Worldwide traceability of antibiotic residues from livestock in wastewater and soil: A systematic review

  Citation: Robles-Jimenez, L.E.; Aranda-Aguirre, E.; Castelan-Ortega, O.A.; Shettino-Bermudez, B.S.; Ortiz-Salinas, R.; Miranda, M.; Li, X.; Angeles-Hernandez, J.C.; Vargas-Bello-Pérez, E.; Gonzalez-Ronquillo, M. Worldwide Traceability of Antibiotic Residues from Livestock in Wastewater and Soil: A Systematic Review. Animals 2022,12, 60. https://doi.org/ 10.3390/ani12010060 Academic Editor: Anshan Shan Received: 4 November 2021 Accepted: 22 December 2021 Published: 28 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). animals Systematic Review Worldwide Traceability of Antibiotic Residues from Livestock in Wastewater and Soil: A Systematic Review Lizbeth E. Robles-Jimenez 1, Edgar Aranda-Aguirre 1, Octavio A. Castelan-Ortega 1, Beatriz S. Shettino-Bermudez 2, Rutilio Ortiz-Salinas 2, Marta Miranda 3, Xunde Li 4, Juan C. Angeles-Hernandez 5, Einar Vargas-Bello-Pérez 6,* and Manuel Gonzalez-Ronquillo 1,7,* 1 Departamento de Nutricion Animal, Facultad de Medicina Veterinaria y Zootecnia, Instituto Literario 100 Ote, Universidad Autonoma del Estado de Mexico, Toluca 50000, Mexico; lizr[email protected] (L.E.R.-J.); [email protected] (E.A.-A.); [email protected] (O.A.C.-O.) 2Laboratorio de Análisis Instrumental, Departamento de Producción Agrícola y Animal, Universidad Autónoma Metropolitana Xochimilco, Calz, Hueso 1100, Villa Quietud, Coyoacan 04960, Mexico; [email protected] (B.S.S.-B.); [email protected] (R.O.-S.) 3Departamento de Anatomia, Produccion Animal y Ciencias Clinicas Veterinarias, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain; [email protected] 4 Western Institute for Food Safety and Security, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA; [email protected] 5Instituto de Ciencias Agropecuarias, Universidad Autónoma del Estado de Hidalgo, Av. Universidad km 1, Tulancingo de Bravo 43600, Mexico; [email protected] 6Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, DK-1870 Frederiksberg C, Denmark 7Sciences Department, Faculty of Humanities, Social and Health Sciences, Universidad de Magallanes, Avenida Bulnes, Punta Arenas 01855, Chile *Correspondence: [email protected] (E.V.-B.-P.); mr[email protected] (M.G.-R.) Simple Summary: This work focuses on reviewing research works on antibiotic residues, evaluating antibiotics used in livestock production and their excretion in animal products and in environmental matrices such as water and soil worldwide, according to each of the variables used such as antibiotic family, name, concentration (% and mg/kg or ppm), country, and continent where the residue was found. The main antibiotics used worldwide and in animal production are sulfonamides, tetracyclines, quinolones, penicillin, and cephalosporins. Abstract: The use of antibiotics in animal production are widely used for disease treatment, health protection, and as growth promoters. Common antibiotics used in veterinary medicine are excreted and eliminated through the sewage system, contaminating water and soil with negative effects on agricultural activities. This systematic review focuses on the trend of research works on antibiotic residues, evaluating antibiotics used in livestock production and their excretion in animal products and in environmental matrices such as water and soil. Our database was composed of 165 articles, reporting the concentration of antibiotic residues found in the environment, livestock (cow, sheep, pig, horse, chicken, rabbit, goat), aquatic and terrestrial animal tissues, animal products (milk and eggs), wastewater, and soil. The documents were obtained from Asia, Africa, North America, South America, Europe, and Oceania. A descriptive analysis of antibiotic residues found worldwide was analyzed according to each of the variables used such as antibiotic family, name, concentration (% and mg/kg or ppm) , and country and continent where the residue was found. The descriptive analysis was carried out using the “describe” function of psych package and pirate plots were drawn. According to our study, the main antibiotics used worldwide in animal production are sulfonamides, tetracyclines, quinolones, penicillin, and cephalosporins. At present, despite the trends of increased regulations on the use of antibiotics worldwide, antibiotics are still utilized in food animal production, and are present in water and soil, then, there is still the misuse of antibiotics in many countries. We need to become aware that antibiotic contamination is a global problem, and we are challenged to reduce and improve their use. Animals 2022,12, 60. https://doi.org/10.3390/ani12010060 https://www.mdpi.com/journal/animals Animals 2022,12, 60 2 of 21 Keywords: antibiotic residues; livestock; wastewater; antimicrobial resistance; soil residues 1. Introduction The absorption of antibiotics in animals after administration is often poor and a significant proportion of 70–90% may be excreted unmetabolized [ 1 ], and these residues remain unchanged in the environment [ 2 , 3 ]. The use of antibiotics in animal production has been increasing and they are widely used for disease treatment, health protection [ 4 – 6 ], and as growth promoters [ 7 , 8 ]. However, the family and active ingredient of the antibiotic vary with animal species (i.e., oxytetracycline, chlortetracycline, and tylosin are used in pigs in weaning and finishing; beta-lactam and tetracyclines in dairy cows; florfenicol and spectinomycin in calves) and the facet of production in which it is used [ 9 , 10 ]. All antibiotics used in veterinary medicine [ 11 , 12 ] are excreted and disposed over the sewage system, and in some cases, to sewage treatment plants [ 13 ]. This situation has polluting effects on water and soil with negative effects on agricultural activities, for example, it has been mentioned that in the soil, antibiotic residues are responsible for anoxic denitrification since they affect bacterial communities responsible for this process [14]. Antibiotic residues in food of animal origin also pose health risks such as bacterial resistance, toxicity, hypersensitivity reactions, cancer, and teratogenicity [ 15 ]. In May 2015, the 68th World Health Assembly recognized the importance of antimicrobial resistance and adopted a plan to reduce the unnecessary use of antimicrobials in humans and animals [ 16 , 17 ]. Thus, since 2006, member countries of the European Union [ 18 ], and since 2011, New Zealand and the Republic of Korea have banned the use of antibiotics as growth promoters [ 19 ]. Other countries such as Australia, Canada, Japan, and the United States have applied policies and regulations to ensure that they are only used by licensed veterinarians [ 20 – 22 ]. Large meat producing countries such as Argentina, Brazil, China, India, Indonesia, the Philippines, Russia, and South Africa have not banned the use of antibiotics as growth promoters [ 23 ]. The greatest uncertainty about antibiotic use in livestock is found in low-income countries due to the lack of information on the use of antibiotics [ 16 ]. The differences that exist in the use of antibiotics both by species and by country due to the policies implemented worldwide make quantification very difficult (i.e., only 42 countries in the world have a system for collecting data on the use of antimicrobials in livestock) [ 24 ]. Antibiotic use is estimated to increase by 67% by 2030, with China, Brazil, India, South Africa, and Russia being the main consuming countries [ 25 ]. Therefore, this review focuses on the trend of research work on antibiotic residues found in environmental samples such as water, soil, and livestock products, aquatic and terrestrial animal tissues, and animal products (milk and eggs). 2. Materials and Methods 2.1. Search Strategy and Selection Criteria The information search focused on studies reporting veterinary antibiotic residues found in the environment, wastewater, soil, and their bioaccumulation in animal tissues and products worldwide. For this purpose, a database of publications specifying antibiotic residues worldwide was created and the articles used covered the years 2000 to 2019. The publications were obtained from different databases such as ScienceDirect 2021, Scopus, Di-alnet, SciELO, Science Research, PubMEd, Redalyc, and Google Scholar. The search string with the particular topic was supported by Boolean operators (“and”, “or”). All search terms within a string were checked for a “title, abstract, and keyword”. The keywords used were antibiotic residues in the environment (wastewater and soil), traceability, animal husbandry, animal species (cow, sheep, pig, horse, chicken, rabbit, goat), aquatic and terrestrial animal tissues, animal products (milk and eggs), bioaccumulation in animal tissues, and antibiotic concentrations (% and mg/kg). The search for information was carried out by continent. Animals 2022,12, 60 3 of 21 The Council Directive 96/23/EC, Annex 1 [ 26 ], classifies veterinary medicinal products and substances with anabolic effects used in animal feed into two groups: Group A and Group B. Group A contains substances that have anabolic effects such as stilbenes (diethylstilbestrol), steroids, androgens (trenbolone acetate), gestagens (melengestrol acetate), oestrogens (17-beta estradiol), resorcyclic acid lactones (zeranol), beta agonist (clenbuterol), and nitrofurans. Group B contains all veterinary medicinal products (e.g., sulfonamides, quinolones). The ranking order of antibiotic families based on their occurrence (%) is shown in Table 1[ 27 ]; antibiotics highlighted in bold letters represent their family and the most widely used antibiotics, respectively. 2.2. Data Extraction and Analysis Our database was composed of 165 articles (Figure 1) reporting the concentration of antibiotic residues found in the environment, livestock (cow, sheep, pig, horse, chicken, rabbit, goat), aquatic and terrestrial animal tissues, animal products (milk and eggs), wastewater, and soil (Supplementary Table S1). The study focused on assessing the presence of antibiotics in wastewater management systems, which are mainly used in semi-urban, rural, and remote areas as well as animal farms, where the installation of a centralized sewage system is not feasible, and many of these wastes seep through groundwater or simply remain in the soil, hence the importance of showing that antibiotic residues exist in water and soil. The documents were obtained from Asia, Africa, North America, South America, Europe, and Oceania (Table 2). A descriptive analysis of antibiotic residues found worldwide was analyzed according to each of the variables used such as antibiotic family, name, concentration (% and mg/kg or ppm), and country and continent where the residue was found. The descriptive analysis was carried out using the “describe” function of psych package [28] and pirate plots were drawn using the Yarrr package [29]. Figure 1. PRISMA study flow diagram of the systematic review from the initial search and screening to the final selection of publications to be included in the systematic review. Animals 2022,12, 60 4 of 21 Table 1. Categorization per family of veterinary antibiotics for food-producing animals, representing their occurrence (%). Antibiotics Penicillins 87.1% Tetracyclines 87.1% Aminoglycosides 77.1% Macrolides 77.1% Sulfonamides 70% Quinolones 68.6% Polypeptides 64.3% Cephalosporins 58.6% Phenicols 51.4% Lincosamides 51.4% Natural Penicillins Benzylpenicillin Penethamate hydroxide Penicillin procaine Amdinopenicillins Mecillinam Aminopenicillins Amoxicillin Ampicillin Hetacillin Aminopenicillin plus Betalactamase inhibitor Amoxicillin_Clavulanic Acid Carboxypenicillins Ticarcillin Tobicillin Ureido Penicillin Aspoxicillin Phenoxypenicillins Phenoxymethylpenicillin Phenethicillin Antistaphylococcal Penicillins Cloxacillin Dicloxacillin Nafcillin Oxacillin Chlortetracycline Doxycycline Oxytetracycline Tetracycline Aminocyclitol Spectinomycin Aminoglycosides Streptomycin Dihydrostreptomycin Framycetin Kanamycin Neomycin Paromomycin Apramycin Gentamicin Tobramycin Amikacin Azalide Tulathromycin Macrolides C14 Erythromycin Macrolides C16 Josamycin Kitasamycin Spiramycin Tilmicosin Tylosin Mirosamycin Terdecamycin Sulfachlorpyridazine Sulfadiazine Sulfadimerazin Sulfadimethoxine Sulfadimidine Sulfadoxine Sulfafurazole Sulfaguanidine Sulfamethazine Sulfadimethoxazole Sulfamethoxine Sulfamonomethoxine Sulfanilamide Sulfaquinoxaline Sulfonamides and Diaminopyrimidines Sulfamethoxypyridazine Trimethoprim+ Sulfonamide Diaminopyrimidines Baquiloprim Trimethoprim Quinolones 1G Flumequin Miloxacin Nalidixic acid Oxolinic acid Quinolones 2G (Fluoroquinolones) Ciprofloxacin Danofloxacin Difloxacin Enrofloxacin Marbofloxacin Norfloxacin Ofloxacin Orbifloxacin Enramycin Gramicidin Bacitracin Polypeptides cyclic Colistin Polymixin Cephalosporin 1G Cefacetrile Cefalexin Cefalotin Cefapyrin Cefazolin Cefalonium Cephalosporin 2G Cefuroxime Cephalosporin 3G Cefoperazone Ceftiofur Ceftriaxone Cephalosporin 4G Cefquinome Florphenicol Thiamphenicol Pirlimycin Lincomycin Pleuromutilins 48.6% Ionophores 42.9% Novobiocin 31.4% AnsamycinRifamycins 30% Fosfomycin 7.1% Streptogramins 5.7% Quinoxalines 4.3% Orthosomycins 4.3% Fusidic Acid 1.4% Bicyclomycin 1.4% Tiamulin Valnemulin Lasalocid Maduramycin Monensin Narasin Salinomycin Semduramicin Novobiocin Rifampicin Rifaximin Fosfomycin Virginiamycin Fusidic acid Lasalocid Maduramycin Monensin Narasin Salinomycin Semduramicin Fusidic acid Bicozamycin Adapted from OIE, List of antimicrobials of veterinary importance [27]. Animals 2022,12, 60 5 of 21 Table 2. Characteristics of the reviewed studies describing the number of articles found by continent and country to which they belong. Geographical Area n= 165 Data Source Animal/Environment n= 165 Data Source for Livestock n= 165 North America (a) 30 Livestock 112 Beef cattle 10 South America (b) 33 Soil 34 Dairy cattle 29 Europe (c) 31 Wastewater 19 Pork 23 Asia (d) 35 Chicken 19 Africa (e) 26 Egg 12 Oceania (f) 10 Milk 32 Sheep meat 15 Fish 13 Shrimp 12 (a) North America: Canada (n= 4), USA (n= 14), Mexico (n= 12). (b) South America: Peru (n= 6), Chile (n= 6) , Venezuela (n= 8), Colombia (n= 9), Brazil (n= 1), Ecuador (n= 2), Argentina (n= 2). (c) Europe: Denmark (n= 3) , Germany (n= 6), France (n= 3), the Netherlands (n= 2), Austria (n= 1), Spain (n= 7), UK (n= 3), Romania (n=4) , Italy (n= 1), Turkey (n= 1). (d) Asia: Vietnam (n= 5), China (n= 12), Israel (n= 1), Bangladesh (n= 4), Iraq (n= 5) , Turkey (n= 2), Pakistan (n= 2), Singapore (n= 1), Iran (n= 3), India (n= 2). (e) Africa: Ghana (n= 2), Algeria (n= 1) , Tanzania (n= 2), Egypt (n= 5), Sudan (n= 1), South Africa (n= 3), Nigeria (n= 5), Madagascar (n= 1) , Ethiopia (n= 1), Morocco (n= 1), Tunisia (n= 2), Kenya (n= 2). (f) Oceania: Australia (n= 7), New Zealand (n= 3). 3. Results 3.1. Veterinary Antibiotics as Pollutants in Different Continents From all antibiotics produced worldwide in 2015, two-thirds (65,000 tones) were used for animal husbandry. The highest consumption of antibiotics in livestock was in China (>15,000 tons), followed by the USA with 9000 tons, while France and Canada reported a consumption of approximately 2000 tons [30]. According to the antibiotic management situation, the WHO has tried to create an observational and ecological database to define which antimicrobials are medically important. Recommendations and web pages have been derived for consultation as defined by the Guideline Development Group (GDG) [31]. The residue levels of antibiotics based on continent showed a marked variability among antimicrobial families. The antimicrobial with the highest concentration in Asia was cephalosporins (450 ± 353.55 ppm), followed by fluroquinolone (129.44 ±509.81 ppm) . The tetracyclines were the antibiotic family with highest residual concentration in Africa (176.74 ±930.75 ppm) and North America (106.11 ± 146.86 ppm). In South America, the family of antibiotics that depicted the highest level of residues was fluroquinolones (726.91 ±1437.29 ppm) , followed by macrolides (407 ± 574.17 ppm). In Europe, the largest concentration of residues was shown by ß-lactam (509.2 ± 1220.29 ppm), followed by nitroimidazole (250 ppm). The studies developed in Oceania only reported antimicrobial resistance of aminoglycoside (8.41 ±15.74 ppm) and fluoroquinolones (1.9 ±2.68 ppm) (Figure 2). Figure 2. Cont. Animals 2022,12, 60 6 of 21 Figure 2. Cont. Animals 2022,12, 60 7 of 21 Figure 2. Antibiotics (ppm) used in Asia, Africa, North America, South America, Europe, and Oceania. ( a ) Antibiotics (ppm) used in Asia. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. ( b ) Antibiotics (ppm) used in Africa. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. ( c ) Antibiotics (ppm) used in North America. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. ( d ) Antibiotics (ppm) used in South America. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. ( e ) Antibiotics (ppm) used in Europe. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. ( f ) Antibiotics (ppm) used in Oceania. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. 3.2. Residues of Veterinary Antibiotics in Animal Products and Derivatives According to the main animal products reported in the analyzed studies, the largest concentration of residues was found in chicken (341.44 ± 1025.76 ppm), shrimp (259.02 ±691.38 ppm) , and cow’s milk (100.65 ± 318.41 ppm) (Figure 3). Studies that reported microbial residues of pork meat showed the largest concentration in nitroimidazole (15 ppm), tetracyclines (10.25 ±17.23) , and aminoglycoside (4.54 ± 6.15 ppm). Aminoglycosides were the antimicrobials that had the highest levels of residues in beef meat (2.1 ± 2.34 ppm). In cow’s milk, the cephalosporins and macrolides were the families of antibiotics that showed the highest levels of residues. However, these antibiotic families had a reduced number of reports. On the other hand, there were several studies that reported residues of tetracyclines in cow’s Animals 2022,12, 60 8 of 21 milk with a high variability (132.36 ± 480.19 ppm). For example, a study [ 32 ] reported concentrations of tetracycline residues as high as 1800 ppm (Figure 4). Studies [ 33 , 34 ] that have reported residues of antimicrobial in sheep meat only referred to concentrations of fluoroquinolones (0.73 ±0.69 ppm), tetracyclines (0.5 ±0.54 ppm), and ß-lactam (0.04 ±0.04 ppm). Figure 3. Presence of antibiotics in animal products. Points represent the raw data; bar/line is the descriptive statistic (mean); bean is the smoothed density curve showing the full data distribution; and brackets represent the confidence intervals. Figure 4. Cont. Animals 2022,12, 60 9 of 21 Figure 4. Cont. Animals 2022,12, 60 16 of 21 ganisms such as Salmonella spp, Campylobacter spp,Enterococcus faecalis, and others [ 77 ]. Therefore, records on the effects of antibiotics in veterinary use is needed for the development of national and international policies related to the issue of microbial resistance. 4.3. Impact of Antibiotic Residues in Water and Soil With the aforementioned background such as the inappropriate use of antibiotics in animal production, antibiotic residues are excreted in feces or urine and present in environmental matrices such as soil, water, and vegetation, which may cause risks to human health [ 78 ], hence the latest trends in antimicrobial resistance. For example, in the United States (U.S.), 70% of antibiotics were used in animal production, which is eight times the amount used in human medicine [ 79 ]; in 2013, U.S. livestock producers purchased 14,900 tons of antimicrobials [ 80 ], which represents a large amount of antibiotics potentially disposed of into the environment (aquatic waste and soil). Van Boeckel et al. [ 25 ] estimated that between 2010 and 2030, the use of antibiotics in food animal production will increase by 67%, from 63,151 ±1560 tons to 105,596 ±3605 tons, which could increase the issue of antimicrobial resistance in future generations. Many of the antibiotics and hormones administered to animals cannot be fully absorbed or metabolized in the body and are excreted directly into the wastewater system [81–83] . Consequently, wastewater systems are an important pathway for the removal and distribution of antibiotics [ 84 ]. Many antibiotics present in wastewater are removed and transported to sewage sludge during sewage treatment [ 85 ], indicating that sludge can serve as an important reservoir for antibiotics (Figure 6). Furthermore, it has been recognized that sludge disposal such as agricultural application and landfilling can potentially release antibiotics into the environment and may pose potential risks to animal and human health ecosystems [86,87]. Triclosan, sulfonamides, and trimethoprim are the most frequently found antibiotics in soil [ 71 ], however, the highest concentrations found were in fluoroquinolones (32.34 ±97.52) (Figure 6). Quinolones, sulfonamides, and trimethoprim have been the most frequently found antibiotics in water, which exceed 1 µ g/L in environmental samples [ 88 ] (Figure 5; fluoroquinolones 325.0 ± 471.69 ppm). The persistence of these antibiotics in the environment may be due to their degradation time, since some antibiotics such as penicillin degrade easily within hours or a few days, while other antibiotics such as macrolides (i.e., tylosin) , fluoroquinolones, and tetracyclines can persist for several months or even years (Figure 6, Soil) [89]. It has been shown through molecular markers that the main cause of antibiotic residues in the environment is due to livestock feces as doses much higher than those prescribed are applied to the human population, as demonstrated in animal excrement in the United States, where values exceeded 100 times more than those found in wastewater of anthropogenic origin [90]. It is important to control the doses used in livestock production to avoid pathogen resistance to antibiotics and water contamination as wastewater in some areas is used as an alternative for the irrigation of agricultural fields [45,46]. Animal production systems have separate drains from the municipal ones, and in many cases, the waste is concentrated in waste lagoons where antibiotics accumulate. In these lagoons, sludge or water is obtained and applied to nearby land, so there is close contact with soil microbiota, or in rainy seasons, there is runoff or filtration of these compounds that reach aquatic bodies or groundwater [ 91 ]. Therefore, there is environmental pressure on microorganisms in soil and water when antibiotic contamination is present in the environment, forcing a selection on the reduction in the diversity and composition of the microbial community. Appreciating that antibiotic exposure tends to favor an increase in Gram-negative bacteria compared to Gram-positive bacteria, this will result in the disruption or loss of bacteria that play key ecological roles such as in the decomposition of matter [92,93]. Animals 2022,12, 60 17 of 21 5. Conclusions In recent years, it has been demonstrated that antibiotic residues are present worldwide in wastewater, soil, and animal production, the most common being sulfonamides, tetracyclines, quinolones, penicillins, and cephalosporins. New international policies have limited their use as therapeutics, restricting their use as growth promoters in animal production. Intensive livestock production must change, as it would be impossible to sustain current market demands without the use of antimicrobials or friendlier alternatives, with a future decrease in antimicrobial resistance, so we are challenged to reduce their use. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/ani12010060/s1, Table S1: Number of studies reporting use of antibiotics per family and active ingredient, by livestock production, soil, and wastewater. Author Contributions: Conceptualization, L.E.R.-J., E.A.-A., E.V.-B.-P., and M.G.-R.; Methodology, L.E.R.-J., M.G.-R., and E.V.-B.-P.; Software, L.E.R.-J. and E.A.-A.; Validation, B.S.S.-B., R.O-S., M.M., and L.E.R.-J.; Formal analysis, E.A.-A., L.E.R.-J., and M.G.-R.; Investigation, L.E.R.-J., E.A.-A., and M.G.-R.; Resources, M.G.-R. and O.A.C.-O.; Data curation, L.E.R.-J., E.A.-A., and M.G.-R., Writing— original draft preparation, O.A.C.-O., B.S.S.-B., R.O.-S., E.A.-A., and L.E.R.-J.; Writing—review and editing, L.E.R.-J., M.M., X.L., E.V.-B.-P., J.C.A.-H., and M.G.-R.; Visualization and editing, L.E.R.-J., M.M., X.L., E.V.-B.-P., J.C.A.-H., and M.G.-R.; supervision, L.E.R.-J., E.V.-B.-P., and M.G.-R.; Project administration, O.A.C.-O. and M.G.-R.; Funding acquisition, O.A.C.-O. and M.G.-R. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by Universidad Autonoma del Estado de Mexico, 4335/2017. Institutional Review Board Statement: Not applicable. Data Availability Statement: Upon request to the corresponding author. Acknowledgments: L.E. Robles was granted the CONACyT Fellowship for her doctoral studies at the “Programa de Doctorado en Ciencias Agropecuarias y Recursos Naturales” UAEMex. Conflicts of Interest: The authors declare no conflict of interest. References 1. Kumar, K.; Gupta, S.C.; Baidoo, S.K.; Chander, Y.; Rosen, C.J. Antibiotic uptake by plants from soil fertilized with animal manure. J. Environ. Qual. 2005,34, 2082–2085. [CrossRef] [PubMed] 2. Liu, J.; Zhao, Z.; Orfe, L.; Subbiah, M.; Call, D.R. Soil-borne reservoirs of antibiotic-resistant bacteria are established following therapeutic treatment of dairy calves. Environ. Microbiol. 2016,18, 557–564. [CrossRef] 3. Tasho, R.P.; Cho, J.Y. Veterinary antibiotics in animal waste, its distribution in soil and uptake by plants: A review. Sci. Total Environ. 2016,563–564, 366–376. [CrossRef] 4. 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