Antimicrobial Resistance: Navigating An Unfolding Public Health Crisis

Mahendra Pal^1, , Motuma Regassa², Tesfaye Rabuma³, Ravindra Zende⁴, Dhwani Upadhyay⁵ and Nidhi Panicker⁴

¹Narayan Consultancy on Veterinary Public Health and Microbiology, Bharuch, India

²Toke Kutaye Agricultural office, Ambo, Ethiopia

³School of Veterinary Medicine, Ambo University, Ambo, Ethiopia

⁴Department of Veterinary Public Health, College of Veterinary Science, Parel, Mumbai, India

⁵Department of Life Sciences, School of Sciences, GSFC University, Vadodara, Gujarat, India

Cite this paper:
Mahendra Pal, Motuma Regassa, Tesfaye Rabuma, Ravindra Zende, Dhwani Upadhyay and Nidhi Panicker. Antimicrobial Resistance: Navigating An Unfolding Public Health Crisis. American Journal of Medical and Biological Research. 2024; 12(1):27-35. doi: 10.12691/ajmbr-12-1-3

Abstract

Antimicrobial resistance (AMR) has public health and economic implications and has emerged as one of the leading public health threats in the world. It is estimated that bacterial antimicrobial resistance caused around 1.27 million human deaths globally in 2019. The overuse and misuse of antimicrobials in humans, animals, and plants are primarily responsible for the development of drug-resistant pathogens. AMR affects different countries regardless of income levels. The drivers and consequences of AMR are aggravated by poverty and inequality, affecting low- and middle-income countries the most. Antimicrobial resistance can occur when the parent compounds, their metabolites, and associated impurities of veterinary drugs in present in any edible portion of an animal product. It can result in severe consequences for humans if the concentration level consumed is higher than the standard residue limits. Residues of veterinary medicines are defined as pharmacologically active substances, principles, or degradation products and their metabolites that remain in animal-origin food obtained from animals that have been administered medicine. This review indicates the occurrence and public health impacts of antimicrobial and drug resistance. The most frequent reasons why antibiotic residues might be found in animal-derived food are overuse of antibiotics, negligence in observing withdrawal periods, and incorrect dosage forms. If antibiotics are used as "insurance" against disease-related livestock losses, misuse of antibiotics and the presence of antibiotic residues in food products can be difficult to control. These kinds of situations are common in many poor countries, where the need for antibiotics rises due to the incidence of infectious diseases. Products made from animals that have these residues in them may cause hypersensitivity reactions, bone marrow depression, cancer, mutagenicity, teratogenicity, and disturbance of normal gut flora. They may also cause increased resistance to antibiotic treatments. Therefore, adherence to strict withdrawal timings and guidelines is necessary to guarantee that animal products are safe for human consumption.

Keywords:
Antibiotics Antimicrobials Antimicrobial resistance Food chain Public health

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Cox, G., & Wright, G. D. Intrinsic antibiotic resistance: Mechanisms, origins, challenges, and solutions. International Journal of Medical Microbiology, 303, 287–292. 2013.
[2]	Olivares, J., Bernardini, A., Garcia-Leon, G. E., Corona, F., Sanchez, M. B., & Martínez, J. The intrinsic resistome of bacterial pathogens. Frontiers in Microbiology, 4, 103. 2013.
[3]	Smith, G. W., Gehering, R., & Riviere, J. E. Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows. Journal of the American Veterinary Medical Association, 224, 1827-1830. 2004.
[4]	Van Boeckel, T. P., Brower, C., Gilbert, M., Grenfell, B. T., Levin, S. A., Robinson, T. P., Teillant, A., & Laxminarayan, R. Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences of the United States of America, 112, 5649–5654. 2015.
[5]	Kolár, M., Urbánek, K., & Látal, T. Antibiotic selective pressure and development of bacterial resistance. International Journal of Antimicrobial Agents, 17, 357–363. 2001.
[6]	Millner, P. D. Manure management. In The Produce Contamination Problem; Elsevier: Amsterdam, The Netherlands; pp. 79–104. 2009.
[7]	Marshall, B. M., & Levy, S. B. Food animals and antimicrobials: Impacts on human health. Clinical Microbiology Reviews, 24, 718–733. 2011.
[8]	Moreno, L., & Lanusse, C. Veterinary drug residues in meat-related edible tissues. In New Aspects of Meat Quality; Woodhead Publishing Limited: United Kingdom; pp. 581–603. 2017.
[9]	Landoni, M. F., & Albarellos, G. The use of antimicrobial agents in broiler chickens. The Veterinary Journal, 205, 21–27. 2015.
[10]	Phu, V. D., Wertheim, H. F. L., Larsson, M., Nadjm, B., Dinh, Q.-D., Nilsson, L. E., Rydell, U., Le, T. T. D., Trinh, S. H., & Pham, H. M. Burden of hospital-acquired infections and antimicrobial use in Vietnamese adult intensive care units. PLoS One, 11, e0147544. 2016.
[11]	Spanu, V., Spanu, C., Virdis, S., Cossu, F., Scarano, C., & De Santis, E. P. L. Virulence factors and genetic variability of Staphylococcus aureus strains isolated from raw sheep’s milk cheese. International Journal of Food Microbiology, 153, 53–57. 2012.
[12]	Normanno, G., La Salandra, G., Dambrosio, A., Quaglia, N. C., Corrente, M., Parisi, A., Santagada, G., Firinu, A., Crisetti, E., & Celano, G. V. Occurrence, characterization, and antimicrobial resistance of enterotoxigenic Staphylococcus aureus isolated from meat and dairy products. International Journal of Food Microbiology, 115, 290–296. 2007.
[13]	Kashef, N., Djavid, G. E., & Shahbazi, S. Antimicrobial susceptibility patterns of community-acquired uropathogens in Tehran, Iran. Journal of Infection in Developing Countries, 4, 202–206. 2010.
[14]	Pal, M., Regessa, T., Rebuma, T., & Zende, R. Salmonellosis remains the hidden threat in our global food supply. American Journal of Medical and Biological Research, 12(1), 1–12. 2024.
[15]	Pal, M., Reubma, T., Regessa, T., & Zende, R. Methicillin-resistant Staphylococcus aureus (MRSA) remains a major threat to public health. American Journal of Public Health Research, 12(3), 48–53. 2024.
[16]	Hailu, D., Gelaw, A., Molla, W., Garedew, L., Cole, L., & Johnson, R. Prevalence and antibiotic resistance patterns of Salmonella isolates from lactating cows and in-contact humans in dairy farms, Northwest Ethiopia. Journal of Environmental and Occupational Science, 4, 171. 2015.
[17]	Mulchandani, R., Wang, Y., Gilbert, M., & Van Boeckel, T. P. Global trends in antimicrobial use in food-producing animals: 2020 to 2030. PLOS Global Public Health, 3(2), e0001305. 2023.
[18]	WHO. World Health Organization (2000) WHO global principles for the containment of antimicrobial resistance in animals intended for food. WHO/CDS/CSR/ APH/2000.4. www.who.int/ emc/diseases/ zoo/who_global_principles.html. Accessed on 25th October, 2024.
[19]	Chain, E., Florey, H. W., Gardner, A. D., Heatley, N. G., Jennings, M. A., Orr-Ewing, J., & Sanders, A. G. Penicillin as a chemotherapeutic agent. The Lancet, 236, 226–228. 1940.
[20]	Benveniste, R., & Davies, J. Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proceedings of the National Academy of Sciences, 70, 2276–2280. 1973
[21]	Wellington, E. M. H., Boxall, A. B. A., Cross, P., Feil, E. J., Gaze, W. H., Hawkey, P. M., Johnson-Rollings, A. S., Jones, D. L., Lee, N. M., & Otten, W. The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. The Lancet Infectious Diseases, 13, 155–165. 2013.
[22]	Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S., & Ciofu, O. Antibiotic resistance of bacterial biofilms. International Journal of Antimicrobial Agents, 35, 322–332. 2010.
[23]	Martínez, J. L., & Baquero, F. Emergence and spread of antibiotic resistance: Setting a parameter space. Upsala Journal of Medical Sciences, 119, 68–77. 2014.
[24]	WHO.Antimicrobial resistance: Global report on surveillance. World Health Organization: Geneva, Switzerland. 2014. https:// www.who.int/ publications/i/item/9789241564748, Accessed on 1st November, 2024.
[25]	Lambert, T. Antibiotics that affect the ribosome. Revue Scientifique et Technique, 31, 57. 2012.
[26]	You, Y., & Silbergeld, E. K. Learning from agriculture: Understanding low-dose antimicrobials as drivers of resistome expansion. Frontiers in Microbiology, 5, 284. 2014.
[27]	Nonaka, L., Ikeno, K., & Suzuki, S. Distribution of tetracycline resistance gene, tet(M), in gram-positive and gram-negative bacteria isolated from sediment and seawater at a coastal aquaculture site in Japan. Microbes and Environment, 22, 355–364. 2007.
[28]	Andersson, D. I., & Hughes, D. Microbiological effects of sublethal levels of antibiotics. Nature Reviews Microbiology, 12, 465. 2014.
[29]	Zwald, A. G., Ruegg, P. L., Kaneene, J. B., Warnick, L. D., Wells, S. J., Fossler, C., & Halbert, L. W. Management practices and reported antimicrobial usage on conventional and organic dairy farms. Journal of Dairy Science, 87, 191–201. 2004.
[30]	Kalman, M., Szöllősi, E., Czermann, B., Zimanyi, M., Szekeres, S., & Kalman, M. Milk-borne Campylobacter infection in Hungary. Journal of Food Protection, 63, 1426–1429. 2000.
[31]	Kurwijila, L. R., Omore, A., & Staal, S. Dairy sub-sector development strategy, East Africa regional initiatives in value chains. Lessons from ongoing R & D initiatives in dairy value chains, Rural Livelihood Development Company. Version Board 17 April 2009.
[32]	Milić, N., Milanović, M., Letić, N. G., Sekulić, M. T., Radonić, J., Mihajlović, I., & Miloradov, M. V. Occurrence of antibiotics as emerging contaminant substances in aquatic environment. International Journal of Environmental Health Research, 23, 296–310. 2013.
[33]	Mitchell, S. M., Ullman, J. L., Teel, A. L., Watts, R. J., & Frear, C. The effects of the antibiotic ampicillin, florfenicol, sulfamethazine, and tylosin on biogas production and their degradation efficiency during anaerobic digestion. Bioresource Technology, 149, 244–252. 2013.
[34]	Dubey, R. C., & Maheshwari, D. K. Practical Microbiology, 1st ed.; S. Chand Co. Ltd.: New Delhi, India. 2005.
[35]	Džidić, S., Šušković, J., & Kos, B. Antibiotic resistance mechanisms in bacteria: Biochemical and genetic aspects. Food Technology and Biotechnology, 46. 2008.
[36]	Yoneyama, H., & Katsumata, R. Antibiotic resistance in bacteria and its future for novel antibiotic development. Bioscience, Biotechnology, and Biochemistry, 70, 1060–1075. 2006.
[37]	Wooldridge, M. Evidence for the circulation of antimicrobial-resistant strains and genes in nature and especially between humans and animals. Revue Scientifique et Technique, 31, 231–247. 2012.
[38]	Marti, R., Scott, A., Tien, Y.-C., Murray, R., Sabourin, L., Zhang, Y., & Topp, E. Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest. Applied and Environmental Microbiology, 79, 5701–5709. 2013.
[39]	Fernando, P. R., & Birce, M. T. Review on multi-drug-resistant pathogens in foods of animal origin. Faculty of Veterinary, Agri-Food Campus of International Excellence (ceiA3), University of Córdoba, Córdoba, Spain, and Agriculture, Ankara University, Ankara, Turkey. Microbiology, 10, 3. 2019.
[40]	Cogliani, C., Goossens, H., & Greko, C. Restricting antimicrobial use in food animals: Lessons from Europe. Microbe, 6, 274. 2011.
[41]	Chang, Q., Wang, W., Regev‐Yochay, G., Lipsitch, M., & Hanage, W. P. Antibiotics in agriculture and the risk to human health: How worried should we be? Evolutionary Applications, 8, 240–247. 2015.
[42]	Landecker, H. Antibiotic resistance and the biology of history. Body & Society, 22, 19–52. 2016.
[43]	Schjørring, S., & Krogfelt, K. A. Assessment of bacterial antibiotic resistance transfer in the gut. International Journal of Microbiology, 2011.
[44]	Rehman, K., Kamran, S. H., & Akash, M. S. H. Toxicity of antibiotics. Antibiotics and Antimicrobial Resistance Genes in the Environment (pp. 234–252). Elsevier. 2020.
[45]	Baynes, R. D., Dedonder, K., Kisell, L., Mzyk, L., Marmulak, T., & Smith, G. Health concerns and management of select veterinary drug residues. Food and Chemical Toxicology, 88, 112–122. 2016.
[46]	Thong, B. Y., & Tan, T. C. Epidemiology and risk factors for drug allergy. British Journal of Clinical Pharmacology, 71(5), 684–700. 2011.
[47]	Woodhead, J. L., Yang, K., Oldach, D., MacLauchlin, C., Fernandes, P., Watkins, P. B., ... & Howell, B. A. Analyzing the mechanisms behind macrolide antibiotic-induced liver injury using quantitative systems toxicology modeling. Pharmaceutical Research, 36, 1–12. 2019.
[48]	Aiello, S. E., Lines, P. R., & Kehn, C. M. Anthelmintics. In The Merck Veterinary Manual, 9th ed.; Kenilworth, NJ, USA: Merck & Co., Inc.; pp. 2111–2124.
[49]	Bendesky, A., Menendez, D., & Ostrosky-Wegman, P. Is metronidazole carcinogenic? Mutation Research, 511(2), 133–144. 2002.
[50]	Cotter, P. D., Stanton, C., Ross, R. P., & Hill, C. The impact of antibiotics on the gut microbiota as revealed by high-throughput DNA sequencing. Discovery Medicine, 13, 193. 2012.
[51]	Foster, W., & Beecroft, M. Chemical exposures and human fertility. In Infertility Awareness Association of Canada. Available from: http://www.cwhn.ca/en. Accessed: 15 November 2024.
[52]	Ture, M., Fentie, T., & Regassa, B. Veterinary drug residue: The risk, public health significance, and its management. Veterinary Science Journal, 13, 555–856. 2019.
[53]	Horrigan, L., Robert, S. L., & Walker, P. How sustainable agriculture can address the environmental and human health arms of industrial agriculture. Environmental Health Perspectives, 110, 445–456. 2002.
[54]	Wilson, J. S., Otsuki, T., & Majumdar, B. Balancing food safety and risk: Do drug residue limits affect international trade in beef? Journal of International Trade and Economic Development, 12(4), 377–402. 2003.
[55]	Kaier, K., & Frank, U. Measuring the externality of antibacterial use from promoting antimicrobial resistance. Pharmacoeconomics, 28, 1123–1128. 2010.
[56]	Aarestrup, F. M., Seyfarth, A. M., Emborg, H.-D., Pedersen, K., Hendriksen, R. S., & Bager, F. Effect of abolishment of the use of antimicrobial agents for growth promotion on occurrence of antimicrobial resistance in fecal enterococci from food animals in Denmark. Antimicrobial Agents and Chemotherapy, 45, 2054–2059. 2001.
[57]	Addisalem, H. B., & Bayleyegn, M. Z. Tetracycline residue levels in slaughtered beef cattle from three slaughterhouses in Central Ethiopia. Journal of Global Veterinary Medicine, 8, 546–554. 2012.
[58]	Agmas, B., & Adugna, M. Antimicrobial residue occurrence and its public health risk of beef meat in Debre Tabor and Bahir Dar, Northwest Ethiopia. Veterinary World, 11(7), 902. 2018.
[59]	Manyi-Loh, C., Mamphweli, S., Meyer, E., & Okoh, A. Antibiotic use in agriculture and its consequential resistance in environmental sources: Potential public health implications. Molecules, 23(4), 795. 2018.
[60]	Smith, D. L., Dushoff, J., & Morris Jr, J. G. Agricultural antibodies and human health: Does antibiotic use in agriculture have a greater impact than hospital use? International Journal of Risk & Safety in Medicine, 17, 147–155. 2005.