Ipsita Kar1, Paviter Kaur2, Pravas Ranjan Sahoo3, Sourav Das4
1: PhD scholar, Department. of Veterinary Microbiology, ICAR-IVRI, Bareilly, Uttar Pradesh, 243122.
2: Professor, Department. of Veterinary Microbiology, COVS, GADVASU, Ludhiana, Punjab, 141004.
3: Assistant Professor, Department. of Veterinary Biochemistry, C.V. Sc & A.H, OUAT, Bhubaneswar, Odisha, 751003. 4: Veterinary Assistant Surgeon, F&ARD Department, Govt. of Odisha, 751001.
Antimicrobials are natural or chemical substances, administered parenterally, orally or topically to kill or prevent microbial growth (Kirbis et al., 2007). Nearly 80% of food-producing animals and poultry receive antibiotics in their lifetime (Lee et al., 2001). According to the World Organization for Animal Health (WOAH) estimation, altogether 76 704 tonnes veterinary antimicrobials were used in 2018, exclusively for food-producing animals. Antibiotics, including tetracyclines, amphenicols aminoglycosides, lincosamides, quinolones, polypeptides, macrolides, sulfonamides and β-lactams have been used most frequently in the veterinary sector (Marshall and Levy, 2011). The livestock population plays a pivotal role in achieving the country’s nutrition demands and securing the livelihoods of farmers, however, the growing dependency on antimicrobials has become a major challenge, that remains unresolved. On a global scale, the average annual consumptions of antimicrobials are estimated to be 172mg/kg, 148 mg/kg and 45 mg/kg in pig, poultry and cattle respectively, further a rise of 67% of its consumption by 2030 (Van Boeckel et al., 2015). The WHO approximates that, by 2050, antimicrobial resistance may cause 10 million deaths annually. The uncontrolled antibiotic usage is leading to an alarming surge in antimicrobial resistance, which results in higher treatment costs and mortality rates. Antimicrobial usage among livestock contributes to the reduced bacterial sensitivity towards different antibiotics, as the commensal microbes present in these animals may acquire AMR genes, serving as putative reservoirs of resistance genes. With the rising demand for animal food products, there is an enhancement in antimicrobial’s use and its persistency throughout the food chain, leading to serious health risks. Hence, strict regulation on antimicrobial’s use in animal food products should be imposed. In this context, we aim to explore the current load of antimicrobials, used in animal husbandry and their impact, as well as alternative strategies to mitigate AMR challenges, fostering a sustainable earth.
Antimicrobial usages:
Antibiotics in agricultural and allied fields were first introduced in 1938 through the application of sulphonamides. In 1948, the First licensed antibiotic i.e., Merck’s sulfaquinoxaline was applied in poultry feed as a prophylaxis of coccidiosis (Kirchhelle et al., 2017). Antimicrobial growth promotors were first documented as being used in the mid-1950s. Moore and Stokstad stated the first application of antibiotic growth promotors (AGPs) viz. sulfasuxidine streptothricin and streptomycin in chicken and pigs. These antimicrobials increase growth rate by thinning the gut’s mucous membrane, improving gut absorption and motility for better assimilation, and creating a favourable environment for beneficial gut microbes by destroying harmful bacteria (Nisha, 2008). The World Health Organization (WHO) classifies fluoroquinolones, third- and fourth-generation cephalosporins, macrolides, polymyxin, and glycopeptide as “highest priority critically important” antibiotics, used for humans. The antibiotics like Penicillin, macrolides, and fluoroquinolones are among the most frequently used drugs in human medicine, whereas, in the veterinary sector, tetracyclines, penicillin, and sulphonamides are commonly prescribed. In developed countries, 50-80% of the total antibiotics are used in livestock production. (Cully, 2014). Van Boeckel and coworkers reported that China, Brazil, and the United States hold the highest rank in utilizing antimicrobials for livestock production. Antibiotic consumption in India represented 3% of global consumption, with an estimated increment of 82% of consumption by 2030. Furthermore, in other developing countries like Myanmar, Indonesia, Nigeria, Peru, and Vietnam antimicrobial’s use is anticipated to be enhanced by 205%,202%,163%, 160% and 157% respectively by 2030. (Van Boeckel et al., 2015). Another study stated that over 60% of livestock owners administer antibiotics without veterinarian’s prescription (Al Masud et al., 2020), resulting in the accumulation of its residues. Anika et al. (2019) reported that antibiotics have been administered prophylactically as intramammary infusion in dairy cows to prevent mastitis. However, 90% of antibiotics have been documented as being used in sub-therapeutic doses for disease prevention, which contributes to a hike in antimicrobial resistance. A report by the US Food and Drug Administration (FDA) suggested that approximately 70% of antimicrobials related to human medicine are sold for animal use. The world’s meat production contributes to 73% of global antibiotic intake, highlighting the potential role of animal products in AMR proliferation. Antibiotic consumption concerning the manufacture of animal products is predicted to enhance by 11.5% by 2030, further exaggerating AMR. A survey in China suggested that the remnants of veterinary drugs namely ciprofloxacin, enrofloxacin, chlortetracycline, and oxytetracycline were detected in livestock manures (Zhao et al., 2010). The use of antibiotic-contaminated animal excreta, in the aquaculture system is a major contributor to the increased antibiotic residue in water bodies and their inhabitants (Brunson et al., 1999). Ma et al. (2021), also noted different levels of antibiotic residues in the faeces of cattle, chicken and swine, which can potentially lead to environmental contamination.
Antibiotics Residues in Animal product:
Antimicrobial residues, notably accelerate antibiotic resistance in livestock, ultimately leading to a hazardous health issue. These residues accumulate in the food products of animal origin through direct or indirect contamination. Direct contamination occurs during processing, storage, and transportation, mostly through contaminated air or water. In contrast, indirect contamination occurs when animals are fed on antibiotic-treated food. Various methods including liquid chromatography coupled with mass spectrometry, capillary electrophoresis (Blasco et al., 2009) and immunoassays like ELISA, fluoroimmunoassay (FIA), and time-resolved fluoroimmunoassay (TRFIA) (Cháfer-Pericás et al., 2010) have been used for identification of antibiotic residues. In layers, liver and kidneys have been reported with the highest antibiotic remnants. Ciprofloxacin is the predominant antibiotic found in the kidney and liver of broiler chickens, followed by enrofloxacin. Tetracycline residues also have been documented in livestock animals. Additionally, Amoxicillin and tetracycline residues were spotted in eggs at 11% and 16%, respectively. However, in milk, the distribution of amoxicillin, tetracycline, and ciprofloxacin residues was reported to be 26%, 17.5%, and 12.5%, respectively. (Hassan et al., 2021).
Impact of antibiotic residues:
Excessive antibiotic residues result in potential adverse effects including hypersensitivity, teratogenicity, mutation, and toxicity in both humans and animals. Penicillin, aminoglycosides, and tetracycline have been associated with different allergic reactions. (Katz and Brady 2000), however, beta-lactam antibiotics contribute to allergic cases in humans ((Davies and Davies, 2010). Yates (2003) reported, that idiosyncratic reactions such as skin allergy, rashes, and phototoxic dermatitis can be caused by tetracycline. Aminoglycoside usage may contribute to ototoxicity and nephrotoxicity, while macrolides are responsible for hepatoxicity and hypersensitivity. The continuous use of erythromycin in early pregnancy has led to cardiac anomalies in infants (WHO JECFA, 2009). Furthermore, oncogenic effects have been documented with sulfamethazine, oxytetracycline, and furazolidone antibiotics (Bacanlı et al., 2019). The most potent hazard, related to antibiotic traces is the emergence of antimicrobial-resistant bacteria, that serve as carriers, spreading antibiotic-resistance genes among livestock, humans, and the environment. The antimicrobial resistance is mainly associated with antibiotic residues which enter to human food chain through animal-derived products when the required withdrawal period is not managed. The Vancomycin-resistant enterococci have been reported in humans and are linked to the use of avoparcin in livestock farming. Similarly, Vieira et al. (2011) observed significant similarities between antibiotic-resistant E. coli strains, recovered from humans and animals, suggesting the contribution of food-borne E. coli to developing antibiotic resistance in humans. Some of the most common antimicrobial-resistant strains including antimicrobial-resistant Salmonella, macrolide- or fluoroquinolone-resistant Campylobacter, glycopeptide- or streptogramin-resistant Enterococci, and multiple antimicrobial-resistant E. coli (Phillips et al., 2004), are often cause treatment failure
Strategies and managemental approaches for antimicrobial residue reduction:
The levels of antimicrobial residues must be minimised to curtail their toxic effects and burden of antimicrobial resistance. Legislative orders must be implemented in every country for judicious antibiotic usage in livestock animals, ensuring the reduction in its residual effects. As per FDA regulations, the drug should be non-carcinogenic and administered in limited doses without any harmful residue (Bacanlı and Başaran, 2009). The FDA has prohibited the unbalanced use of several antibiotics in dairy animals, such as chloramphenicol, furazolidone, nitrofurazone, sulfonamides, and fluoroquinolones. In EU countries, subtherapeutic doses of antibiotic usage are restricted. The drug clearance period should be managed to reduce the harmful effects of animal-derived products, meant for human consumption. Recently in October 2024, the Food Safety and Standards Authority of India (FSSAI) banned the use of antibiotic groups including glycopeptides, nitrofurans, and nitroimidazoles, and five antibiotics ─ carbadox, chloramphenicol, colistin, streptomycin (and its metabolite dihydrostreptomycin), and sulphamethoxazole in livestock animals, to improve the quality of production and curb antimicrobial resistance. Various methods like fat loss, water loss, cooking, protein denaturation, and altered pH have been utilized to change the structural chemistry, solubility and drug residue concentrations (Javadi, 2011). In addition, sterilization, pasteurization, and ultra-heat treatment (UHT) have shown their potential to reduce milk residue. UHT has been documented to decrease tetracycline and oxytetracycline levels by 30% and 40% respectively, whereas sterilization more effectively lowers tetracycline levels by 98% (Zorraquino et al., 2011). In eggs, frying and Boiling reduce tetracycline residues by 47% and 52% and enrofloxacin residues by 58% and 69% respectively. (Ezenduka et al., 2011). The use of resin , activated charcoal and UV irradiation can also inactivate antibiotics (Nisha, 2008). Furthermore, promoting the use of herbal alternatives to antibiotics and probiotics could be beneficial in decreasing the antimicrobial load in animals and humans.
Conclusion Despite, the adoption of several strategies for declining antibiotic residues and AMR, it remains a significant global health challenge. Thereby, further research should be carried out on the persistence of antibiotic residues and their potential impact on One health. Stringent regulation must be implemented on unrestricted antibiotic usage in agriculture and animal husbandry sectors to confront their toxic residual effects. Additionally, a rapid surveillance system is necessary to monitor the widespread distribution of AMR and to mitigate its hazardous outcomes.