Abstract

Antibiotics have traditionally been used to prevent and treat common diseases in farm animals. However, residual antibiotics in dairy products and meat remain a serious public health problem, which is associated with antibiotic resistance. The research objective was to assess the impact of antibiotic contamination on the quality and safety of dairy products, the microbiological composition of milk, and antibiotic-resistant bacteria.
The study featured six years of Russian and foreign scientific articles registered in PubMed (National Center for Biotechnology Information, USA), Scopus and ScienceDirect (Elsevier, the Netherlands), Web of Science (Clarivate, USA), and eLibrary.ru.
The analysis involved 63 foreign and domestic sources. Residual antibiotics in milk inhibits the vital activity of lactic acid bacteria, which, in its turn, disrupts the technological process of yogurts, cheeses, etc. After such processing as normalization, pasteurization, and homogenization, antibiotics accumulate in fermented dairy products and bind with milk proteins and fats. Antibiotics, in their initial amount, enter yoghurts from dairy raw materials. In cheese production, antibiotics usually pass into the whey, but aminoglycosides, quinolones, and tetracyclines remain in the finished product because they bind with the protein fraction.
The problem of biological safety of dairy products is associated with antibiotic resistance developed by human intestinal microbiota. This problem remains understudied, and the number of scientific papers on the matter is limited.

Keywords

Antibiotics, milk, livestock products, antibiotic resistance, biosafety, dairy products, lactic acid bacteria

Contribution

All the authors contributed equally to the study and bear equal responsibility for information published in this article.

CONFLICTS OF INTEREST

The authors declare that there is no conflict of interests regarding the publication of this article.

REFERENCES

1. Treiber FM, Beranek-Knauer H. Antimicrobial residues in food from animal origin – A review of the literature focusing on products collected in stores and markets worldwide. Antibiotics. 2021;10(5). https://doi.org/10.3390/antibiotics10050534
2. Kharitonov DV, Kharitonova IV, Prosekov AYu. The concept of synbiotics and synbiotic dairy products development. Food Processing: Techniques and Technology. 2013;31(4):91–94. (In Russ.).
3. Barrett JR, Innes GK, Johnson KA, Lhermie G, Ivanek R, Greiner Safi A, et al. Consumer perceptions of antimicrobial use in animal husbandry: A scoping review. PLoS One. 2021;16(12). https://doi.org/10.1371/journal.pone.0261010
4. Chaplygina OS, Prosekov AYu, Vesnina AD. Determining the residual amount of amphenicol antibiotics in milk and dairy products. Food Processing: Techniques and Technology. 2022;52(1):79–88. (In Russ.). https://doi.org/10.21603/2074-9414-2022-1-79-88
5. Prosekov AYu, Ostroumov LA. Innovation management biotechnology of starter cultures. Food Processing: Techniques and Technology. 2016;43(4):64–69. (In Russ.).
6. Faustini M, Quintavalle Pastorino G, Colombani C, Chiesa LM, Panseri S, Vigo D, et al. Volatilome in milk for Grana Padano and Parmigiano Reggiano cheeses: A first survey. Veterinary Sciences. 2019;6(2). https://doi.org/10.3390/vetsci6020041
7. László N, Lányi K, Laczay P. LC-MS study of the heat degradation of veterinary antibiotics in raw milk after boiling. Food Chemistry. 2018;267:178–186. https://doi.org/10.1016/j.foodchem.2017.11.041
8. El-Sayed A, Kamel M. Bovine mastitis prevention and control in the post-antibiotic era. Tropical Animal Health and Production. 2021;53(2). https://doi.org/10.1007/s11250-021-02680-9
9. Landers TF, Cohen B, Wittum TE, Larson EL. A review of antibiotic use in food animals: Perspective, policy, and potential. Public Health Reports. 2020;127(1):4–22. https://doi.org/10.1177/003335491212700103
10. de Albuquerque Fernandes SA, Magnavita APA, Ferrao SPB, Gualberto SA, Faleiro AS, Figueiredo AJ, et al. Daily ingestion of tetracycline residue present in pasteurized milk: A public health. Environmental Science and Pollution Research. 2019;21(5):3427–3434. https://doi.org/10.1007/s11356-013-2286-5
11. Výrostková J, Regecová I, Dudriková E, Marcinčák S, Vargová M, Kováčová M, et al. Antimicrobial resistance of Enterococcus sp. isolated from sheep and goat cheeses. Foods. 2021;10(8). https://doi.org/10.3390/foods10081844
12. Quintanilla MP, Beltrán C, Peris B, Rodríguez MM, Molina P. Antibiotic residues in milk and cheeses after the off-label use of macrolides in dairy goats. Small Ruminant Research. 2018;167:55–60. https://doi.org/10.1016/j.smallrumres.2018.08.008
13. Gaudin V. Advances in biosensor development for the screening of antibiotic residues in food products of animal origin – A comprehensive review. Biosensors and Bioelectronics. 2017;90:363–377. https://doi.org/10.1016/j.bios.2016.12.005
14. Jank L, Martins MT, Arsand JB, Campos Motta TM, Hoff RB, Barreto F, et al. High-throughput method for macrolides and lincosamides antibiotics residues analysis in milk and muscle using a simple liquid-liquid extraction technique and liquid chromatography-electrospray-tandem mass spectrometry analysis (LC-MS/MS). Talanta. 2017;144:686–695. https://doi.org/10.1016/j.talanta.2015.06.078
15. Samreen, Ahmad I, Malak HA, Abulreesh HH. Environmental antimicrobial resistance and its drivers: A potential threat to public health. Journal of Global Antimicrobial Resistance. 2021;27:101–111. https://doi.org/10.1016/j.jgar.2021.08.001
16. Navrátilova P, Borkovcova I, Stastkova Z, Bednarova I, Vorlova L. Effect of cephalosporin antibiotics on the activity of yoghurt cultures. Foods. 2022;11(18). https://doi.org/10.3390/foods11182751
17. Ianni F, Pucciarini L, Carotti A, Saluti G, Moretti S, Ferrone V, et al. Hydrophilic interaction liquid chromatography of aminoglycoside antibiotics with a diol-type stationary phase. Analytica Chimica Acta. 2018;1044:174–180. https://doi.org/10.1016/j.aca.2018.08.008
18. Castrica M, Rebucci R, Giromini C, Tretola M, Cattaneo D, Baldi A. Total phenolic content and antioxidant capacity of agri-food waste and by-products. Italian Journal of Animal Science. 2018;18(1):336–341. https://doi.org/10.1080/1828051X.2018.1529544
19. Pazzola M, Stocco G, Dettori ML, Bittante G, Vacca GM. Effect of goat milk composition on cheesemaking traits and daily cheese production. Journal of Dairy Science. 2019;102(5):3947–3955. https://doi.org/10.3168/jds.2018-15397
20. Pogurschi E, Ciric A, Zugrav C, Patrascu D, Pogurschi E. Identification of antibiotic residues in raw milk samples coming from the metropolitan area of Bucharest. Agriculture and Agricultural Science Procedia. 2019;6:242–245. https://doi.org/10.1016/j.aaspro.2015.08.066
21. Zhang J, Wang J, Jin J, Li X, Zhang H, Shi X, et al. Prevalence, antibiotic resistance, and enterotoxin genes of Staphylococcus aureus isolated from milk and dairy products worldwide: A systematic review and meta-analysis. Food Research International. 2022;162. https://doi.org/10.1016/j.foodres.2022.111969
22. Wu Q, Zhu Q, Liu Y, Shabbir MAB, Sattar A, Peng D, et al. A microbiological inhibition method for the rapid, broad-spectrum, and high-throughput screening of 34 antibiotic residues in milk. Journal of Dairy Science. 2019;102(12):10825–10837. https://doi.org/10.3168/jds.2019-16480
23. de Paula ACL, Medeiros JD, de Azevedo AC, de Assis Chagas JM, da Silva VL, Diniz CG. Antibiotic resistance genetic markers and integrons in white soft cheese: Aspects of clinical resistome and potentiality of horizontal gene transfer. Genes. 2018;9(2). https://doi.org/10.3390/genes9020106
24. Beltrán MC, Morari-Pirlog A, Quintanilla P, Escriche I, Molina MP. Influence of enrofloxacin on the coagulation time and the quality parameters of goat’s milk yoghurt. International Journal of Dairy Technology. 2018;71(1):105–111. https://doi.org/10.1111/1471-0307.12388
25. Bagré TS, Samandoulougou S, Traore M, Illy D, Bsadjo-Tchamba G, Bawa-Ibrahim H, et al. Detection of antibiotics residues in dairy products sold in Ouagadougou, Burkina Faso. Journal of Applied Biosciences. 2019;87:8105–8112. https://doi.org/10.4314/jab.v87i1.11
26. Piñeiro SA, Cerniglia CE. Antimicrobial drug residues in animal-derived foods: Potential impact on the human intestinal microbiome. Journal of Veterinary Pharmacology and Therapeutics. 2020;44(2):215–222. https://doi.org/10.1111/jvp.12892
27. Eluk D, Ceruti R, Nagel O, Althaus R. Effect of thermal treatment of whey contaminated with antibiotics on the growth of Kluyveromyces marxianus. Journal of Dairy Research. 2019;86(1):102–107. https://doi.org/10.1017/S0022029919000098
28. Rodionov GV, Selitskaya OV, Kostomakhin NM, Olesyuk AP, Ageyeva AS. Effect of antibiotics on quality and safety of raw milk and milk products. Izvestiya of Timiryazev Agricultural Academy. 2019;(4):88–103. (In Russ.).
29. Giraldo J, Althaus RL, Beltrán MC, Molina MP. Antimicrobial activity in cheese whey as an indicator of antibiotic drug transfer from goat mil. International Dairy Journal. 2017;69:40–44. https://doi.org/10.1016/j.idairyj.2017.02.003
30. Ghimpețeanu OM, Pogurschi EN, Popa DC, Dragomir N, Drăgotoiu T, Mihai OD, et al. Antibiotic use in livestock and residues in food – A public health threat: A review. Foods. 2022;11(10). https://doi.org/10.3390/foods11101430
31. Hassan HF, Haddad R, Saidy L, Hosri C, Asmar S, Serhan M. Tracking of enrofloxacin antibiotic in the making of common middle eastern cheeses. Applied Food Research. 2021;1(1). https://doi.org/10.1016/j.afres.2021.100004
32. Sachi S, Ferdous J, Sikder MH, Azizul Karim Hussani SM. Antibiotic residues in milk: Past, present, and future. Journal of Advanced Veterinary and Animal Research. 2019;6(3):315–332. https://doi.org/10.5455/javar.2019.f350
33. Quintanilla P, Beltrán MC, Molina A, Escriche I, Molina MP. Characteristics of ripened Tronchón cheese from raw goat milk containing legally admissible amounts of antibiotics. Journal of Dairy Science. 2019;102(4):2941–2953. https://doi.org/10.3168/jds.2018-15532
34. Gajda A, Nowacka-Kozak E, Gbylik-Sikorska M, Posyniak A. Tetracycline antibiotics transfer from contaminated milk to dairy products and the effect of the skimming step and pasteurisation process on residue concentrations. Food Additives and Contaminants. 2018;35(1):66–76. https://doi.org/10.1080/19440049.2017.1397773
35. Hakk H, Shappell NW, Lupton SJ, Shelver WL, Fanaselle W, Oryang D, et al. Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products. Journal of Agricultural and Food Chemistry. 2016;64(1):326–335. https://doi.org/10.1021/acs.jafc.5b04726
36. Bacanlı M, Başaran N. Importance of antibiotic residues in animal food. Food and Chemical Toxicology. 2019;125:462–466. https://doi.org/10.1016/j.fct.2019.01.033
37. Zhao M, Li X, Zhang Y, Wang Y, Wang B, Zheng L, et al. Rapid quantitative detection of chloramphenicol in milk by microfluidic immunoassay. Food Chemistry. 2021;339. https://doi.org/10.1016/j.foodchem.2020.127857
38. Lupton SJ, Shappell NW, Shelver WL, Hakk H. Distribution of spiked drugs between milk fat, skim milk, whey, curd, and milk protein fractions: Expansion of partitioning models. Journal of Agricultural and Food Chemistry. 2018;66(1):306–314. https://doi.org/10.1021/acs.jafc.7b04463
39. Gbylik-Sikorska M, Gajda A, Nowacka-Kozak E, Posyniak A. The “force” of cloxacillin residue will be with you in various dairy products – The last experimental evidence. Food Control. 2021;121. https://doi.org/10.1016/j.foodcont.2020.107628
40. Lányi K, Darnay L, László N, Lehel J, Friedrich L, Győri R, et al. Transfer of certain beta-lactam antibiotics from cow’s milk to fresh cheese and whey. Food Additives and Contaminants. 2022;39(1):52–60. https://doi.org/10.1080/19440049.2021.1973114
41. Cabizza R, Rubattu N, Salis S, Pes M, Comunian R, Paba A, et al. Transfer of oxytetracycline from ovine spiked milk to whey and cheese. International Dairy Journal. 2017;70:12–17. https://doi.org/10.1016/j.idairyj.2016.12.002
42. Cabizza R, Rubattu N, Salis S, Pes M, Comunian R, Paba A, et al. Impact of a thermisation treatment on oxytetracycline spiked ovine milk: Fate of the molecule and technological implications. LWT. 2018;96:236–243. https://doi.org/10.1016/j.lwt.2018.05.026
43. Rossi R, Saluti G, Moretti S, Diamanti I, Giusepponi D, Galarini R. Multiclass methods for the analysis of antibiotic residues in milk by liquid chromatography coupled to mass spectrometry: A review. Food Additives and Contaminants. 2018;35(2):241–257. https://doi.org/10.1080/19440049.2017.1393107
44. Virto M, Santamarina-García G, Amores G, Hernández I. Antibiotics in dairy production: Where is the problem? Dairy. 2022;3(3):541–564. https://doi.org/10.3390/dairy3030039
45. Quintanilla P, Beltrán MC, Molina MP, Escriche I. Enrofloxacin treatment on dairy goats: Presence of antibiotic in milk and impact of residue on technological process and characteristics of mature cheese. Food Control. 2021;123. https://doi.org/10.1016/j.foodcont.2020.107762
46. Quintanilla P, Doménech E, Escriche I, Beltrán MC, Molina MP. Food safety margin assessment of antibiotics: Pasteurized goat's milk and fresh cheese. Journal of Food Protection. 2019;82(9):1553–1559. https://doi.org/10.4315/0362-028X.JFP-18-434
47. Tilocca B, Costanzo N, Morittu VM, Spina AA, Soggiu A, Britti D, et al. Milk microbiota: Characterization methods and role in cheese production. Journal of Proteomics. 2020;210. https://doi.org/10.1016/j.jprot.2019.103534
48. Fedorova MA. Current trends in milk and dairy products production and consumption in Russia and foreign countries under lockdown conditions. Socio-Economic and Humanitarian Journal. 2022;24(2):3–19. (In Russ.). https://doi.org/10.36718/2500-1825-2022-2-3-19
49. Rezaee M, Khalilian F. Application of ultrasound-assisted extraction followed by solid-phase extraction followed by dispersive liquid-liquid microextraction for the determination of chloramphenicol in chicken meat. Food Analytical Methods. 2018;11:759–767. https://doi.org/10.1007/s12161-017-1048-2
50. Britzi M, Schwartsburd F. Development and validation of a high-throughput method for the determination of eight non-steroidal anti-inflammatory drugs and chloramphenicol in milk, using liquid chromatography-tandem mass spectroscopy. Analytical and Bioanalytical Methods. 2019;1(1). https://doi.org/10.35840/2633-8912/2405
51. Berruga I, Molina MP, Novés' B, Román M, Molina A. In vitro study about the effect of several penicillins during the fermentation of yogurt made from ewe’s milk. Milchwissenschaft. 2007;62(3):303–305.
52. Pastor-Belda M, Campillo N, Arroyo-Manzanares N, Hernández-Córdoba M, Viñas P. Determination of amphenicol antibiotics and their glucuronide metabolites in urine samples using liquid chromatography with quadrupole time-of-flight mass spectrometry. Journal of Chromatography B. 2020;1146. https://doi.org/10.1016/j.jchromb.2020.122122
53. Lekshmi M, Ammini P, Kumar S, Varela MF. The food production environment and the development of antimicrobial resistance in human pathogens of animal origin. Microorganisms. 2017;5(1). https://doi.org/10.3390/microorganisms5010011
54. Mathur S, Singh R. Antibiotic resistance in food lactic acid bacteria – a review. International Journal of Food Microbiology. 2018;105(3):281–295. https://doi.org/10.1016/j.ijfoodmicro.2005.03.008
55. Septimus EJ. Antimicrobial resistance: An antimicrobial/diagnostic stewardship and infection prevention approach. Medical Clinics of North America. 2018;102(5):819–829. https://doi.org/10.1016/j.mcna.2018.04.005
56. Alhaji NB, Aliyu MB, Ghali-Mohammed I, Odetokun IA. Survey on antimicrobial usage in local dairy cows in North-central Nigeria: Drivers for misuse and public health threats. PLoS One. 2019;14(12). https://doi.org/10.1371/journal.pone.0224949
57. What is Antibiotic Resistance? [Internet]. [cited 2022 Dec 25]. Available from: https://amr.biomerieux.com/en/about-amr/what-is-antibiotic-resistance
58. In the wake of antibiotics: what went wrong and how to fix it? [Internet]. [cited 2022 Dec 25]. Available from: https://biomolecula.ru/articles/po-sledam-antibiotikov-chto-moglo-poiti-ne-tak-i-kak-eto-ispravit
59. Yao J, Gao J, Guo J, Wang H, Zhang E, Lin Y, et al. Characterization of bacteria and antibiotic resistance in commercially produced cheeses sold in China. Journal of Food Protection. 2022;85(3):484–493. https://doi.org/10.4315/JFP-21-198
60. Hammad AM, Hassan HA, Shimamoto T. Prevalence, antibiotic resistance and virulence of Enterococcus spp. in Egyptian fresh raw milk cheese. Food Control. 2022;50:815–820. https://doi.org/10.1016/j.foodcont.2014.10.020
61. Brown K, Mugoh M, Call DR, Omulo S. Antibiotic residues and antibiotic-resistant bacteria detected in milk marketed for human consumption in Kibera, Nairobi. PLoS One. 2020;15(5). https://doi.org/10.1371/journal.pone.0233413
62. Zanella GN, Mikcha JMG, Bando E, Siqueira VLD, Machinski Jr M. Occurrence and antibiotic resistance of coliform bacteria and antimicrobial residues in pasteurized cow's milk from Brazil. Journal of Food Protection. 2020;73(9):1684–1687. https://doi.org/10.4315/0362-028x-73.9.1684
63. El Zubeir EM, El Owni OAO. Antimicrobial resistance of bacteria associated with raw milk contaminated by chemical preservatives. World Journal of Dairy and Food Sciences. 2009;4(1):65–69.