Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role of One Health

*Istifanus Anekoson Joshua, Mathew Bobai and Clement Sokfa Woje*

## **Abstract**

Infections caused by micro-organisms affect the health of people and animals, causing morbidity and mortality, with Asia and Africa as the epicenters. Some of the infectious diseases are emerging and re-emerging in nature. Examples include viral hepatitis, Lassa fever, Ebola, yellow fever, tuberculosis, covid-19, measles, and malaria, among others. Antimicrobials have been playing an important role in the treatment of infections by these microbes. However, there has been a development of resistance to these antimicrobials as a result of many drivers. This write-up used secondary data to explore the management of antimicrobial resistance (AMR) beyond the hospital antimicrobial resistance steward using the one health concept. The findings showed AMR to be a transboundary, multifaceted ecosystem problem affecting both the developed and developing countries. It is also one of the top ten global public health threats facing mankind. Globally, AMR will cost over US\$100 trillion in output loss by 2050, about 700,000 deaths a year, and 4,150,000 deaths in Africa by 2050. About 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain AMR. The drivers of AMR are beyond the hospital and hospital AMR stewardship. Therefore, the need for one health concept to manage it.

**Keywords:** antimicrobials, antimicrobial resistance, Hospital antimicrobial stewardship, infections, one health

## **1. Introduction**

Infectious diseases are caused by microbes such as bacteria, viruses, fungi, or parasite, which often affect human and animal health. The mode of transmission can be direct, such as spread from person to person, or indirect contact via insect bites, food and water contaminations, among others [1].

Africa with the fastest growing population in the world, is now catching up with Asia as infectious diseases hotspot [2]. Infectious diseases have accounted for about one-quarter of deaths, and are globally responsible for at least ten million deaths annually, especially in tropical countries at the beginning of the 21st century. Some of the infectious diseases are emerging while some are re-emerging in nature. Examples of these diseases reported in Africa include meningococcal meningitis, hepatitis B, C, and E viruses, tuberculosis, Dengue fever, Lassa fever, yellow fever, Ebola virus, COVID-19, measles, HIV/AIDS, plague, avian influenza, chikungunya, syphilis and poliomyelitis, monkey pox, Marburg virus, Zika virus, rift valley fever, malaria, cholera, rickettsia, among others (**Table 1**).


#### **Table 1.**

*Some emerging and re-emerging infectious diseases reported in Africa [3–13].*

#### *Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

The burden of infectious diseases in Africa is huge, and it has topped the list of diseases that frequently require consultation, hospitalization and also remain a major cause of morbidity and mortality. Antimicrobials play important roles in their treatment, emergence of resistance, persistence, and transmission. They have also saved hundreds of millions from infectious agents. However, antimicrobial resistant (AMR) organisms are increasing globally, threatening to render existing treatments ineffective. They prolong illness, increase case fatality, facilitate transmission, and increase treatment costs.

Antimicrobial resistance caused by bacteria and viruses are of greater public health significance. This is because they account for a large share of clinical infections observed. Their emergence has compromised the effectiveness of antimicrobials [14]. The use of antibiotics makes them serve as reservoirs of resistant genes with the propensity to spread via ecological niche through the human, animal, and environmental interactions [15, 16].

Some factors associated with antimicrobial resistance include microbial adaptation and change, human susceptibility to infection, poor environmental practices, human demographics and behavior, international travel and commerce, technology and industry, breakdown of public health measures, poverty and social inequality, war, and famine and lack of political will [3].

## **2. Antimicrobials and antimicrobial resistance**

Antimicrobials are global public good that has improved health care, saved lives, and enhanced economic gains [17]; and they are the cornerstone on which the health system is standing on [18]. Antimicrobial resistance is the alteration of microbes when exposed to the antimicrobial making them not sensitive. These drugs become ineffective and infections persist in the body, increasing the risk of spread to others.

Antimicrobial resistance is the development of resistance in a microorganism to an antimicrobial agent to which it was previously sensitive [19]; and it is a multifaceted ecosystem problem that threatens the interdependent humans, animals, and environmental health [15, 20]. In view of this importance, the World Health Organization theme for 2011 was tagged "antimicrobial resistance: no action taken, no cure tomorrow".

## **3. Magnitude of the problem of antimicrobial resistance**

The World Health Organization (WHO) has declared that antimicrobial resistance is one of the top ten global public health threats the world is battling with [4]. Antimicrobials such as antibacterial, antivirals, antifungals, and antiparasitics are used to prevent and treat infections in human, animals and plants [4].

United Nations General Assembly, World leaders of G7 and G20, and WHO declared AMR as a global health security challenge today. It is a transboundary problem that concerns every country irrespective of its level of income and development, where the organisms require no international passports [15, 20]. Antimicrobial resistance is a global crisis that risks reversing a century of progress in health [21]. Alarming levels of resistance have been reported in both developing and developed countries, with the result that common diseases are becoming untreatable, and lifesaving medical procedures more at risk to perform [21].

Antimicrobial resistance is also an ecosystem problem threatening the interrelated human-animal-environment health under the "One Health" framework. Resistant bacteria arising in one geographical area can spread via cross-reservoir transmission to other areas worldwide either by direct exposure or through the food chain and the environment [22, 23]. Sixty percent of pathogens harmful to humans are of animal origin; humans and animals share the same bacteria [17].

The economic burden of AMR is difficult to calculate due to insufficient data and the need to account for externalities, especially in Africa [24]. Globally, drug-resistant microbes account for at least 700,000 yearly deaths and 230,000 deaths from resistant mycobacteria are projected to increase to 10 million deaths globally by 2050 in no action is taken. Around 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain antimicrobial resistance [21]. Estimates of the impact of AMR on the US economy are exceedingly high, including \$20 billion in direct health care costs with additional indirect costs as high as \$25 billion, 2 million illnesses, and 23000 deaths per year [25].

The World Bank projected that 24 million people could fall into extreme poverty by 2030 because of AMR and most would come from low- and middle-income countries [15]. Globally, AMR will cost over US\$100 trillion in lost output by 2050 [23] and about 4,150,000 deaths in Africa by 2050 [19, 23]. The problem of AMR is global but is particularly more serious in sub-Saharan Africa, second only to that of Asia.

The increase in AMR could lead to a reduction in options available to treat infectious diseases, support chemotherapy, and surgery, and this will have a significant impact on the Health System and economies [19]. Infections with resistant organisms have been associated with an increased hospital stay, increased morbidity and mortality, use of additional drugs, laboratory tests, and increased treatment cost [26, 27]. This has financial implications for the individuals, families, communities, and the health system (HS) [19]. This has increased poverty as it has been documented that millions of Africans fall into poverty due to high out-of-pocket health payments [28]. Antimicrobial resistance could lead to loss of productivity from the spread of diseases to other animals and death of the animals, thereby threatening the sustainability and security of food production and the livelihood of farmers. The proportion of antimicrobials resistance has at least doubled in chickens and in pigs in the past two decades [25].

Reports have identified significant gaps in surveillance, standard methodologies, and data sharing related to AMR; and Africa and South East Asia as regions without established AMR surveillance systems [29]. This results in a lack of quality data leading to treatment guidelines that are not adequate for the local situation. Consequently, the rise and spread of AMR threaten the effective control and treatment of various bacterial diseases world wide [15, 20]. In addition, the lack of consistency in the measurement and reporting of susceptibility data makes it difficult to compare findings among different countries and laboratories, sometimes even within one country [30].

Infections caused by antimicrobial resistance are now alarming globally, and the increasing rates of antimicrobial resistance are resulting in fewer treatment options [31]. The world's known antimicrobials are becoming increasingly ineffective as drug resistance spreads globally leading to more difficult to treat infections and deaths [4]. The problem is further compounded by the fact that very few new antibiotics have been developed within the last thirty years. We effectively do not have any new weapon in the fight against AMR. Therefore, new antimicrobials are urgently needed to treat especially carbapenem-resistant gram-negative bacterial infections as identified by the WHO priority pathogen list [4].

*Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

Without effective tools for the prevention and adequate treatment of drugresistant infections, the maternal number of death due to drugs resistant infections will increase, and medical procedures such as surgery, including cesarean sections, hip replacements, cancer chemotherapy, and organ transplantation will become riskier [4].

Statistics indicated that malaria claims more than one million lives yearly, and African countries bear the brunt of malaria accounting for more than 90% of all cases occurring worldwide [32]. In Africa, malaria has devastating consequences on agricultural households. It is estimated that malaria cost Africa more than twelve billion United State dollar per year slowing its economic growth by 1.3% annually [33]. Tuberculosis is one of the top leading causes of mortality globally and the highest incidence rates are found in Africa and south-east Asia [34].

HIV/AIDS kills and disable adults in the productive part of their lives affecting businesses, investments, industries, agricultural sustainability, and African agricultural labor force in particular affected [35]. It is worth noting, that bacterial diarrhea, malaria, tuberculosis, and HIV infections, responsible for high mortality rates in sub-Saharan Africa, are also showing increased resistance to hitherto effective antimicrobials. *Candida auris* has shown increased resistance to antifungal drugs such as fluconazole, amphotericin B, Voriconazole, among others [4]. In Nigeria, there is a widespread antimicrobial resistance among enteric *Escherichia coli*, particularly to penicillins, aminoglycosides, cephaloporins, chloramphenicol, tetracycline, and cotrimoxazole [36].

## **4. Drivers of antimicrobial resistance transmission**

Antimicrobial resistance is complex, multi-sectoral and a cross-boundary challenge being driven by clinical, biological, social-political, economical, and environmental drivers and exerts effect not only on humans, but also animals and the ecosystem. However, the key drivers of antimicrobial resistance include poverty, lack of access to clean water, sanitation, and hygiene for both human and animals; poor infections and diseases prevention and control in healthcare facilities and farms; changing population density; poor management of pharmaceutical and hospital wastes; antibiotic misuse and overuse; poor access to quality and affordable medicines, vaccines, and diagnostics; poor public knowledge about antimicrobials and its resistance; lack of enforcement of legislation; lack of surveillance systems; lack of food safety and control measures; poor environmental practices, poor documentation of AMR in animals, poor evidence-based data on the magnitude and economic burden of AMR in humans; poor rules and regulations to control counterfeit drugs in the market and unique transmission properties of antimicrobial resistant organism, chemical stressors in an environment, among others [37].

Bacteria usually adopt some mechanisms to resist antibiotic action against them. These mechanisms include the inactivation of the antibiotic through enzymatic degradation, or modification of the antibiotic targets, alteration of the permeability of the cell membrane, and the expression of efflux pumps to keep intracellular of antibiotic below inhibitory level [37].

Several unique properties of antimicrobial resistant bacteria enable their development and propagation in the environment. Autochthonous bacteria constitute environmental reservoirs of antibiotic resistance genes or "resistomes" that can subsequently be transferred to pathogens via horizontal gene transfer (HGT) [37, 38]. This

HGT can occur through conjugation, transduction or transformation. However, the key global concern is the development of resistance of last resort, such as the cephalosporins, carbapenems, and polymyximises [39]. Resistance to third-generation cephalosporins has increased worldwide to bacterial acquisition of the ability to produce extended-spectrum beta-lactamase enzymes (ESBL) that mediate resistance to most beta – lactams [40]. Bacteria and mobile genetic elements conferring resistance linger on animal skin and in feces and by various means can be transferred between bacteria, and these organisms can make their way to human beings [41]. Evidence of transmission from livestock to human beings ESBL and AmpC – B – Lactamase genes on plasmids and *Escherichia coli* clones, most likely through the food chain have been reported [41].

### **4.1 Environmental and related factors**

In developing countries with scarce resources, poor sanitation, poor food safety measures, sales of antimicrobial over the counter, overcrowding, use of antimicrobials in animal and fish farming, and weak government regulations are some of the leading causes of antimicrobial resistance [42, 43]. There has been documentation of antibiotics being added directly to dairy products by vendors in order to increase shelf-life in Ethiopia [44]. Others showed high antimicrobial residues in eggs and meat in Nigeria [45], Ghana [46], Senegal [47], Kenya [48], and Tanzania [49].

### **4.2 Changing of population density**

Movement of people from rural to urban areas (urbanization) brings considerable negative and positive changes in their living and working conditions. In the urban areas, housing density increases, there is overcrowding, animals and humans may share dwelling places and drinking water, among others with resultant negative health consequences. One of the problems associated with rural-urban migration of people includes AMR infection transmission, which has been documented [50].

#### **4.3 Use of antimicrobials in human and veterinary medicine**

Antimicrobial are among the most commonly prescribed drugs in human and veterinary medicine but about 50% of these are considered unnecessary [51]. This is associated with misuse, overuse, and underuse especially in low, middle, and highincome countries (LMIC) [52, 53]. These consumptions could be a major driver of AMR. When antibiotics are used, either for medicinal purposes or for food animal production, they inevitably make their way into the environment [40].

Antibiotics have been in use in livestock, cattle, and aquaculture, among others to enhance production and growth for human consumption. A study showed that among different countries using veterinary antibiotics, Myanmar, Indonesia, Nigeria, Peru, and Vietnam have been projected to have the greatest increase by 2030 in that descending order [54].

Treatment of ailing fish with antibiotics used for human medicine and then dumping these treatments directly into the water or via fish food is one of the leading causes of bacterial resistance in the aquatic environment. Substantial evidence supports the link between antibiotic resistance in livestock and the emergence of bacterial resistance in humans [55, 56].

*Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

### **4.4 Counterfeit antibiotics**

Counterfeit antibiotics are a type of substandard drug and the influx into the global pharmaceutical market is estimated at 5% [57]. The majority of these products originating from south-East-Asia and Africa, are destined mainly for emerging countries including South-East –Asia, sub-Saharan Africa, Europe, and North America [57]. Even though it is a worldwide problem, it is still not eradicated and it continues to exert a devastating negative impact mainly because of poverty, globalization, ease of international trade, the lack of regulations, and law enforcement, among others.

## **4.5 Non-prescription antibiotics**

Globally, antibiotics are becoming more and more available over-the-counter or via unregulated supply chains [58, 59], which is a problem in both developing and developed countries [60]. This results from weak law enforcement or even the absence of policies and regulations [61]. In developing countries mainly Africa, the community is providing different unauthorized services like consulting, diagnosing, prescribing, and dispensing medications [62]. These illegal practices if no care is taken can increase selection pressure and consequently AMR.

## **5. Overview antimicrobial and hospital antimicrobial stewardship**

Antimicrobial stewardship is the effort to measure and improve how antimicrobials are prescribed by clinicians and used by patients. Improving antimicrobials prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antimicrobial use, and combat antimicrobial resistance. (www.cdc.gov/antibiotic-use/core-elements/index.html).

CDC's Core Elements of Antibiotic Stewardship offers providers and facilities a set of key principles to guide efforts to improve antibiotic use and, therefore, advance patient safety and improve outcomes. These frameworks complement existing guidelines and standards from key healthcare partner organizations, including the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, American Society of Health System Pharmacists, Society of Infectious Diseases Pharmacists, and The Joint Commission (CDC www.cdc.gov/antibiotic-use/ core-elements/index.html).

It is the use of standard antibiotic regimens for the treatment of infections thus optimization of antibiotic use. This program has been implemented in some countries with impressive results [48], leading to a reduction in the use of antibiotics especially broad-spectrum antibiotics in addition to a decrease in healthcare costs and the improvement of patient outcomes and AMR containment [63, 64]. Similar programs in South Africa, a lower-middle-income country, in both the private and public hospital sectors, have shown reductions in inappropriate antibiotic use, among others [65].

The Core Elements of Hospital Antibiotic Stewardship Programmes [66] include:


## **6. Deficiencies in the hospital antimicrobial stewardship program**

Because the drivers of antimicrobial resistance lie in humans, animals, plants, food, and the environment (i.e., beyond the hospital), a sustained One Health response is essential to engage and unite all stakeholders around a shared vision and goals.

Human resources for health (HRH) are key in the hospital antimicrobial resistance containment. However, inadequate and inequity in the distribution of health workers is a huge problem, especially in Africa, and Nigeria [67]. The maldistribution of health workforces is central to the existing inequalities in health service coverage and the burden of disease for populations in need.

Weak health system: Although the battle of AMR is a global one, Africa is currently at a disadvantage in the fight because of weak healthcare systems and other factors that are slowing the continent's efforts in the fight. This will have serious negative human, social, economic, and developmental consequences in the region [15]. Africa is a continent bellied with challenges such as widespread poverty, armed conflicts, high level of illiteracy, poverty, and very weak medical and veterinary health institutions [68], that have made the continent poorly prepared to effectively fight this public health threat.

## **7. The role of One Health**

One Health is an approach of multiple disciplines working locally, nationally, and globally to obtain better health for people, animals, and the environment. It has the potential to mitigate the negative externality of AMR [69].

Studies have shown that implementing one health, especially in low-income countries will save lots of money for the veterinary and medical health systems [44, 68]. This money can be used to enhance surveillance and improve capacities in medical and veterinary HS. Surveillance systems are the foundation for a better understanding of the epidemiology of AMR and the key for tackling this public health threat [46].

*Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

#### **7.1 The benefits of One Health in tackling antimicrobial resistance**

Tackling antimicrobial resistance from the "One Health" perspective is emaced by the WHO/FAO/OIE Tripartite, the Declaration from the 2016 high-level meeting on antimicrobial resistance at the United Nations General Assembly, and is supported by the World Bank [20, 70, 71]. This model engenders broad effectiveness and efficiency outcomes generating savings in operating costs. It is based on building veterinary/ human public-health capacity and enhancing awareness in order to reach effective global governance. Capitalizing on these capacities or reducing the vulnerabilities, especially in low-income countries will prevent or mitigate the leading causes of antimicrobial resistance and infectious pandemic.

The adoption and implementation of laboratory-based surveillance and monitoring system in the African WHO regional office is poor. In LMICs, the challenges are enormous due to weak laboratory and communications infrastructure, lack of trained and qualified staff, and higher incidence of counterfeit antibiotics [72]. Current surveillance capabilities are variable across the world. Europe and the USA have the best surveillance coverage while Sub-Saharan Africa, South and Southeast Asia have the least developed [51]. Therefore, there is need for global public health awareness on the importance of rational antibiotic use and emergence of resistance.

## **8. Conclusion**

The importance of antimicrobial resistance cannot be neglected in view of its consequences globally, regionally, nationally, and locally. It is a hazard that must be prevented and/or mitigated. Health Education of the general population and clinicians on wrong antibiotic choice, wrong dose, wrong dose interval, wrong route, wrong duration, and delayed administration could be helpful.

Multimodal strategies for the control of AMR, Research and Development, environmental control, market control, and manufacturing should be explored.

Establishment of laboratory for human and animal diseases research: Adequate funding is critical; however, the sources of funding can be from governmental and non-governmental entities.

Surveillance of antibiotic consumption in medical and veterinary medicine is fundamental; and a massive global public awareness is important to enhance knowledge about AMR in general and antibiotic uses and resistance in particular. Surveillance systems are the foundation for a better understanding of the epidemiology of AMR and the key for tackling this public health threat.

Medical prescriptions should be based on the local antibiogram. There is a need to explore alternatives to antimicrobials, such as phages and probiotics, among others.

## **Acknowledgements**

I sincerely acknowledge my teachers, namely Professors JKP Kwaga, Junaidu Kabir, TO Aken'Ova, Clara Ladi Ejembi, Kabir Sabitu, Mohammed Bello, and Dr FJ Giwa of Ahmadu Bello University, Zaria, Nigeria.

Others are Late Professors Andrew Nok, James Adagadzu Kagbu and Stephen Nkom, Late Dr TT Gbem and Late Colonel (Dr) Chinedu John Camillus Igboanusi, Yahuza Suleiman, Bawa Egga, Eunice Azimheye Mamedu, and Esther Jonah.

I also acknowledge Mrs Wazi Istifanus, Ovye Istifanus, Ahogbresha Istifanus, Ashe-ulu Istifanus, and Abesla Istifanus for all their support.

## **Conflict of interest**

The authors declare no conflict of interest.

## **Author details**

Istifanus Anekoson Joshua1 \*, Mathew Bobai2 and Clement Sokfa Woje1

1 Department of Community Medicine, Faculty of Clinical Sciences, College of Medicine, Kaduna State University, Kaduna, Nigeria

2 Department of Microbiology, Faculty of Science, Kaduna State University, Kaduna, Nigeria

\*Address all correspondence to: dristifanus@yahoo.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

## **References**

[1] Gerald LM, John EB, Raphael D, Mandell D. Bennett Principle and Practice of Infectious Diseases. 7th Edition. Philadelphia, USA: Churchill Living Stone, Elsevier Limited. 2010

[2] Bornard B, Delia R, John M. Africa's Growing Risk of Diseases that Spread from Animals to People, 2020. IFFRI blogi - issue. Available at: https//www. iffri.org/blogi/africas-growing-riskdisease-spread-animals-people [Accessed on 26 January, 2022]

[3] Fenollar F, Mediannikov O. Emerging Infectious Diseases in Africa in the 21st century. Philadelphia, USA: Elsevier Ltd. 2018

[4] WHO. Antimicrobial Resistance. 2021. Available at https://www.who. int/news.room/fact.sheet/details/ antimicrobialresistance [Accessed 20th January, 2022]

[5] Carey EM, Steele DA. The severe Typhoid fever in Africa program highlights the need for broad deployment of typhoid conjugate vaccine. Clinical Infections Diseases. 2019;**69**(6):S413-S416

[6] Marks F, Kalckreuth V, Aaby P, Adu-Sarkodie YJ, El-Tayeb MA, Ali M, et al. Incidence of Invasive *Salmonella* Disease in sub-Saharan Africa: A multicentre population-based surveillance study. The Lancet Global Health. 2017;**5**(3):e310-e323

[7] Mourembou G, Lekana-Douki JB, Mediannikov O, Nzondo SM, Kouna LC, Essone JC, et al. Possible role of Rickettsia felis in acute febrile illness among children in Gabon. Emerging Infectious Diseases. 2015;**21**:1808-1815

[8] Sands P, Mundaca-Shah C, Dzau VJ. The neglected dimension of global Security a framework for countering infectious-disease crises. The New England Journal of Medicine. 2016;**374**:1281-1287

[9] Federal Ministries of Agriculture Environment and Health (FMAEH). Antibacterial Use and Resistance in Nigeria: Situation Analysis and Recommendations. 2019. pp. 12-158

[10] Noah K, Jeffrey DK. An update on the global epidemiology of Syphilis. Current Epidemiology Records. 2019;**5**(1):24-28. DOI: 10.1007/ s40471-018-0138-2

[11] WHO. Trypanosomiasis, Human African (sleepy sickness), 2022. www. who.int'l…factsheets,detail [Accessed 19 February, 2022]

[12] Eliberiki RM, Sol H, Robert F, Hezron EN, Robinson HM, Eystein S. Anthrax outbreaks in the humans-livestock and wildlife interface areas of Northern Tanzania: A Retrospective Record Review*,* 2006-2016. BMC Public Health. 2018;**18**(106):2018

[13] Richard M, Notion TG, Tapuwa M, Mufuta T. Investigation of an Anthrax outbreak in Makoni district, Zimbabwe. BMC Public Health. 2021;**21**(298):2021

[14] Presi P, Stärk KD, Stephan R, Breidenbach E, Frey J, Regula G. Risk scoring for setting priorities in monitoring of antimicrobial resistance in meat and meat products. International Journal of Food Microbiology. 2009;**130**:94-100

[15] World Bank Group. Operational Framework for Strengthening Human, Animal, and Environmental Public Health Systems at Their Interface; International Bank for Reconstruction and Development/The World Bank: Washington, DC, USA, 2018

[16] Iskandar K, Molinier L, Hallit S, Sartelli M, Catena F, Coccolini F, et al. Drivers of antibiotic resistance transmission in low and middleincome countries from a "One Health" perspective—A review. Antibiotics. 2020;**9**:372

[17] Koch BJ, Hungate BA, Price LB. Food-animal production and the spread of antibiotic resistance: The role of ecology. Frontiers in Ecology and the Environment. 2017;**15**:309-318

[18] European Food Safety Authority; European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2016. EFSA Journal. 2018;**16**:e05182

[19] Machado AR, Pinho DB, de Oliveira SA, Pereira OL. New occurrences of Botryosphaeriaceae causing black root rot of cassava in Brazil. Tropical in Plant Pathology. 2014;**39**:464-470

[20] White A, Hughes JM. Critical importance of a one health approach to antimicrobial resistance. EcoHealth. 2019;**16**:404-409

[21] No time to wait: Securing the future from drug-resistant infections; Report to the Secretary-General of United Nations, April, 2019. ww.who.int/ antimicrobial-re-sistance/interagencycoordination-group/IACG\_final\_summary\_EN.pdf?ua=1 United Nations. Political Declaration of the High-level Meeting of the General Assembly on Antimicrobial Resistance, A/71/L.2. [Accessed 22 September, 2016]

[22] Holmes AH, Moore LS, Sundsford A, Steinbakk M, Regmi S, Karkey A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 2016;**387**:176-187

[23] McEwen SA, Collignon PJ. Antimicrobial resistance: A One Health perspective. Microbiology Spectrum. 2018;**6**:521-547

[24] Wright GD. The antibiotic resistome: The nexus of chemical and genetic diversity. Nature Reviews. Microbiology. 2007;**5**:175

[25] Van Hoek AH, Mevius D, Guerra B, Mullany P, Roberts AP, Aarts HJ. Acquired antibiotic resistance genes: An overview. Frontiers in Microbiology. 2011;**2**:203

[26] Essack SY, Connolly C, Sturm AW. Antibiotic use and resistance in publicsector hospitals in KwaZulu-Natal. South African Medical Journal. 2005;**95**:865-870

[27] Agyepong N, Govinden U, Owusu-Ofori A, Essack SY. Multidrug-resistant gram-negative bacterial infections in a teaching hospital in Ghana. Antimicrobial Resistance and Infection Control. 2018;**7**:37

[28] Ramsamy Y, Mlisana KP, Allam M, Amoako DG, Abia AL, Ismail A, et al. Genomic analysis of carbapenemaseproducing extensively drug-resistant Klebsiella pneumoniae isolates reveals the horizontal spread of p18-43\_01 plasmid encoding blaNDM-1 in South Africa. Microorganisms. 2020;**8**:137

[29] World Health Organization (WHO). Antimicrobial Resistance Global Report on Surveillance. Geneva: WHO; 2014

[30] Cox G, Wright GD. Intrinsic antibiotic resistance: Mechanisms, *Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

origins, challenges and solutions. International Journal of Medical Microbiology. 2013;**303**:287-292

[31] Schwarz S, Loeffler A, Kadlec K. Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine. Veterinary Dermatology. 2016; **28**(1):82-e19

[32] Ruxin J, Palizzi JE, Wilson PA, Tozan Y, Kruk M, Teklehaimanot A. Emerging consensus in HIV/AIDS, Malaria, Tuberculosis and access to essential medicines. The Lancet. 2005;**365**(9459):618-621

[33] Bartram J, Lewis K, Kenton R, Wright A. Focusing on improved water and sanitation for health. The Lancet. 2005;**365**(9461):810-812

[34] Laxminarayan R, Klein E, Dye C, Floyd K, Dareley S, Adeyi O. Economic Benefit of Tuberculosis Control. Washington, DC: The World Bank; 2007

[35] UNAIDS. The impact of AIDS on people and Societies 2006. Available at htt://data.UNAIDS.org [Accessed 20th January, 2022]

[36] Fagbamila IO, Barco L, Mancin M, Kwaga J, Ngulukun SS, Zavagnin P, et al. Samonella serovars and their distribution in Nigerian Commercial chicken layer farms. PLoS One. 2017;**12**(3):e0173097

[37] Vikesland P, Garner E, Gupta S, Kang S, Maile-Moskowitz A, Zhu N. Differential drivers of antimicrobial resistance across the world. Accounts of Chemical Research. 2019;**52**:1916-1924

[38] D'Costa VM, McGrann KM, Hughas DW, Wright GD. Sampling the antibiotic resistome. Science. 2006;**311**:374-377

[39] Johnson AP, Woodford N. Global spread of antibiotic resistance: The example of New Delhi Metallo-B-Lactamase (NDM) - mediated Carbapenem resistance. Journal of Medical Microbiology. 2013;**62**:499-513

[40] Aliison HH, Luke SPM, Arnfinin S, Martin S, Sadie R, Abhilasha K, Philippe JG. Laura JPP. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 2016;**387**:176-187

[41] Pal C, Bentsson-Palme J, Kristansson E, Larsson DGJ. The structure and diversity of human, animal and environmental resistomes. Microbiome. 2016;**4**:54

[42] Rousham EK, Unicomb L, Islam MA. Human, animal and environmental contributors to antibiotic resistance in low-resource settings: Integrating behavioural, epidemiological and One Health approaches. Proceedings of the Royal Society B: Biological Sciences. 2018;**285**:20180332

[43] Nadimpalli M, Delarocque-Astagneau E, Love DC, Price LB, Huynh BT, Collard JM, et al. Combating global antibiotic resistance: Emerging one health concerns in lower-and middle-income countries. Clinical Infectious Diseases. 2018;**66**:963-969

[44] Carruth L, Roess AA, Terefe Y, Hosh FM, Salman MD. Antimicrobial resistance and food safety in Africa. The Lancet Infectious Diseases. 2017;**17**:575-576

[45] Kabir J, Umoh VJ, Audu-Okoh E, Umoh JU, Kwaga JKP. Veterinary drug use in poultry farms and determination of antimicrobial drug residues in commercial eggs and slaughtered chicken in Kaduna State, Nigeria. Food Control. 2004;**15**:99-105

[46] Donkor ES, Newman MJ, Tay SC, Dayie NT, Bannerman E, Olu-Taiwo M. residues contaminating meat and egg in Ghana. Food Control. 2011;**22**:869-873

[47] Abiola FA, Diop MM, Teko-Agbo A, Delepine B, Biaou FC, Roudaut B, et al. Résidus d'antibactériens dans le foie et le gésier de poulets de chair dans les régions de Dakar et de Thiès (Sénégal). Revista Médicina véterinaria. 2005;**156**:264-268

[48] Kangethe EK, Aboge GO, Arimi SM, Kanja LW, Omore AO, Mcdermott JJ. Investigation of risk of consuming marketed milk with antimicrobial residues in Kenya. Food Control. 2005;**16**:349-355

[49] Kurwijila LR, Omore A, Staal S, Mdoe NSY. Investigation of the risk of exposure to antimicrobial residues present in marketed milk in Tanzania. Journal of Food Protection. 2006;**69**:2487-2492

[50] Sun MM, Ye M, Schwab AP, Li X, Wan JZ, Wei Z, et al. Human migration activities drive the fluctuations of ARGs: Case study of Landfills in Nanjing, Eastern China. Journal of Hazard Materials. 2016;**315**:93-101

[51] World Bank. Drug-Resistant Infections: A Threat to Our Economic Future. Washington, DC: World Bank; 2017

[52] Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States. Atlanta: CDC; 2013

[53] World Health Organization. The Evolving Threat of Antimicrobial Resistance: Options for Action. Geneva, Switzerland: World Health Organization; 2012

[54] Van Boeckel TP, Pires J, Silvester R, Zhao C, Song J, Criscuolo NG, et al.

Global trends in antimicrobial resistance in animals in low-and middle-income countries. Science. 2019;**365**:eaaw1944

[55] Chatterjee A, Modarai M, Naylor NR, Boyd SE, Atun R, Barlow J, et al. Quantifying drivers of antibiotic resistance in humans: A systematic review. The Lancet Infectious Diseases. 2018;**18**:e368-e378

[56] European Centre for Disease Prevention and Control (ECDC); European Food Safety Authority (EFSA); European Medicines Agency (EMA). ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals: Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report. EFSA Journal. 2017;**15**:e04872

[57] Delepierre A, Gayot A, Carpentier A. Update on counterfeit antibiotics worldwide; public health risks. Médecine et Maladies Infectieuses. 2012;**42**:247-255

[58] Okeke IN, Lamikanra A, Edelman R. Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries. Emerging Infectious Diseases. 1999;**5**:18

[59] Byarugaba DK. Antimicrobial resistance in developing countries and responsible risk factors. International Journal of Antimicrobial Agents. 2004;**24**:105-110

[60] Guinovart MC, Figueras A, Llor C. Selling antimicrobials without prescription\_ far beyond an administrative problem. Enfermedades Infecciosas Y Microbiologia Clinica (Engl. Ed.). 2018;**36**:290-292

[61] Auta A, Hadi MA, Oga E, Adewuyi EO, Abdu-Aguye SN, Adeloye D, *Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role… DOI: http://dx.doi.org/10.5772/intechopen.104170*

et al. Global access to antibiotics without prescription in community pharmacies: A systematic review and meta-analysis. The Journal of Infection. 2019;**78**:8-18

[62] Kwena Z, Sharma A, Wamae N, Muga C, Bukusi E. Provider characteristics among staff providing care to sexually transmitted infection self-medicating patients in retail pharmacies in Kibera slum, Nairobi, Kenya. Sexually Transmitted Diseases. 2008;**35**:480-483

[63] Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010- 2011. JAMA. 2016;**315**:1864-1873

[64] Brink AJ, Messina AP, Feldman C, Richards GA, Becker PJ, Go DA, et al. Antimicrobial stewardship across 47 South African hospitals: An implementation study. The Lancet Infectious Diseases. 2016;**16**:1017-1025

[65] Brink AJ, Messina AP, Feldman C, Richards GA, van den Bergh D. Netcare Antimicrobial Stewardship Study Alliance. From guidelines to practice: A pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals. The Journal of Antimicrobial Chemotherapy. 2017;**72**:1227-1234

[66] Elements of Hosp AMS- Centres for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs; US Department of Health and Human Services. Atlanta, GA, USA: CDC; 2014

[67] World Health Statistics. Monitoring Health for Sustainable Development. World Health Oganisation. Geneva, Switzerland. 2021

[68] Joshua IA, Bauche J, Abdulla S. Managing Antimicrobial Resistance from Medical and Veterinary Health Systems Perspectives to Achieving Universal Health Coverage in the African Region (Review Article). SEEJPH 2021, posted: 18 May 2021. DOI: 10.11576/seejph-4446

[69] Laxminarayan R, Chaudhury RR. Antibiotic resistance in India: Drivers and opportunities for action. PLoS Medicine. 2016;**13**:e1001974

[70] Aidara-Kane A, Angulo FJ, Conly JM, Minato Y, Silbergeld EK, McEwen SA, et al. World Health Organization (WHO) guidelines on use of medically important antimicrobials in food-producing animals. Antimicrobial Resistance and Infection Control. 2018;**7**:7

[71] World Health Organization. Ten Threats to Global Health in 2019. Geneva, Switzerland: World Health Organization; 2019

[72] Coulter S, Merollini K, Roberts JA, Graves N, Halton K. The need for costeffectiveness analyses of antimicrobial stewardship programmes: A structured review. International Journal of Antimicrobial Agents. 2015;**46**:140-149

## **Chapter 5**
