Antimicrobial Resistance (AMR): Combative Measures and A Way Forward for one Health Approach

Antimicrobial Resistance (AMR): Combative Measures and A Way Forward for one Health Approach

Dr. Mohammad Iqbal Yatoo

Assistant Professor, FVSc and AH Shuhama

Principal Investigator of SERB, DST and BIRAC projects on infectious diseases of

livestock

iqbalyatoo@gmail.com

Abstract

Antimicrobials have saved billions of lives in both veterinary and medical sciences and ameliorated sufferings ever since their discovery and application against diverse microbial pathogens. However advent of antimicrobial resistance has become cause of concern. It is threatening whatever the achievements of antimicrobials have been over past so many decades including healthcare, socio-economy and sustainable development of world. Being one of the ten global public health threats it could make antimicrobials ineffective and useless and can kill more than 10 million people by 2050. It could cause loss of $1 trillion in the global economy and a surge of 1.2 trillion dollars in annual health expenditure by 2050 sinking the global GDP by 1.1–3.8%. Understanding basis and mechanisms of AMR is of utmost importance. Devising interventions that can support antimicrobials and can help in overcoming menace of AMR will be need of the future. The approaches should be judicious and limited use of antimicrobials in animals, regular screening for AMR, exploring novel targets and development of novel antimicrobials, alternatives to antimicrobials, monitoring and surveillance of AMR, awareness and outreach on AMR, and collaborations at national and international levels. One health initiatives need to be put in practice.

Key words: Antimicrobials, bacteria, microbes, one health, resistance

 Introduction

The World Health Organization (WHO) considers antimicrobial resistance “one of the ten global public health threats facing humanity” based on the predictions that, by 2050, it will be responsible for more than 10 million deaths per year, with a loss of more than 100 trillion dollars worldwide (Caneschi et al., 2023; WHO 2024). Considering the importance and need for combating AMR, quadripartite joint secretariat on antimicrobial resistance was constituted with global organisations including World Health Organisation (WHO), Food and Agriculture Organization of the United Nations (FAO), the UN Environment Programme (UNEP) and the World Organisation for Animal Health (WOAH) to drive multi-stakeholder engagement in AMR (WHO 2024).

AMR not only causes health related issues but also social and economic burdens, and poses challenges to achieving sustainable development goals (EC 2023).  Nearly 250000 people are dying annually in European Union and 700000 globally due to AMR. By 2050 AMR may cause more no. of deaths (10 million) which will be higher than cancer (EC 2023; WHO 2023). The cost of treatment is rising due to ineffectiveness of antimicrobial treatment by AMR. In the EU alone it is estimated that AMR costs EUR 1.5 billion annually in healthcare costs and productivity losses. As per estimates by 2050, AMR may pose economic crises similar to 2008 financial crisis. In the absence of intervention, the global economy could lose $1 trillion in total by 2050 (Al-Tawfiq et al., 2024). Because of AMR there will be a surge of 1.2 trillion USD in annual health expenditure by 2050 sinking the global GDP by 1.1–3.8%, (CDC, 2020). AMR threatens sustainable development goals of United Nations especially targets for good health and well-being (goal 3) (EC 2023).

AMR is a natural phenomenon and a selection mechanism of microbes to overcome adverse environment caused by antimicrobials (Mancuso et al., 2021; Arme et al., 2023). AMR has complex epidemiology (Caneschi et al., 2023). As underlined by Regulation (EU) 2019/6 (EU 2022), the AMR phenomenon in animals is much more complex than it is in humans and requires an even more attentive and conscious use of antibiotics (Caneschi et al., 2023).

Antimicrobial resistance is the ability of microorganisms to become increasingly resistant to antimicrobials to which they were susceptible (EC 2023).  It is the development of resistance in microorganisms against antimicrobials used for treating various microbial infections.  Natural selection and mutation helps microbial pathogens to develop this resistance which is transmitted from one generation to other. This selection process is exacerbated by humans through inappropriate use of antimicrobials, poor hygiene conditions and practices in healthcare settings or in the food chain facilitating the transmission of resistant microorganisms. This all results in less effectiveness of antimicrobials and ultimately uselessness (EC 2023).

The initial antimicrobial resistance is believed to be through random gene transfer events by bacteriophage-driven transduction (Magiorakos et al., 2012). Development of resistance against antimicrobial drugs due to selection of resistant microbes was followed by horizontal transfer of genes among microbial species producing resistant phenotypes (CDC 2021). Despite discovery of novel antimicrobials, microbes kept developing resistance through different mechanisms. With the advent of new antimicrobials from 1950 to 1970 AMR could not be noticed on that large scale however continuous use of same antimicrobials and less or no discovery of newer antimicrobials for a long time led to crises of AMR. Microbes have developed resistance to multiple drugs (MDR) and even there is also Extended-Spectrum Drug Resistance (XDR) and Pandrug Resistance (PDR)(Basak et al., 2016).

Resistance has developed in microbial pathogens against various antimicrobials. The examples of antimicrobial resistance among important zoonotic pathogens is given in Table 1. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the notable pathogens having developed antimicrobial resistance (Santajit and Indrawattana 2016). Staphylococcus aureus and Neisseria gonorrhoeae are resistant to benzyl penicillin and ceftriaxone (Shaskolskiy et al., 2019; Kang et al., 2020). Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) and carbapenemase-producing Enterobacterales (CPE) are other resistant bacteria (Jean and Hsueh 2011; CDC 2024). Third-generation cephalosporin-resistant E. coli, penicillins and cephalosporins extensively drug-resistant (XDR) Mycobacterium tuberculosis, and multidrug-resistant Acinetobacter baumannii, Enterobacteriaceae, Neisseria gonorrhoeae, and Pseudomonas aeruginosa are other serious examples of multidrug resistant pathogens (Kumar et al., 2021).

HIV, herpes, hepatitis, influenza viruses and SARS-CoV-2 are some examples of viruses having developed resistance. HIV are resistant to nucleoside RT inhibitors, nonnucleoside RT inhibitors, protease inhibitors. Influenza viruses are resistant to adamantanes (amantadine and rimantadine), herpes simplex virus to acyclovir, penciclovir, foscarnet, and vidarabine (Strasfeld and Chou 2010; Kumar et al., 2020). Cytomegalovirus is resistant to ganciclovir and focarnet and varicella-zoster virus is resistant to acyclovir (Strasfeld and Chou 2010; Chou 2021). Plasmodium, Giardia, Leishmania, Trypanosoma, Cryptosporidium or helminths are some examples of resistant parasites (Picot et al., 2022). Resistance to metronidazole and albendazole is well documented (Argüello-García et al., 2020; Curico et al., 2022). Decreased efficacy of Nitazoxanide against Cryptosporidium, benzimidazoles against Haemonchus contortus, Praziquantel against Echinococcus, ivermectin resistant endo and ectoparasites are other examples of antiparasitic resistance (Capela et al., 2019; Fissiha and Kinde 2021; Picot et al., 2022).

Understanding basis and mechanisms of resistance is important for devising interventions and curtailing the menace of AMR. Devising technointerventions that could support antimicrobials and help in combating AMR are need of the hour and requirements for safeguarding future. This involves efforts at regional, national and global levels. The main approaches that should be under focus include judicious and limited use of antimicrobials in animals, regular screening of antimicrobials for AMR, discovery of novel antimicrobials, alternatives to antimicrobials, monitoring and surveillance of AMR, awareness and outreach on AMR, collaborations at national and international levels and imposing the initiatives of one health.

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