Extended-Spectrum Beta-Lactamase

Introduction

The modern medical practice continues to develop therapeutic and instrumental methods of treatment, which greatly facilitate and accelerate the process of patient recovery. There is no doubt that medical science has developed quite strongly over the past decades, and diseases that were considered untreatable before today can be inhibited, including by taking antibiotics. However, such widespread use of antibiological methods of treatment has led to the fact that some of the microorganisms have learned to produce immunity. First of all, it concerns pathogens producing expanded spectrum β-lactamases, ESBL. Thus, infections caused by microorganisms that produce such molecules can be treated with a limited number of antimicrobial agents. This work will focus on a discussion of epidemiological and pathophysiological specific disease associated with the production of ESBL enterobacteria.

Brief Description of the Problem

It is known that the nature of the caused disease can be classified as infectious if the cause of the deterioration of health is a pathogen parasitizing inside the human body. Standard clinical practice to combat such pathogens is to use antibiotic agents that actively inhibit the growth, development, and reproduction of bacteria in the body. A widely known class of such antimicrobial chemotherapy is β-lactam preparations: penicillins, carbapenems, or cephalosporins (Pandey & Cascella, 2019). Thus, due to the presence of the β-lactam ring, these drugs inhibit the synthesis of the bacteria cell wall, thus disrupting their activity in the patient’s body. However, it should be recognized that some of the mutated forms of Enterobacteria, such as E. coli, K. pneumonia, or P. aeruginosa (Seladi-Schulman, 2017). Apparently, under the influence of evolutionary engines of progress, these types of pathogens were able to develop antibiotic resistance by inhibiting the chemical activity of drugs.

Disease Description: History and Pathogenesis

Of primary importance is the recognition of the fact that ESBL infection is a natural continuation of pre-existing pathogens that acquired mutational defense mechanisms. Thus, studying the historical context of disease development, it is worth considering the complexity of identifying the starting point of infection. For example, E. coli, which often causes intestinal dysbacteriosis and bloody diarrhea, was first isolated by T. Escherich in 1885, and since then, numerous serotypes of the bacteria have been detected and investigated (Davis, 2018). However, it seems impossible to determine exactly when the pathogen has acquired mutational resistance to antibiotics. Nevertheless, it should be recognized that the first β-lactamase enzyme produced by a Gram negative pathogen was discovered back in 1960 in Greece (Munoz-Price, 2019). Subsequently, evidence of intense infection, particularly among children, was recorded throughout the 1990s in children’s wards of Greek clinics. Moreover, in 1988, the natural prokaryotic synthesis of this enzyme was first discovered in the United States areas (Seladi-Schulman, 2017). It follows that the antibiotic resistance of pathogens through ESBL has a long history, and by the beginning of the 21st century, it became a serious medical problem.

Infections caused by ESBL bacteria vary greatly depending on the nature of a particular microorganism. For example, the target organism of E.coli is the intestine, while K. pneumoniae may cause damage to the respiratory tract, brain tissue, or even the genitourinary system. In other words, the infection may be found in the blood, organ tissues, skin, or at the site of physical damage to the body. It follows that the specific symptomatic manifestations characteristic of ESBL infection depend on the area where the integrity of the body is affected. To facilitate the perception of this information, the specific symptoms and their ESBL pathogens are presented in Table 1.

Table 1: Symptomatic manifestations of ESBL-infection depending on the mutated pathogen 

# Pathogen Symptoms and signs
1 E.coli severe stomach cramps, bloody diarrhea, vomiting
2 K. pneumoniae fever, chills, cough, chest pain, flu
3 P. aeruginosa pus pimples, itching, chills, fever
4 P. mirabilis frequent urination, inguinal pain, hematuria

Therefore, the most common symptoms indicating the possibility of ESBL infections in the human body include blood in a stool, loss of appetite, difficulty breathing, dizziness, and pain. If the patient regularly experiences excessive abdominal bloating, cramps, and nausea combined with fever, this is a sufficient reason for mandatory medical supervision.

Epidemiological Data

It should be recognized that the diversity and ambiguity of symptomatic manifestations of pathogens with a pronounced resistance to β-lactam preparations generate relatively high infection statistics. In addition, a large number of deaths are provoked by the lack of adequate treatment, as it is known that classical antibiotics cannot cope with this problem. According to the CDC, by 2017, the total number of hospitalized patients with ESBL infection was 197,400, with about 9,100 deaths (CDC, 2019). Thus, the lethality rate of this disease surpassed 4.6% for 2017 which is quite a high indicator. Moreover, in a representative sample by Yousefipour et al.’s research (2019), the total infection rate among patients was 55.4%, with the predominant emphasis on urinary tract infections. In the same paper, the authors referred to earlier works by African colleagues that showed that 63% of adults and 100% of children were carriers of enterobacteria, causing ESBL infection. It was shown that of the participating patients, 26.5% of confirmed cases of E. coli and 43% of K. pneumoniae were ESBL positive. Similar prevalence data were found in a study by Nivesvivat et al. (2018), showing that 53.6% of patients had ESBL infection. The mortality rate in the group with infection was 38.9% vs. 13.3% for patients without such infection. These data suggest that ESBL infection statistics vary widely, although average infection rates and mortality rates are approximately similar.

Given this infection’s pathogenesis, infection in the medical setting is a high risk, as severe sterile clinic conditions stimulate mutational processes of resistance development. Thus, the risk group is primarily composed of patients who visit medical institutions more often than others: pensioners, pregnant women, and people with chronic diseases (CDC, 2019). At the same time, it should be understood that healthy people are also confirmed to be infected: as a rule, their urinary system is affected. Finally, a significant cohort of patients are people who actively use antibiotics to treat diseases and patients who have recently undergone surgery. Although there is no geographic dependence on this infection, the CDC has shown that some of the confirmed cases are among Americans who have returned from a trip abroad.

Prevention and Control

Decisions on prophylactic measures directly depend on the specifics of pathogen transmission: through mucous membranes, contaminated surfaces, contact with sick patients and animals. An intriguing way of infection is to stimulate bacteria to enter the body by developing a resistant infection caused by S. aureus (Biggers, 2017). Based on the above, the main prevention measures should be aimed at both clinical organizations and the patient (Thompson, 2020). Basically, this includes recommendations for frequent handwashing with soap, the use of alcohol-based disinfectants, careful washing of food, and observing food preparation modes. In addition, any scratches, wounds, or cuts must be treated with an antiseptic solution and covered with a sterile dressing. Items of personal hygiene, such as razors, towels, or toothbrushes, must be individual.

If ESBL infection is confirmed, the medical institution will decide to isolate the patient and ensure full control over the treatment of the patient. Staff, nurses, or relatives will be required to undergo hygienic hand and face treatments before entering the ward (Thompson, 2020). Sanitary and work surfaces inside the ward or room are also cleaned. The movement of a patient through the clinic must be limited and strictly regulated by wearing a safe uniform. Visiting the cafeteria, maternity ward, children’s areas, and recreation center is prohibited.

Hypotheses Testing

The materials proposed above clearly cover research questions about the nature and characteristics of ESBL infections. Although much has been studied, some hypothetical questions may still be asked. First of all, it concerns the rate of epidemic development. It seems that a few decades ago, only a small number of doctors spoke about the role of increased antibiotic resistance in increasing the mortality rate of patients, but over time, this issue is becoming more discussed. Thus, the first hypothesis is to determine whether the upward trend in ESBL cases is visible. Będzichowska et al. (2019) showed that during 2011-2015, the occurrence of a persistent pathogen increased fivefold, which may be further associated with hospitalization of asymptomatic patients. The same trends are confirmed by the quantitative study by Ponce-de-Leon et al. (2018), which observed epidemiological growth. In addition, it seems that in order to control this spread of the disease closely, a monitoring program of the clinic’s patients needs to be offered. Given that classical antibiotics prove useless for ESBL infections, it is necessary to prevent the possibility of mass infection. In this regard, it should be studied whether it makes sense to control the flow of patients in a clinical organization. The answer to this question can be found in Stadler et al. (2018), which showed that a systematic approach to patient monitoring makes it possible to monitor the spread of infection. Immediately from the above two hypotheses, it may be concluded that existing prevention measures are insufficient, as the number of diseases increases annually. For this reason, infection prevention policies should be intensified.

Conclusion

Summarizing the results of this work, it should be noted that the resistance of pathogens to antibiotics is a serious problem with the potential to create a public health crisis. It has been shown that some of the bacteria can create an enzyme that shows resistance to classic antibiotics: thus, these pathogens cannot be treated as standard. In fact, this is a serious challenge for medical science, as it means that it is necessary to find ways of therapy that could have been applied earlier but are no longer relevant. Then, a large group of microorganisms can produce this enzyme, which determines the spectrum of different pathophysiological conditions. It has been suggested and investigated that there has been an active growth in new cases of ESBL positive patients recently. At the same time, the initiation of a patient flow monitoring system could be a solution to maintain the rate of development.

References

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