . PMID   26947776.
  3. ↑ Rice LB (April 2008). "Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE". The Journal of Infectious Diseases. 197 (8): 1079–81. doi: 10.1086/533452 . PMID   18419525.
  4. ↑ Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (April 2010). "Antibiotic resistance of bacterial biofilms". International Journal of Antimicrobial Agents. 35 (4): 322–32. doi:10.1016/j.ijantimicag.2009.12.011. PMID   20149602.
  5. 1 2 3 4 5 Santajit S, Indrawattana N (2016-05-05). "Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens". BioMed Research International. 2016: 2475067. doi: 10.1155/2016/2475067 . PMC   4871955 . PMID   27274985.
  6. 1 2 3 4 CDC (2019). "Antibiotic Resistance Threats in the United States" (PDF). Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services.
  7. 1 2 Taylor TA, Unakal CG (2020). "Staphylococcus Aureus". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   28722898 . Retrieved 2020-11-13.
  8. ↑ Madigan MT, Bender KS, Buckley DH, Sattley WM, Stahl SA. 2015. Brock Biology of Microorganisms. 15th ed. London, UK: Pearson (Global Edition).
  9. 1 2 3 4 Collignon PJ, McEwen SA (January 2019). "One Health-Its Importance in Helping to Better Control Antimicrobial Resistance". Tropical Medicine and Infectious Disease. 4 (1): 22. doi: 10.3390/tropicalmed4010022 . PMC   6473376 . PMID   30700019.
  10. 1 2 Ma YX, Wang CY, Li YY, Li J, Wan QQ, Chen JH, et al. (January 2020). "Considerations and Caveats in Combating ESKAPE Pathogens against Nosocomial Infections". Advanced Science. 7 (1): 1901872. doi:10.1002/advs.201901872. PMC   6947519 . PMID   31921562.
  11. ↑ Dafale NA, Srivastava S, Purohit HJ (June 2020). "Zoonosis: An Emerging Link to Antibiotic Resistance Under "One Health Approach"". Indian Journal of Microbiology. 60 (2): 139–152. doi:10.1007/s12088-020-00860-z. PMC   7105526 . PMID   32255846.
  12. 1 2 Garvey M (July 2020). "Bacteriophages and the One Health Approach to Combat Multidrug Resistance: Is This the Way?". Antibiotics. 9 (7): 414. doi: 10.3390/antibiotics9070414 . PMC   7400126 . PMID   32708627.
  13. 1 2 "Global priority list of antibiotic-resistant bacteria to guide research, discover, and development of new antibiotics" (PDF). World Health Organization. 2017.
  14. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Pendleton JN, Gorman SP, Gilmore BF (March 2013). "Clinical relevance of the ESKAPE pathogens". Expert Review of Anti-Infective Therapy. 11 (3): 297–308. doi:10.1586/eri.13.12. PMID   23458769. S2CID   19213879.
  15. ↑ Stewart PS, Costerton JW (July 2001). "Antibiotic resistance of bacteria in biofilms". Lancet. 358 (9276): 135–8. doi:10.1016/s0140-6736(01)05321-1. PMID   11463434. S2CID   46125592.
  16. ↑ Ronald A (July 2002). "The etiology of urinary tract infection: traditional and emerging pathogens". The American Journal of Medicine. 113 (1): 14–19. doi:10.1016/s0002-9343(02)01055-0. ISSN   0002-9343. PMID   12113867. S2CID   13113431.
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  18. ↑ CDC (2020-03-13). "What Exactly is Antibiotic Resistance?". Centers for Disease Control and Prevention. Retrieved 2020-11-13.
  19. ↑ da Rosa TF, Coelho SS, Foletto VS, Bottega A, Serafin MB, Machado CS, Franco LN, de Paula BR, Hörner R (2020). "Alternatives for the treatment of infections caused by ESKAPE pathogens". Journal of Clinical Pharmacy and Therapeutics. 45 (4): 863–873. doi: 10.1111/jcpt.13149 . PMID   32339305. S2CID   216595082.
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