Antibiotic Resistance and the Role of Nanoparticles as Antimicrobial/Adjuvant Agents

Photo by Adam Nieścioruk on Unsplash ABSTRACT Antibiotics are useful to stave off infection, though their misuse can be detrimental by creating drug-resistant infections. It is essential that we closely examine the leading causes of antibiotic resistance and consider the serious clinical and ethical ramifications around the issue. This paper will aim to achieve these goals, as well as to propose practical solutions directed towards combating this looming crisis. INTRODUCTION As drug companies race to develop vaccines and treatments in response to the COVID-19 pandemic, other impending public health threats may easily be forgotten and tucked away for another day. Experts are warning that “the same governmental inaction that helped foster the rapid, worldwide spread of the coronavirus may spur an even deadlier epidemic of drug-resistant infection…”[1] Dr. Jeffrey R. Strich, a researcher at the National Institutes of Health Clinical Center remarked, “If there’s anything that this COVID-19 pandemic has taught the world, it is that being prepared is more cost-effective in the long run.”[2] Antibiotic resistant infections cause an estimated 700,000 annual deaths globally.[3] According to the Centers for Disease Control, in the United States alone, drug resistant infections sicken 2.8 million people annually and are responsible for at least 35,000 deaths each year.[4] The United Nations has suggested that, if the problem is not soon addressed, antibiotic resistant infections could kill up to 10 million people by 2050.[5] The genesis of antibiotic resistance is complex and multifaceted. Successfully combating antibiotic resistance will require a global response. This paper will closely examine the leading causes of antibiotic resistance. It will also devote discussion to the clinical and ethical ramifications of antibiotic use and misuse. Lastly, the paper will propose practical measures that countries, such as the US, should be taking now to help stem this ever-evolving public health emergency. I. Antibiotic misuse Antibiotic resistance develops when bacteria are exposed to antibiotics, and propelled by the forces of evolutionary selection, mutate over time to adapt to the antibiotics.[6] This process is greatly accelerated when bacteria are overexposed to antibiotics.[7] Overexposure occurs in two primary ways – the first is through overuse/misuse of antibiotics in humans and the second is misuse/overuse in animals. A. In humans According to studies, treatment decisions involving antibiotics, including whether to use an antibiotic, which antibiotic to use, and the appropriate duration of such use, are incorrect in 30 percent to 50 percent of cases.[8] Antibiotics may be overprescribed in cases where they are not truly needed, or the wrong type or dosage of antibiotic can be prescribed. These issues can contribute to the problem of antibiotic resistance.[9] In many cases, faulty clinical determinations can be attributed to the lack of available microbial testing. Consequently, healthcare providers are unable to properly identify and classify bacteria, thus impairing their ability to make clinically sound treatment decisions. In one US study involving hospitalized patients suffering from community acquired pneumonia, for example, a pathogen was identified in only 7.6% of cases.[10] There is existing technology, specifically polymerase chain reaction (PCR) and semiquantitative PCR, that accurately identifies pathogens in approximately 89 percent of cases.[11] However, this technology is not widely used. When healthcare providers do use testing, they often rely upon culture testing, which is not rapid response and can delay proper treatment assessments.[12] As a result, providers may substitute inappropriate antibiotics in the interim. Another type of antibiotic misuse among humans occurs when patients stop their antibiotic regimens prematurely, thereby allowing harmless bacteria, not fully eradicated due to the abbreviated treatment, to acquire resistance. This resistance is then genetically transferred to dangerous bacteria.[13] Antibiotic resistance is also an unfortunate, frequent occurrence in developing countries where antibiotics are often available without a prescription and can be accessed through unregulated supply chains.[14] Developing nations also frequently suffer from a dearth of standard antibiotic treatment guidelines, which further precipitates antibiotic overprescribing.[15] B. In animals Approximately half of the world’s consumption of antibiotics is for agricultural purposes.[16] In the US, only 20 percent of antibiotic sales are intended for human use, while the remaining 80 percent is for use in livestock.[17] Despite this gross disparity, only 10 percent of publications discussing antibiotic resistance address the role that misuse of antibiotics in animals plays.[18] Antibiotic misuse in animals contributes to antibiotic resistance. Farmers and agribusinesses widely distribute antibiotics, through feed or water, to healthy animal populations for non-therapeutic purposes -- including for growth promotion and disease prevention.[19] The need for antibiotic use for disease prevention arises when animals’ living quarters are cramped and prone to disease.[20] Low concentrations of antibiotics have routinely been observed in the gastrointestinal tracts of livestock.[21] The presence of sub-therapeutic levels of these drugs fosters the growth of resistant bacteria and antibiotic resistance genes in the animals’ guts.[22] When the animals that have developed these resistant bacteria and genes are used as sources of food, both the bacteria and genes are passed along to the food supply, contaminating milk, meat, and eggs.[23] Because the antibiotics used in animals are those that have critically important human applications, the resistant bacteria and genes that develop in response to these drugs can destroy the prospect of their use as effective treatment options in both animals and humans.[24] According to the Environmental Working Group, supermarket meat and poultry contain extremely high levels of antibiotic resistant bacteria. Specifically, ground turkey was found to contain 79 percent resistant bacteria, pork 71 percent, ground beef 62 percent, and chicken 36 percent.[25] While antibiotic resistant bacteria may be killed with proper levels of heat (from cooking, for instance), antibiotic resistance DNA that accompanies the bacteria is not always eradicated. This resistance can then be transferred to the humans who consume it, conferring resistance upon otherwise benign bacteria in their digestive systems.[26] Resistant bacteria and genes contained in animal waste can also enter the environment as pollutants, settling in the ground, air, and water systems.[27] This further increases the transmissibility of antibiotic resistance from animals to humans and, ultimately, from human to human when a person acquires an antibiotic resistant infection from food and/or the environment and passes it along to others.[28] Another unintended adverse consequence of antibiotic use in animals is that foods like meat, milk, and eggs often contain antibiotic residues.[29] Since up to 90 percent of antibiotics are excreted through an animal’s waste, the drugs may also pollute the ground and groundwater.[30] Unnecessarily prolonged exposure to antibiotics increases the risk of acquiring bacterial resistance and/or an antibiotic resistant infection. The constant exposure to antibiotics can have other adverse health effects, ranging from drug hypersensitivity to carcinogenic effects.[31] II. Ethical considerations and obligations of stakeholders A. Tackling antibiotic resistance created through the healthcare sector First, with respect to antibiotic misuse in humans, there needs to be vastly scaled-up pathogenic testing. This will help ensure that treatment decisions involving antibiotics are made with empirical data, rather than being an exercise in supposition. Increased testing would lead to a reduction in unnecessary antibiotic prescriptions and scripts for the wrong antibiotic. PCR technology should be made widely available, at least until more effective testing is developed. At the most basic level, physicians should seek out this testing to make it available in their practices and hospitals. Third-party payors should be poised to approve the costs associated with these tests, since they may expedite improvements in patients’ health, thereby resulting in an overall cost savings. The pharmaceutical industry should also develop accurate, rapid testing technology. Rapid testing could abbreviate patients’ immediate illnesses, because knowledge provided by testing can help physicians quickly determine proper diagnoses. This will allow them to immediately prescribe the correct antibiotics. Finally, on a global level, countries that lack regulations around antibiotic access and use must implement sufficient restrictions. Addressing antibiotic resistance on a global level is imperative. Like with COVID-19, from a pragmatic and ethical perspective, we must create global solutions to antibiotic resistance to prevent resistant bacteria from spreading.[32] B. Ethical considerations around antibiotic prescriptions for human use Some ethicists have argued that antibiotics are a public good, and their overuse can result in a sort of “tragedy of the commons.”[33] In order to ensure the equitable distribution of antibiotics for all patients, society must create disincentives around antibiotic use. One such proposal involves taxing patients who use antibiotics for “minor and self-limiting” infections.[34] However, patients should not be punished for following their physicians’ recommendations. Things like taxing schemes unjustifiably interfere with the doctor-patient relationship and can result in adverse clinical consequences for patients. Others have asserted that physicians owe a duty of care to both present and future patients. Pursuant to this argument, physicians are ethically justified in increasing the risk of harm to present patients by a “small” amount by denying them antibiotics, if, in doing so, they are decreasing a significant risk of harm to future patients.[35] As per the Hippocratic Oath, physicians have an obligation first and foremost, to their current patients. This duty includes the obligation to act for the good of the patient (with beneficence) and to prevent harm from befalling the patient (non-maleficence). Nowhere in the Oath does it say that “a little” harm is acceptable. Failing to provide a patient with an antibiotic when it is warranted in order to “preserve” the drug for use by future patients is a violation of the physicians’ bioethical obligations to the patient. There are cases where it may be in patients’ best interests to avoid antibiotics, thus decreasing their own risk of antibiotic resistance from superfluous use. However, physicians must make these determinations on a case-by-case basis, relying on clinical evidence, rather than an impermissible ethical imperative to future patients. It is also a breach of the patient’s right of autonomy if the patient believes the physician is acting strictly in his or her best interest and relies on the physician’s treatment recommendations due to this belief. From a clinical perspective, a “small” amount of harm could easily become a “large” amount of harm, depending upon the patient and the infection at issue. A physician could also misjudge the level of risk involved in depriving a patient of an antibiotic, thereby creating an increased risk of morbidity or mortality for the patient. This is not to imply that the physician is never justified in proposing a reasonable waiting period before prescribing an antibiotic in order to determine if the illness is self-limiting and begins to improve on its own. However, again, this decision should be driven strictly by clinical criteria and the best interest of the present patient. In addition, proposals that seek to disincentivize antibiotic use can be clinically and ethically dangerous. Although prudence around antibiotic use is necessary, physicians should not be dissuaded from prescribing them when, in the physicians’ clinical judgements, they are necessary. Without antibiotics, seemingly benign infections can quickly turn deadly. Untreated bronchitis can rapidly progress to pneumonia. Untreated strep throat can lead to heart damage. A lingering urinary tract infection can induce sepsis.[1] III. Combating antibiotic resistance created by the agricultural sector As one scholar aptly observed, “[t]he current debate on the ethics of [antimicrobial resistance] is heavily and disproportionately focused on the use of antibiotics in humans…this focus reflects the traditional discourse in medical ethics…”[36] It seems relevant to note the seeming irrationality of ethicists advocating for withholding antibiotics from people while failing to consider the widespread, indiscriminate, unregulated use of antibiotics in the agricultural sector. The bottom line is that the focus on antibiotic use in humans, while important, cannot overshadow the substantial role that antibiotic use in animals has played in the antibiotic resistance crisis. There are several key stakeholders that are under an ethical obligation to take immediate action. The FDA should create a rule immediately banning the non-therapeutic use of antibiotics in healthy animals. The FDA took a small step in 2017 towards limiting antibiotic use in healthy animals when it finally restricted farms from using medically important drugs as growth promotion agents for animals.[37] This move, however, has been described as grossly insufficient. For one, antibiotics can still be used in healthy animals for purposes other than growth promotion, such as for “preventive health” purposes or in “times of stress,” which the FDA never clearly defines.[38] Therefore, the newly imposed restriction is easy to circumvent. Farms simply can purchase antibiotics for use as a “preventive health” measure rather than for growth promotion purposes.[39] To complicate matters further, at least 30 percent of antibiotics intended for animals have labels that lack any parameters around duration of use, meaning they can be used indefinitely throughout animals’ lives.[40] Farms and pharmaceutical companies are still promoting “growth” as an ancillary benefit of antibiotics, encouraging their unbridled use.[41] The next measure that the FDA must implement is the elimination of crowded, inhumane animal conditions in farms which create the need to administer “preventive” antibiotics. It is well established that “[a]ntibiotics are used at subtherapeutic levels to promote growth and to prevent disease in the extremely crowded conditions that food animals are raised in.”[42] The conditions present in many livestock farms has been compared to crowded hospitals “where everyone is given antibiotics, patients lie in unchanged beds, hygiene is nonexistent, infections and re-infections are rife, waste is thrown out the window, and visitors enter and leave at will.”[43] Eliminating crowded conditions will greatly reduce the need for preventive antibiotics. Finally, the FDA must establish a surveillance and enforcement mechanism to ensure proper compliance with limiting antibiotic use in healthy animals and addressing crowded conditions. Surprisingly, and notwithstanding the documented link between antibiotic use in animals and adverse human health effects, the FDA lacks any means of monitoring farms’ use of antibiotics in animals. The only measure it uses to assess possible antibiotic use is the sale of antibiotics to farms.[44] The pharmaceutical and chemical companies that manufacture the antibiotics are required to provide this information to the FDA.[45] Although reports have indicated that around 80 percent of antibiotics are sold for agricultural purposes, the FDA contends that it cannot discern actual use from these numbers. At the same time, the FDA has failed to create any other rules that would establish an alternative means of monitoring use.[46] As a New York Times investigation revealed, public health investigators are often unable to access the most basic information regarding a farm’s practices.[47] The agricultural industry constructs roadblocks so that the government’s access to farms, and how they are using antibiotics in animals, is hindered.[48] Further complicating the matter are conflicts of interest where livestock industry executives hold high positions on advisory committees for government agencies, such as the US Department of Agriculture (USDA).[49] The USDA does have a monitoring system that studies antibiotic use in the agricultural sector.[50] However, as an expert in a recent Washington Post article opined, “[t]he USDA’s oversight is laissez-faire. They test such a small fraction it can’t even be taken seriously…and they rotate the drugs they are testing for, because they can’t afford to test for all of them. They just don’t have the funds to do it. We raise 9 billion animals, and they test hundreds of cattle, not even thousands.”[51] The USDA’s antibiotic surveillance system also relies upon agricultural industry self-reporting, using voluntary questionnaires,[52] which calls into question the completeness and veracity of the data. In addition to the US government, the pharmaceutical industry must also help reign in imprudent antibiotic use in the agricultural sector. In 2007, legislation was introduced that would have required drug manufacturers to phase out use of antibiotics for healthy animals.[53] The meat and poultry industries, and several major pharmaceutical companies opposed the legislation.[54] It is ethically incumbent upon the pharmaceutical industry to support the fight against antibiotic resistance. The industry creates the products, doing a great deal of good, so some may argue they should not be tasked with overseeing poor uses of their products. But the pharmaceutical industry should encourage measures that ensure the responsible use of their products. It should also refrain from touting the “ancillary benefits” of antibiotics, such as “growth promotion,” which encourages their injudicious and illegal use. Consumers pay the ethical price of all three industries’ actions. People eating animal products have no opportunity to consent to the use of antibiotics. Although they may choose antibiotic-free meat and dairy, or choose not to consume animal products, people do not have the opportunity to consent to the presence of antibiotic residues, antibiotic resistant bacteria, and resistance genes in their food supply, and they may not be aware of the risks. Consumers bear the burden while industries profit. While there are animal food products designated “organic,” and their producers allege that no antibiotics were used in their production use, these foods tend to be significantly more expensive than food that is not organic. Therefore, those in lower socio-economic brackets are forced to buy foods that are detrimental to their health, while those in higher brackets can afford healthier food products. This is a violation of the ethical principle of distributive justice. Industry must work to find innovative ways to level the playing field and make all food safe for consumers, regardless of economic disposition. Simply put, no consumer should have to worry about antibiotics, antibiotic resistant bacteria, or resistance genes in their food supply. IV. Creating incentives around antibiotic development Addressing antibiotic resistance by chipping away at its causes is an important approach, though it is not sufficient to truly win the antibiotic resistance war. Since, even with mitigation of causal factors, resistance is inevitable on some level. Therefore, we must also address the crisis from the tail-end. This involves ensuring that, when resistance does occur, we are prepared for it. In order to do this, new classes of antibiotics that have the potential to treat resistant pathogens must be developed. The current landscape for antibiotic research and development is a barren one. Pharmaceutical companies have largely bailed on this area and biotechnology startups are going bankrupt pursuing this venture. As a recent New York Times piece noted, “[i]n the 1980s, there were 18 major pharmaceutical companies developing new antibiotics; today there are three.”[55] Pharmaceutical companies prefer to focus on the development of drugs for chronic diseases, which ensure long term, continuous profits.[56] Antibiotics, on the other hand, tend to be prescribed on a short-term basis for acute infections. This limits their inherent capacity to generate profits.[57] Finally, physicians tend to be reluctant to use new antibiotics, further limiting companies from recouping their investments.[58] Bioethicist Dr. Ezekiel Emanuel has suggested using for new classes of antibiotics, that “[t]he and of created by such a would make an in research pharmaceutical companies are their and using it to biotechnology companies to developing antibiotics in with the Health The companies that they are creating a billion for The the will be short-term intended to provide an a antibiotics The will to approximately companies on Although the are they are not new antibiotic can cost billion to The of to the research and development of new antibiotics may be a more As an article in the New of in to generate continuous growth to up – high of over There is also to drug Some such as the and the for have to contribute to antibiotic the for will be to raise pharmaceutical such as the with government could be directed antibiotic development Antibiotic resistance is a for everyone around the and the problem focused As the Health has observed, the antibiotic resistance crisis may and compared to the COVID-19 resistance needs more and As one public health expert has all of need an antibiotic. 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BackgroundAlthough inappropriate antibiotic use could contribute to the spread of antimicrobial resistance, data on the knowledge, attitude and practice of antibiotic use and resistance among patients in north-western Ethiopia are scarce. This study assessed patients’ knowledge, attitudes and practices regarding antibiotic use and resistance in selected public hospitals of Amhara regional state, Ethiopia.MethodsA cross-sectional study was conducted in selected public hospitals of Amhara regional state from November to December 2020 to assess the knowledge, attitude, and practice of patients on antibiotic resistance and use. Data were collected from 233 participants using a structured questionnaire and analyzed using SPSS version 23.ResultsAccording to the findings, 60.3% of the participants obtained their antibiotics without a prescription from private pharmacies, and the most commonly used antibiotic to treat human diseases was ampicillin (70.7%). Even though 69.8% of the patients heard about antibiotics and antibiotic resistance from several sources, 68.1–87.9% of them were unaware on the factors that contribute to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animal health. Using the mean score of 3.15 ± 0.08 as the cut-off, 37.5% of patients know about antimicrobial resistance and use. With a mean score of 27.6 ± 0.3, 45.3% of patients had positive attitudes toward prudent antibiotic use and resistance. About 44% of participants had a good practice, with a mean practice score of 4.95 ± 0.17. A higher level of education was associated with better knowledge, positive attitudes, and better practices regarding antibiotic use and resistance. Although 57.3% of respondents viewed poor handwashing practices in hospitals as a major factor contributing to increased antibiotic resistance, 59.9% of respondents viewed implementing hygiene, infection prevention, and control practices as a major strategy contributing to reducing antibiotic use and resistance.ConclusionAccording to the present study, there is a low level of awareness among patients about the proper antibiotics use and resistance. It is essential to raise awareness, develop, and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area.

Inappropriate use of antibiotics in animal and human plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. Although extensive use of these antibiotics could contribute to the development of drug resistance, information on the knowledge, attitude and practice of antimicrobial resistance and use among animal farm owners/workers in north western Ethiopia is rare. The objective of the present study was to assess knowledge, attitude and practice of animal farm owner/workers towards antibiotic resistance and use in Amhara regional state north western Ethiopia. A cross sectional study was conducted in selected cities of Amhara regional state from January to February, 2020. Data was collected from 91 participants using structured questionnaire and analyzed using SPSSS version 23. The results showed that 96.7% of respondents gave antibiotics to treat their livestock from different sources. Most of the respondents bought their antibiotics from private pharmacies without prescription and the most frequently mentioned antibiotics used to treat animal diseases was tetracycline (76.9%), followed by ampicillin (72.5%). Although, 90.1% of the animal farm owners heard about antibiotics and antibiotic resistance from different sources, they did not know the factors contributing to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animals’ health. Using the mean score 4.44 ± 0.15 as the cut-off, half of the animal farm owners/workers had good knowledge about antimicrobial resistance and use. 52.5% of animal farm owners/workers had positive attitudes towards wise antibiotic use and resistance with a mean score of 28.4 ± 0.5. However, 52.75% participants had poor practice with the mean score of practice 4.95 ± 0.17. Better knowledge, positive attitudes and better practices on antibiotic use and resistance were associated with farm owners/workers who engaged in higher education. Although poor awareness on antimicrobial resistance was perceived by 76.9% of respondents as very important factors that contribute to increasing antibiotic resistance, increasing the use of complementary treatments was perceived by the majority of respondents as very important strategies that contribute to reduce antibiotic use and resistance. The current study disclosed that there is low level of awareness among animal farm owners about the correct use of antibiotics and resistance. It is necessary to raise awareness, develop and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area.

The relationship between antimicrobial drug use and resistance rates and the implications for antimicrobial formularies are described. Efforts to restrict antimicrobial drug use to reduce resistance in certain microorganisms have been accompanied by increases in resistance in other microorganisms. Random cycling of a variety of antimicrobial agents to treat infections caused by the same microorganism in different patients within a health care institution has been advocated as a means to reduce antimicrobial resistance. Analysis of actual antimicrobial drug use and resistance data from a network of 40 hospitals revealed wide variability in antimicrobial use. The specific type and volume of antimicrobial agents used appear to play key roles in determining resistance rates. It may be feasible to optimize diversity in antimicrobial drug use and minimize resistance by making judicious changes to the antimicrobial formulary.

Resistome in a changing environment: Hotspots and vectors of spreading with a focus on the Russian-Ukrainian War

In the production of livestock products with therapeutic and prophylactic purpose, use antimicrobial drugs. Over time, pathogenic microorganisms develop mechanisms for adaptation to the negative effects of antibiotics. This phenomenon is called the acquisition of antibiotic resistance by a microorganism. At the global level, the question arises about the addiction of pathogenic microorganisms to certain types of antibiotics. The mechanism of addiction of pathogenic microorganisms to the use of antibiotics gave a significant impetus to pharmacologists to obtain our antimicrobial drugs. Aim: to investigate the current world experience in the study of the spread of antibiotic resistance pathogenic microorganisms and the main integration and the communication principles of combating this phenomenon. Results. The paper discusses the analysis of monitoring results under the auspices of the OIE for the dissemination of antibiotic-resistivity of microorganisms in 2013-1016. A parallel between the emergence of new antibiotics on the world veterinary market and the acquisition of the resistance of pathogenic microorganisms to new antimicrobial dosage forms have been made. The main causes of distribution and principles of struggle against antibiotic resistance of pathogenic microorganisms are highlighted. Attention is drawn to the fact that the increase of the industrial production of livestock products in Ukraine, the increase in the intensity of international trade in agricultural products, the large number of internally displaced persons, the migration of people, birds, and terrestrial wildlife contribute to the intensification of the issue of combating the spread of antibiotic resistant pathogenic microorganisms. It is suggested that the global problem of antibiotic resistance of pathogenic microorganisms at the present stage is controlled only in two ways, namely, legislative regulation of the circulation and use of antibiotics and the collection of information on the use of antimicrobial drugs in various fields of human activity. Regarding the monitoring of the presence and migration of antibiotic resistant strains of microorganisms, this issue is dealt with in varying degrees only in developed countries. This necessitates the adoption of a national program for controlling the circulation of antibiotics and the spread of antibiotic-resistant pathogenic microorganisms. The development of a national program to combat the spread of antibiotic resistant strains of microorganisms in Ukraine should be based on the principles of WHO and OIE, but the deduction of the peculiarities of our domestic legislation, livestock production, pharmacological and laboratory facilities is of key importance.

Antimicrobial resistance is a major threat to global health, and inappropriate drug use, including antibiotic self-medication, has been identified as an important factor in developing countries. This study assessed the knowledge, and attitude of antibiotic use and antibiotics resistance, as well as the practice of self-medication among healthcare workers. This is a cross-sectional study conducted in a federal teaching hospital in Southwest, Nigeria among 320 healthcare workers selected through a two-stage sampling technique. A thirty-four-item self-administered semi-structured questionnaire adapted from the questionnaire on antibiotic resistance: multi-country public awareness survey by the WHO was used for data collection. Descriptive statistics, cross-tabulation and logistic regression were carried out using SPSS version 25.0. The mean ±SD age of the participants was 36.3 ±9.2years and over one-third (37.5%) of them had 6-10years of experience. About two-thirds (66.3%) of the participants had good knowledge about antibiotic use and resistance while only 39.4% had positive attitudes. The prevalence of self-medication with antibiotics was 30%. The identified positive predictors of antibiotics self-medication included having primary education (AOR:5.874, 95%CI:1.020-33.836) compared with tertiary education, poor knowledge (AOR:1.683, 95%CI:1.015-2.789) compared with good knowledge about antibiotic use and resistance as well as negative attitude (AOR:1.861, 95%CI:1.102-3.143) compared with a positive attitude towards antibiotic use and resistance. The level of knowledge and attitude in this study was suboptimal. Self-medication was linked with a lower level of education, poor knowledge, and a negative attitude. Therefore, we recommend the provision of appropriate health education to promote the rational use of antibiotics.

Aims: Nosocomial infection is associated with increased mortality, morbidity, and length of stay. Detection of infection, identify the etiology of bacterial antibiotic resistance pattern, is necessary given the widespread use of antibiotics and antibiotic-resistant organisms. Materials and Methods: This cross-sectional study was done on 288 patients admitted to the Beheshti Hospitals in Kashan based on NNIS definitions according to the state of Health and Medical education. In this study infections and antibiotic resistance symptoms were found. Data analyses were performed with Chi-square test. Results: Among the 288 patients studied, with mean out of hospital infection was 0.80%. Most cases of infection associated were pneumonia. The highest rates of infection were in the Intensive Care Unit (ICU) with 51.7%. Nosocomial infection in ICU wards was associated with increased mortality and morbidity. The most common types were ventilator-associated pneumonia. Among the microorganisms, negative Gram was seen more. The common pathogens were including Acinetobacter, Escherichia coli, and Klebsiella. Antimicrobial resistance was generally increasing and had emerged from selective pressure from antibiotic use and transmission through health staff. Conclusion: This study showed a correlation between antibiotic use and resistance of microorganisms is significant. Hence, it seems that reducing aggressive acts and conduct hygiene education and monitoring act of antibiotics is necessary to prevent antibiotic resistance.

Antibiotics are used to both prevent and treat bacterial infections. When bacteria adapt to the use of antibiotics, antibiotic resistance develops. Antibiotic resistance develops in bacteria, not in people or other animals. Both people and animals are susceptible to infection from these germs, and their illnesses are more difficult to treat than those caused by non-resistant bacteria. Antibiotic resistance causes greater mortality, longer hospital stays and higher medical expenses. The way antibiotics are prescribed and used worldwide has to alter immediately. Antibiotic resistance will continue to pose a serious hazard even if new medications are created. Additionally, behavioral changes must focus on improving food cleanliness, hand washing, practicing safer sex and being vaccinated in order to stop the spread of diseases. This chapter discusses the history, evolution and epidemiology of antibiotic resistance, antibiotic resistance mechanisms and their methods of detection, prevention of antibiotic-resistant organisms in healthcare settings and the role of artificial intelligence in prevention of antimicrobial resistance and drug discovery.

Background Antibiotic resistance (AR) remains a global crisis. However, the literature on public awareness about antibiotic use and AR in the highland provinces of Vietnam has been constrained. This study explores the awareness of antibiotic use and resistance among general people in highland provinces in Vietnam and detects associated factors. Methods A cross-sectional study was performed in five highland provinces with 1000 households. Information about socioeconomic status and awareness regarding prescription medicine use, antibiotic use, and AR was surveyed. Multivariate logistic regression was used to identify associated factors with awareness. Results 64.2% of people were aware of prescription drugs. More than two-thirds (67.4%) of participants were aware of antibiotic use, of whom only 55.8% were aware of AR. Higher age, education, and family income were positively associated with being aware of prescription medicine, antibiotic, and AR. Females had a lower likelihood of being aware of prescription medicine (OR=0.64; 95%CI=0.45-0.90) compared to male counterparts. Those being freelancers were more likely to be aware of antibiotic resistance (OR=2.30; 95%CI=1.13-4.67) compared to those working in agriculture/fishery/forestry sector. Compared to Kinh ethnic, most ethnic minorities were less likely to be aware of prescription medicine, antibiotic, and AR. Conclusions This study showed a low awareness regarding prescription medicine, antibiotic use, and AR among public people in the highland provinces of Vietnam. Further systemic and didactic educational interventions targeting females, low education, low income, ethnic minorities, and those working in agriculture/fishery/forestry sector in this setting should be performed and evaluated to improve the awareness about antibiotic use and resistance.

Overcoming resistance.

Introduction: Antimicrobial drugs are one of the most commonly prescribed drugs in hospital. Overuse and irrational use of antimicrobials is a key factor behind rapidly spreading antimicrobial resistance in microorganisms. Use of irrational and unnecessary antimicrobials remains common in the developing countries. This study was conducted to analyze the prescription pattern of antimicrobials in the department of internal medicine of tertiary care hospital. Methods: Antimicrobials are among the most commonly prescribed drugs in hospital. Overuse and irrational use of antimicrobials is a key factor behind rapidly spreading antimicrobial resistance in microorganisms. Use of irrational and unnecessary antimicrobials remains common in the developing countries. This study was conducted to analyze the prescription pattern of antimicrobials in the department of internal medicine of tertiary care hospital. Results: The mean duration of hospitalization among the study population was 5 days. Of the 460 medicines prescribed, mostly indicated for respiratory infections, and the most common antibiotic was from the group cephalosporin 209 (69.7 %). 55 % of prescriptions include only one drug, 39 % with two drugs and 6% with three or more than three drugs. Conclusion: The mean duration of hospitalization among the study population was 5 days. Of the 460 medicines prescribed, mostly indicated for respiratory infections, and the most common antibiotic was from the group cephalosporin 209 (69.7 %). 55 % of prescriptions include only one drug, 39 % with two drugs and 6% with three or more than three drugs.

Background. An excessive use of antibiotics in human and veterinary medicine contributes to the additional selection pressure on microorganisms and leads to the rapid spread of dangerous microorganisms with an increased ability to resist numerous classes of antibiotics. Aquatic ecosystems are among the main resistance genes pools, and therefore should be subject to mandatory control. Apparently, the spread of antibiotic-resistant microorganisms depends not only on the concentration of antibiotics entering water bodies with wastewaters, but also on other qualitative characteristics of the aquatic environment. The aim of this work was to determine the correlation between the content of heavy metals (Cu, Ni, Zn, Cr) and nitrogen compounds (NO 3 , NO 2 and NH 4 ) in water and the distribution of antibiotic resistant microorganisms in research sites on the Uzh River (Ukraine) that are affected by anthropogenic impact. Based on our seasonal moni­toring during 2016–2017, which included determining the content of nitrogen compounds and heavy metals in the research sites, and as a result of the study on the microbiocenosis structure with a subsequent determination of antibiotic sensitivity of the dominant strains isolated from water samples, we conducted analysis of the correlation between the concentrations of these substances and the distribution of antibiotic resistant strains. This enabled us to identify the potential factors that contribute to the deve­lopment of antibiotic resistance in microorganisms. Material and methods . The relationship between the chemical parameters and the percentage of antibiotic-resistant microorganisms was determined using the linear Pearson’s correlation coefficient (r). Statistical data processing was performed using the software package „Microsoft Excel”. Results with a p -value less than 0.05 (р<0.05) were considered statistically significant. Results. The relationship between the level of antibiotic resistance of microorga­nisms and chemical pollution has been established. A strong correlation between excessive concentrations of Zn and elevated concentrations of Ni relative to background va­lues and increased antibiotic resistance is characteristic of the area under conditions of technogenic transformation . In the urbanised area, a relationship between an increase in antibiotic resistance and Ni concentrations was observed in the studied samples. In the agricultural area, a strong correlation between nitrogen compounds, namely nitra­tes, and an increase in antibiotic resistance of microorganisms has been established. Conclusion. The obtained results that establish a correlation between the concentrations of chemical substances in water and the activation of antibiotic resistance in microorganisms can indicate the degree of aquatic ecosystems transformation under anthropogenic impact. Thus, a comprehensive monitoring of the environmental quality of aquatic ecosystems is essential. Keywords: heavy metals, nitrogen compounds, antibiotics, aquatic ecosystems, microorganisms, antibiotic resistance

Abundant evidence suggests a relationship between antibiotic resistance and use, including animal models, consistent associations between resistance and antibiotic use in hospitals, concomitant variation in resistance as antibiotic use varies, and a dose-response relationship for many pathogen/antibiotic combinations. Much of the evidence has come from studies performed in single hospitals. Most multicentre studies on resistance have not included data on antibiotic usage. Despite this substantial body of evidence, some studies have failed to demonstrate an association between antibiotic resistance and use, suggesting other contributing factors such as cross-transmission, inter-hospital transfer of resistance, a community contribution to resistance, or a complex relationship between resistance and the use of a variety of antibiotics. A multicentre study, project ICARE (Intensive Care Antimicrobial Resistance Epidemiology), implemented in 1994 by Centers for Disease Control and Prevention and Rollins School of Public Health, Emory University, has found dramatic differences in the patterns of antibiotic usage and resistance in US hospitals. The findings suggest that antibiotic usage is the major risk factor in development of antibiotic resistance in hospitals but the relationship can be complex with additional factors involved. Understanding the problem of antibiotic resistance in a hospital cannot be achieved without knowledge of the hospital's pattern of antibiotic use.

Background and Aim: Antimicrobial resistance (AMR) is one of the most pervasive health concerns worldwide in veterinary and human medicine. The inadequate use of antibiotics in the veterinary sector has contributed to antibiotic resistance (ABR), which negatively affects animal and human health. This study aimed to evaluate awareness about knowledge, attitude, and practice concerning the use of antibiotics and AMR among veterinarians and other practitioners in the field of animal health in the Wasit Governorate of Iraq. Materials and Methods: This study included 129 veterinarians and animal health workers from various areas of Wasit Governorate (Suwayra, Numaniyah, Kut, and Al-Hai) in eastern Iraq, southeast of Baghdad. Participants’ personal information (age, sex, education, employment history, region, workplace, and current position) and knowledge, attitudes, and behaviors regarding antibiotic usage and resistance were collected using a questionnaire. The Statistical Analysis System (SAS, 2018) was used to analyze the data. Results: Based on 16 knowledge evaluation questions, only 43.75% had good knowledge, and 56.25% had fair to poor knowledge of antibiotic usage and AMR. There is a lack of understanding of the threat of treatment-resistant bacteria (34.88%). Similarly, there are some gaps in the understanding of the link between efficient management procedures in agriculture and the prevention of resistance development (36.43%). As per the 13 attitude questions, this research found that only 38.46% of the participants had a positive view on antibiotic usage and ABR, while the rest of 61.54% had a neutral view. High rates of participants (80.62%) considered it of great importance to provide sufficient antibiotic doses, proper management, immunization, and the use of animal antibiotics only when necessary and with veterinary assistance. Based on the six questions, our research found that half of the participants had excellent practices regarding antibiotic usage and resistance, whereas the other half had poor to moderate habits. There was a highly significant correlation (p ≤ 0.01) between the knowledge and attitude of the participants in this study, as well as a significant correlation (p ≤ 0.05) between the knowledge and practices and between the attitudes and practices of the participants. Conclusion: Participants’ compliance was poor despite having moderate knowledge of antibiotic use and AMR. Implementing educational and training programs may enhance veterinarians and animal health workers’ understanding, attitude, and behavior. Keywords: antimicrobial resistance, antimicrobial stewardship, knowledge, attitude, and practice, veterinary profession, Wasit province.