**Abstract**

Antimicrobial resistance (AMR) has been a public health threat globally, with millions of lives lost due to AMR infections each year. The cases of AMR continue to escalate and cause devastating effect to both humans and animals. AMR contributes to high morbidity and mortality of the livestock, which results in staggering economic losses to the livestock producers. The main factor for AMR to arise in this industry is mainly due to the eagerness of livestock producers to meet high demand by using antimicrobials to promote animal growth and disease prevention. From a public health perspective, AMR in dairy cattle can also jeopardize human population due to the potential dissemination of AMR pathogens to humans via consumption of infected dairy products or direct contact with infected dairy cattle. At the current rate of unrestricted antimicrobial usage, AMR will be expedited and soon we will run out of effective treatment for even the simplest infection. World Health Organization (WHO) has issued a set of guidelines for the use of medically important antimicrobials on animals to mitigate the adverse consequences of AMR on human. Thus, this chapter will explain antimicrobial usage in dairy cattle production and the recent approaches and challenges on AMR.

**Keywords:** antimicrobial resistance, antimicrobial usage, dairy cattle, antimicrobial, one health

#### **1. Introduction**

AMR is undoubtedly one of the greatest health threats perceives by mankind. It causes increased morbidity, mortality and social and economic burdens [1–4]. For decades, antimicrobials were used not only in treating humans but also in veterinary medicine, agriculture and aquaculture, which had been linked to the global rise of AMR. By 2050, it is estimated that AMR will result in 10 million deaths per year and contribute to a shocking economic cost of 100 trillion USD, if we do not take action to tackle this devastating crisis [4]. In animals, the use of antimicrobials includes treatment and control of clinical bacterial infections as well as disease prevention and growth promotion. Although the evidence and mechanism of such benefits have not been clearly demonstrated, the apparent growth promotion

benefits of antimicrobials when using antimicrobials in animals have resulted in higher usage of antimicrobials in animals, even in the absence of disease. The danger of using antimicrobials in animals to humans was uncertain until 1997 when experts concluded that the usage of antimicrobials in food-producing animals causes AMR selection, in a consultation on "medical impact of the use of antimicrobials in food animals" organized by WHO in Berlin, Germany [5]. Since then, various studies have further supported the theory in which AMR selection and dissemination from animals can be attributed to uncontrolled antimicrobial usage in animals [6–10]. An example in dairy cattle production shows dairies from the conventional production have a higher prevalence of AMR enteric bacteria than dairies from the organic production as more antimicrobials are usually being used in the conventional practice [9].

In general, AMR is the capability of a microorganism to resist the inhibitory activity of an antimicrobial at a normal susceptibility level. AMR occurs in previously susceptible strain due to a prolonged adaptation of the microorganism on the antimicrobial, which results in the evolution of the particular stain to survive in such condition. This can be acquired via mutation of the gene or horizontal gene transfer from another microorganism, which includes conjugation, transformation and transduction. The subsequent AMR selection in bacteria in animals can then be disseminated to humans because of the food chain relationships [10]. Moreover, this cross-species transmission can also occur via direct contact between humans and animals or shared environmental sources that are contaminated. In dairy cattle production, the dairy products can also be contaminated with AMR strains in several ways like directly from the environment such as soil, water and fecal material or cross-contamination during food processing [9]. This ultimately causes public health concern regarding the consequences of antimicrobial use in animals on food safety issue.

In 2005, WHO's committee had set up a few criteria to classify medically important antimicrobials in human medicine [11]. Among the classifications, the criteria for critically important antimicrobials were used to establish the WHO List of Critically Important Antimicrobials for Human Medicine, also known as the WHO CIA List. A guideline based on the WHO CIA List was formed to minimize the adverse consequences of unrestrictive usage of medically important antimicrobials in human medicine, and since then it has been updated regularly, with the latest fifth edition being published in 2017. To combat the increasingly significant health threat posed by AMR, the 68th World Health Assembly adopted a global action plan in May 2015 that proposed interventions to tackle AMR and also emphasized on the "One Health" approach in addressing AMR.

In order to address this important health risks at the animal-human-ecosystem interfaces, a complementary partnership between the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE) and WHO was made to prevent, detect, control, eliminate and manage disease risks to human transferred directly or indirectly from domestic and wild animals [12]. Part of the OIE strategy on AMR and to support prudent use of antimicrobials includes four main objectives, namely, improving awareness and understanding, strengthening knowledge through surveillance and research, supporting good governance and capacity building and encouraging implementation of international standards [13]. Realizing the importance and its impact of this global issue in human and animal population, Malaysia is extremely committed with the cross-sectoral action plan and thus has drafted the Malaysian Action Plan on AMR (MyAP-AMR) to support the global action plan in 2017 under collaboration between Ministry of Health and Ministry of Agriculture and Agro-Based Industry, Malaysia [14].
