The group of bacteria referred to as the ESKAPE pathogens are regarded the deadliest microorganism in the world. They consist of Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and finally Enterobacter species (Pendleton et al . 2013). These bacteria are implicated in the cause of most of the nosocomial infections worldwide. One characteristic that makes them deadly and difficult to handle is the fact that they are multidrug resistant. Multidrug resistance of microorganism is one of the greatest challenges that affect the clinical practice and the public health sector by extension. The primary causes of multidrug resistance include excessive usage of drugs, wrong use of antimicrobials, and also the use of substandard drugs in treatment. The development of microbial agents requires the proper understanding of these microbes and their resistance mechanism. These drugs have notably led to increased hospital-related illnesses that have increased morbidity and mortality rates, treatment costs, and the lack of trust in conventional medicine. The ESKAPE pathogen consists of both Gram-positive and Gram-negative pathogens which are life threatening especially to severely ill or immunocompromised patients. The discussion will analyze the characteristics that make the ESKAPE pathogens deadly microorganisms that have presented major challenges to the healthcare setting.
Resistance Mechanism to Antimicrobial Drugs
Some of the microbes are responsible for carrying resistance genes in their bacterial chromosome, transposons, or in the plasmid. Giedraitienė et al. (2011) asserted that the drug resistance mechanism falls under broad categories namely drug inactivation, modification of the target sites of the drug, alteration that occurs in the permeability of the cell resulting in reduced drug accumulation intracellularly, and finally the formation biofilm. To begin with drug inactivation or alteration, some of these bacteria release enzymes that modify and inactivate antibiotic drugs irreversibly. These enzymes include the beta-lactamases, chloramphenicol acetyltransferase, and aminoglycoside-modifying enzymes among many others. One of the common enzymes mostly produced by these bacteria is the beta-lactamases which hydrolyze the beta-lactam ring that forms part of the structure of all beta-lactams such as the penicillins and cephalosporins. Secondly, some of the bacteria escape recognition by the antimicrobial agents through modifying their target sites. An example of this mechanism is seen when the gene encoding for penicillin binding protein is mutated. Thirdly, some of the microbes have the ability to limit the amount of antibiotic drug content that can pass through cell membrane. Several mechanisms can be undertaken to ensure this happens such as the porin loss whereby the bacteria reduces the number of proteins on its cell membrane that allow for the passage of hydrophilic substances and antibiotics. Some bacteria also possess efflux pumps that act to increase the removal of antimicrobial contents from the intracellular parts of the cell. The pumps work to expel the drugs from the compartments at a rapid rate. Therefore, the drug concentration becomes insufficient to elicit an effect.
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Biofilm formation involves the formation of microbial communities that conglomerate to form a thin layer on either living or a non-living surface. All the microorganisms found in the biofilm can interact with one another and also with the environment. The biofilm is formed in a process that consists of three steps namely adhesion, growth and maturation, and thirdly detachment. Adhesion occurs when the bacteria reach the surface on which it intends to attach itself, growth and maturation involve when the bacteria releases materials that make the matrix and the maturation from colonies to layers, and finally detachment occurs when can either be active or passive. The process of active detachment is started by the bacteria while the external environment causes the passive detachment. The biofilms offer drug resistance through the mechanical, biological, and chemical support provided by the microenvironment which attenuates the activity of the antibiotics. The microenvironment constitutes low oxygen levels, low pH, high carbon dioxide levels and insufficient amounts of water. Under such conditions, it becomes difficult to kill the bacteria by the use of common antibiotics. Nutrient scarcity has also been identified as a factor that causes antibacterial resistance. Therefore, the bacteria that are found in the deeper layers of the biofilm are likely to exhibit more resistance to antimicrobials due to low nutrient levels. In the healthcare setting, pathogens most commonly found in biofilms include the Staphylococcus aureus, Klebsiella Pneumoniae, P. aeruginosa, and A. baumannii.
Antimicrobial Resistance and Pathophysiology in the ESKAPE Organisms
Enterococcus faecium
The fall under Gram-positive bacteria and are facultative anaerobes. They are normally found in pairs and chains. Their preferred target site is the gut region of human beings and animals. There are more than 20 species in the Enterococcus family, but the most virulent in the hospital setting are species of faecium and faecalis . The infections caused by these organisms are mostly acquired endogenously, but cases of cross-infection particularly between the hospital settings are common. Other factors that make the Enterococcus a dangerous species is their ability to survive under as high as 60 degrees Celsius temperature and also the fact that they can survive under salty conditions. The organisms have explicitly exhibited vancomycin-resistance, and therefore most vancomycin-resistant enterococci infections are as a result of these organisms. The virulence factors that have promoted resistance in these organisms include their genetic makeup which encodes for virulent factors, and their capacity to form biofilms.
The organisms also exhibit two types of resistance to microbial agents. They include intrinsic and the acquired resistance. This enables them to be serious causes of nosocomial infections. Intrinsically, the enterococci take advantage of the penicillin-binding proteins to tolerate beta-lactam antibiotics. They are also resistant to other antibiotics such as cephalosporins, penicillin, nalidixic acid, and macrolides among others. They also use folate acid that is already formed in them to bypass the prevention of folate synthesis hence making them highly resistant to trimethoprim-sulfamethoxazole.
Other than intrinsic resistance, enterococci also have the ability to depict acquired resistance. This type of resistance is shown to antibodies such as penicillin, tetracyclines, rifampin, and vancomycin among others. The intrinsic resistance involves genes that result in a peptide bond to which antibiotics such as vancomycin cannot bind. Therefore, the bacteria still have the ability to synthesize the cell wall.
Staphylococcus aureus
It is a Gram-positive bacterium that has a coccal shape. Its cells have a grape-like arrangement in clusters. It forms part of the normal flora, especially in the nasal and skin regions. Transmission can either be via direct contact or airborne route. The infections caused by this organism have over the past responded well to penicillin. However, the excessive use of the antibiotics has led to isolates that are resistant to penicillin G. The methicillin-resistance Staphylococcus aureus (MRSA), is one of the major cases of hospital related infections and the second largest cause of deaths especially in the United States. The bacteria exhibit a wide degree of resistance especially against the beta-lactams class of antibiotics such as penicillin, carbapenems, and methicillin among others. The drugs directed against the MRSA target its cell wall in the peptidoglycan membrane. However, the bacteria protect themselves by using molecules that soak the drug hence stopping it from penetrating into the cell wall. The microorganism has shown a slow evolution in resistance from traditional antibiotics to more recent antibiotics such as daptomycin and linezolid. Other resistant mechanisms that it has used to evolve include the use of enzymatic inactivation, altering the target site to reduce affinity with the antibacterial, trapping of the antibiotic and the use of the efflux pumps, and the acquisition of complex genetic materials that are resistant to the antimicrobial.
Most infections of MRSA occur in people who have been in the hospital setting for an extended period. This type of infection is referred to as Health-care associated MRSA. They are mainly caused due to invasive procedures that include surgeries, artificial joints, and intravenous tubing with a catheter. Another type of this infection is referred to as the community associated MRSA. It mainly spread via contact and manifests as painful boils on the skin. The risk factors for hospital-related MRSA include being hospitalized for long especially for young children, aged, and those whose immunity has been compromised. Those undergoing invasive medical procedures such as tubing, urinary catheters, and intravenous lines provide a pathway for these bacteria to get into the body. Thirdly, those who reside in long-term care facilities such as in nursing homes are at a higher risk of acquiring this dangerous type of Staphylococcus aureus. With regards to community-associated MRSA, the risk factors include participating in sports activities that involve contact where the bacteria can easily spread through cuts and abrasions created on the skin surface. Those who live in unsanitary conditions are also likely to be infected by MRSA. Finally, homosexuals are at a greater risk of getting MRSA due to the nature of their sexual activities. The MRSA infections resist most antibiotics and therefore very difficult to treat. Therefore, in most cases, infections spread throughout the body to an extent where they can be life-threatening. The infections associated with MRSA can infect the blood stream, organs such as the lungs and heart, bones and also joints.
Klebsiella pneumonia
It belongs to the broad members of the Enterobacteriaceae family. It is a Gram-negative bacillus that s non-fastidious and is encapsulated. The infections are also common in the healthcare setting and infections may be acquired through the endogenous or directly through contact. The microorganism has over the years acquired resistance through the beta-lactamase enzyme which can destroy the chemical structure of antibiotics having the beta-lactam structure such as penicillin and the cephalosporins. The organism has also developed a super enzyme that is known as the K.pneumoniae super enzyme that has helped to attain resistance against carbapenem. The organism is also known to be one of the major causes of multidrug-resistance globally. According to Nikaido, (2009), studies have also shown that there exists a strain that is resistant to colistin, which is regarded a last-line antibiotic. The resistance primarily arises from mutations that inactivate the regulatory gene referred to as mgr B.
Klebsiella organisms are resistant to most of the available antibiotic drugs. The length at which a patient stays at the hospital and the invasive procedure undertaken on them are significant risk factors for acquiring the bacteria. Treatment majorly depends on the organ that has been infected. Bacteremia may result in the modification of the treatment method. The mortality rate for community-acquired pneumonia is at 50%. Treatment includes identification of the gram-negative bacteria, ventilation, and finally proper supportive care. Clinical and radiological interventions can also be carried out to assess if there is a need for surgery to sort out infections resulting from pulmonary gangrene, empyema, and lung abscess. In the treatment of nosocomial based infections, it is important to select antibiotics that have a higher intrinsic activity. The K. Pneumoniae is also a common cause of urinary tract infections. This is enabled by invasive procedures in the urinary tract such as the insertion of urinary catheters.
Acinetobacter baumannii
The organisms are distributed in the environment widely and are prone to contaminate the hospital setting. One factor that increases the virulence of this organism is its ability to stick on human hands for a long time due to its extensive survivability. This can, in turn, lead to nosocomial infections due to high incidences of cross infection via contact. It is a Gram-negative non-fermentative organism and can cause infections at various sites on the body such as on the urinary and respiratory tracts. The organism has various resistant strains that lead to many problems in intensive care wards and surgical rooms. Due to its environmental resilience and resistance, it has been implicated in the major outbreaks both in the hospital environment and the community setting. Infections majorly occur to people who have an underlying infection, those immunocompromised, patients subjected to invasive procedures, and finally those treated with a broad spectrum of antibiotics. The mechanism for resistance is enabled by its genetic composition that enables it to genetic transform and to perform homologous recombination. They are also highly mutative and possess competent genes that take DNA from the environment. To beta-lactams, it possesses beta-lactamase an enzyme hydrolyzes the drugs. It also can convert to penicillin-binding proteins hence preventing the action of the drugs. It also reduces the number of porin proteins hence reducing the permeability of the antibiotic drugs and finally uses efflux pumps to pump out the contents of the drugs to avoid it accumulating to viable therapeutic amounts.
The bacteria have the ability to cause a wide range of diseases. Factors that increase the risk of acquiring infections by Acinetobacter include being immunocompromised, having chronic lung diseases, incidences of diabetes, long hospital exposure, use of hospital ventilators, treatment of the open wound in the hospital, and invasive procedures such as the use of urinary catheters. The bacteria can be transmitted by air, contact with objects, surfaces, and skin of infected people. The symptoms include pneumonia, infections in the blood stream commonly referred to as sepsis, meningitis, wound and infection in the surgical site, and unitary tract infections among many others (Bodro et al . 2013).
Pseudomonas aeruginosa
It is a Gram-negative bacterium that is rod shaped. It is a facultative anaerobe that forms part of the resident organisms at the gut. Carriage rates are relatively low in the community but higher in the hospital setting. Patients can either be infected through both endogenous and exogenous sources. The microbe is resistant to both disinfectants and antibiotics. The resistance arises due to the exposure of the bacterium to different medications. The bacteria acquire certain mutations enabled by the resistant genes hence allowing it to survive in the face of antibiotic treatment.
However, it is of the essence to note that the bacteria are an opportunistic pathogen that takes advantage of the already weakened host to initiate an infection as pointed out by Peterson, (2009). It can exist as a normal flora on the human skin provided that the body's immune system is not compromised. The infection with the microbe occurs in deep tissues such as in the blood or bone. The bacteria have extra characteristics that assist its virulence such as the availability of flagella to enhance movement; pili are vital in enhancing attachment to various sites, and also the lipopolysaccharide that forms the endotoxin. The bacteria have also exhibited the ability to grow under minimal media, less nutrition, and can survive in compromised environments. All these factors make P. aeruginosa very dangerous bacteria to deal with. It also forms a biofilm that attaches to the surface hence making it difficult to destroy. Infections by the bacteria affect the urinary tract, bloodstream, organs such as the ear and heart, bones and joints, respiratory tract, and skin among many others.
Enterobacter species
They are Gram-negative rods. Most infections are caused on immunocompromised hosts in hospitals. Just like the other classes of bacteria, the Enterobacter species have developed multi-drug resistance owing to the inappropriate use of antibacterials. They have developed genes that assist them in evading antimicrobial therapy such as using enzymes to escape beta-lactams such as penicillin and altering their target sites by use of protein porins as pointed out by Li and Nikaido (2009). It is endowed with virulent factors such adhesions, siderophores used for the acquisition of iron, and endotoxins to initiate infections. The manifestations include meningitis, lung infections, urinary tract problems, abdominal cavity diseases among others.
In conclusion, The ESKAPE pathogens are regarded as one of the deadliest microbes in the universe due to their multi-drug resistance and the fact that they are mostly hospital-based bacteria. They are highly resistant, pathogenic, and easily transmit diseases between people. The ESKAPE pathogens use various mechanisms to acquire resistance such as changing the drug target, enzymatic inactivation, biofilms that provide mechanical support, the use of efflux pumps and protein porin among others. The microbes are both clinical and public health concern and the prospect that they are still evolving is a dangerous trend and scientist need to do more to ensure that they invent drugs that cannot be evaded. However, research methods have been geared towards acquiring new antibodies that take advantage of their antivirulent strategies to come up with effective therapeutic mechanisms. Such research is a source of hope that the world will be free from these microbes that threaten the wellbeing of both human beings and animals.
References
Bodro, M., Sabé, N., Tubau, F., Lladó, L., Baliellas, C., Roca, J., & Carratalà, J. (2013). Risk factors and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in solid-organ transplant recipients. Transplantation , 96 (9), 843-849.
Giedraitienė, A., Vitkauskienė, A., Naginienė, R., & Pavilonis, A. (2011). Antibiotic resistance mechanisms of clinically important bacteria. Medicina , 47 (3), 137-146.
Li, X. Z., & Nikaido, H. (2009). Efflux-mediated drug resistance in bacteria. Drugs , 69 (12), 1555-1623.
Nikaido, H. (2009). Multidrug resistance in bacteria. Annual review of biochemistry , 78 , 119-146.
Pendleton, J. N., Gorman, S. P., & Gilmore, B. F. (2013). Clinical relevance of the ESKAPE pathogens. Expert review of anti-infective therapy , 11 (3), 297-308.
Peterson, L. R. (2009). Bad bugs, no drugs: no ESCAPE revisited. Clinical Infectious Diseases , 49 (6), 992-993
