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Veterinary sciences2022; 9(1); doi: 10.3390/vetsci9010024

Ivermectin (IVM) Possible Side Activities and Implications in Antimicrobial Resistance and Animal Welfare: The Authors’ Perspective.

Abstract: Ivermectin has a wide number of many diverse functions. Certainly, it is irreplaceable for the treatment of parasitic pathologies in both human and veterinary medicine, and the latter represents the major field of its application. It has been called the "drug for the world's poor" because of its role as a saviour for those living on the margins of society, in underdeveloped areas afflicted by devastating and debilitating diseases, such as Onchocerciasis and Lymphatic filariasis. It showed huge, unexpected potential as an antibacterial (Chlamydia trachomatis and mycobacteria), and it has antiviral and anti-inflammatory properties. The research line described here is placed right in the middle of the investigation on the impact of this drug as an antimicrobial and an immunomodulator. Being a drug widely employed for mass administration, it is mandatory to broaden the knowledge of its possible interaction with bacterial growth and its generation of antimicrobial resistance. Equally, it is important to understand the impact of these drugs on the immune systems of animal species, e.g., horses and dogs, in which this drug is often used. More importantly, could immunomodulation and antibacterial activity promote both bacterial growth and the occurrence of resistance mechanisms?
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Publication Date: 2022-01-11 PubMed ID: 35051108PubMed Central: PMC8777850DOI: 10.3390/vetsci9010024Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores the different therapeutic functions of ivermectin. It further investigates the drug’s impact as an antimicrobial, an immunomodulator, as well as its potential role in generating antimicrobial resistance. The article also emphasizes the need to study the effects of this drug on the immune systems of animals.

Purpose of the Study

  • The aim of this research is to delve into the various potential functions of the drug ivermectin.
  • The study seeks to evaluate ivermectin’s roles as an antimicrobial, antibacterial, antiviral, and anti-inflammatory agent.
  • The research scrutinizes ivermectin’s possible interaction with bacterial growth and its potential generation of antimicrobial resistance.
  • It also aims to understand the drug’s impact on the immune systems of animals, particularly species such as horses and dogs, where ivermectin is commonly used.

Significance and Potential Impact of the Study

  • The study is significant as it could expand our understanding of ivermectin’s various therapeutic functions, ones that go beyond its well-documented role in treating parasitic diseases.
  • By investigating the potential for an antimicrobial effect, the research opens up the possibility of ivermectin being used to combat bacterial infections.
  • The study might shed light on potential downsides of widespread ivermectin use, such as the possible generation of antimicrobial resistance, which could have substantial implications for both human and animal health.
  • Finding out more about ivermectin’s impact on the immune systems of animals might lead to improvements in veterinary treatments and animal health outcomes.
  • Understanding the role of ivermectin as both an immunomodulator and antibacterial could help identify whether these functions might inadvertently promote bacterial growth and antimicrobial resistance,

Key Investigation Areas

  • The research investigates ivermectin’s potential antibacterial capabilities, including against Chlamydia trachomatis and mycobacteria.
  • The study also focuses on possible contributions of ivermectin to antimicrobial resistance, especially as the medication is widely used in mass administration.
  • The research seeks to inherently understand the drug’s impacts on the immune systems of various animal species, especially horses and dogs, where the application of ivermectin is frequently used.
  • It looks into the possibility whether immunomodulation and antibacterial properties of the drug could promote bacterial growth and the emergence of resistance mechanisms.

Cite This Article

APA
Piras C, Gugliandolo E, Castagna F, Palma E, Britti D. (2022). Ivermectin (IVM) Possible Side Activities and Implications in Antimicrobial Resistance and Animal Welfare: The Authors’ Perspective. Vet Sci, 9(1). https://doi.org/10.3390/vetsci9010024

Publication

Veterinary sciences
ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 9
Issue: 1

Researcher Affiliations

Piras, Cristian
  • Department of Health Sciences, Campus Universitario "S. Venuta", University "Magna Græcia" of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
Gugliandolo, Enrico
  • Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy.
Castagna, Fabio
  • Department of Health Sciences, Campus Universitario "S. Venuta", University "Magna Græcia" of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
Palma, Ernesto
  • Department of Health Sciences, Campus Universitario "S. Venuta", University "Magna Græcia" of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
  • Nutramed S.c.a.r.l. Complesso Ninì Barbieri, Roccelletta di Borgia, 88021 Catanzaro, Italy.
  • Department of Health Sciences, Institute of Research for Food Safety & Health (IRC-FISH), University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy.
Britti, Domenico
  • Department of Health Sciences, Campus Universitario "S. Venuta", University "Magna Græcia" of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 36 references
  1. Crump A, Ōmura S. Ivermectin, 'wonder drug' from Japan: the human use perspective.. Proc Jpn Acad Ser B Phys Biol Sci 2011;87(2):13-28.
    doi: 10.2183/pjab.87.13pmc: PMC3043740pubmed: 21321478google scholar: lookup
  2. Crump A. Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations.. J Antibiot (Tokyo) 2017 May;70(5):495-505.
    doi: 10.1038/ja.2017.11pubmed: 28196978google scholar: lookup
  3. Guo J, Ma R, Su B, Li Y, Zhang J, Fang J. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs).. Sci Rep 2016 May 16;6:25949.
    doi: 10.1038/srep25949pmc: PMC4867605pubmed: 27181521google scholar: lookup
  4. Sutherland IH. Veterinary use of ivermectin.. Acta Leiden 1990;59(1-2):211-6.
    pubmed: 2198752
  5. Lim LE, Vilchèze C, Ng C, Jacobs WR Jr, Ramón-García S, Thompson CJ. Anthelmintic avermectins kill Mycobacterium tuberculosis, including multidrug-resistant clinical strains.. Antimicrob Agents Chemother 2013 Feb;57(2):1040-6.
    doi: 10.1128/AAC.01696-12pmc: PMC3553693pubmed: 23165468google scholar: lookup
  6. Pettengill MA, Lam VW, Ollawa I, Marques-da-Silva C, Ojcius DM. Ivermectin inhibits growth of Chlamydia trachomatis in epithelial cells.. PLoS One 2012;7(10):e48456.
    doi: 10.1371/journal.pone.0048456pmc: PMC3484050pubmed: 23119027google scholar: lookup
  7. Blakley BR, Rousseaux CG. Effect of ivermectin on the immune response in mice.. Am J Vet Res 1991 Apr;52(4):593-5.
    pubmed: 1828942
  8. Omer MO, Ashraf M, Javeed A, Maqbool A. Immunostimulatory effect of ivermectin on macrophage engulfment and delayed type hypersensitivity in broilers. J. Anim. Plant Sci. 2012;22:250–255.
  9. Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen.. J Antibiot (Tokyo) 2020 Sep;73(9):593-602.
    doi: 10.1038/s41429-020-0336-zpmc: PMC7290143pubmed: 32533071google scholar: lookup
  10. Ianaro A, Ialenti A, Maffia P, Sautebin L, Rombolà L, Carnuccio R, Iuvone T, D'Acquisto F, Di Rosa M. Anti-inflammatory activity of macrolide antibiotics.. J Pharmacol Exp Ther 2000 Jan;292(1):156-63.
    pubmed: 10604943
  11. Terao H, Asano K, Kanai K, Kyo Y, Watanabe S, Hisamitsu T, Suzaki H. Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice.. Mediators Inflamm 2003 Aug;12(4):195-202.
    doi: 10.1080/09629350310001599620pmc: PMC1781621pubmed: 14514469google scholar: lookup
  12. Ivetić Tkalcević V, Bosnjak B, Hrvacić B, Bosnar M, Marjanović N, Ferencić Z, Situm K, Culić O, Parnham MJ, Eraković V. Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.. Eur J Pharmacol 2006 Jun 6;539(1-2):131-8.
    doi: 10.1016/j.ejphar.2006.03.074pubmed: 16698012google scholar: lookup
  13. Viktorov AV, Yurkiv VA. Effect of ivermectin on function of liver macrophages.. Bull Exp Biol Med 2003 Dec;136(6):569-71.
    doi: 10.1023/B:BEBM.0000020206.23474.e9pubmed: 15500074google scholar: lookup
  14. Viktorov AV. [Ivermectin inhibits activation of Kupffer cells induced by lipopolysaccharide toxin].. Antibiot Khimioter 2003;48(4):3-6.
    pubmed: 13677129
  15. Zhang X, Song Y, Ci X, An N, Ju Y, Li H, Wang X, Han C, Cui J, Deng X. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice.. Inflamm Res 2008 Nov;57(11):524-9.
    doi: 10.1007/s00011-008-8007-8pubmed: 19109745google scholar: lookup
  16. Campbell WC. Ivermectin: an update.. Parasitol Today 1985 Jul;1(1):10-6.
    doi: 10.1016/0169-4758(85)90100-0pubmed: 15275618google scholar: lookup
  17. Davies HG, Green RH. Avermectins and milbemycins.. Nat Prod Rep 1986 Apr;3(2):87-121.
    doi: 10.1039/np9860300087pubmed: 3526202google scholar: lookup
  18. Blair LS, Campbell WC. Efficacy of avermectin B1a against microfilariae of Dirofilaria immitis.. Am J Vet Res 1979 Jul;40(7):1031-2.
    pubmed: 507489
  19. Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent.. Science 1983 Aug 26;221(4613):823-8.
    doi: 10.1126/science.6308762pubmed: 6308762google scholar: lookup
  20. Piras C, Soggiu A, Bonizzi L, Nally J, Greco V, Urbani A, Martino PA, Roncada P. 2D DIGE comparative analysis of Escherichia coli strains with induced resistance to enrofloxacin. Farm Animal Proteomics 2013; pp. 147–150.
    doi: 10.3920/978-90-8686-776-9_39google scholar: lookup
  21. Piras C, Soggiu A, Greco V, Martino PA, Del Chierico F, Putignani L, Urbani A, Nally JE, Bonizzi L, Roncada P. Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog.. J Proteomics 2015 Sep 8;127(Pt B):365-76.
    doi: 10.1016/j.jprot.2015.05.040pubmed: 26066767google scholar: lookup
  22. Eldholm V, Monteserin J, Rieux A, Lopez B, Sobkowiak B, Ritacco V, Balloux F. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain.. Nat Commun 2015 May 11;6:7119.
    doi: 10.1038/ncomms8119pmc: PMC4432642pubmed: 25960343google scholar: lookup
  23. Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V, Shea TP, Walker BJ, Bantubani N, Almeida DV, Alvarado L, Chapman SB, Mvelase NR, Duffy EY, Fitzgerald MG, Govender P, Gujja S, Hamilton S, Howarth C, Larimer JD, Maharaj K, Pearson MD, Priest ME, Zeng Q, Padayatchi N, Grosset J, Young SK, Wortman J, Mlisana KP, O'Donnell MR, Birren BW, Bishai WR, Pym AS, Earl AM. Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal.. PLoS Med 2015 Sep;12(9):e1001880.
    doi: 10.1371/journal.pmed.1001880pmc: PMC4587932pubmed: 26418737google scholar: lookup
  24. Piras C, Greco V, Gugliandolo E, Soggiu A, Tilocca B, Bonizzi L, Zecconi A, Cramer R, Britti D, Urbani A, Roncada P. Raw Cow Milk Bacterial Consortium as Bioindicator of Circulating Anti-Microbial Resistance (AMR).. Animals (Basel) 2020 Dec 11;10(12).
    doi: 10.3390/ani10122378pmc: PMC7763537pubmed: 33322611google scholar: lookup
  25. Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter JJ. Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study.. Chest 2021 Jan;159(1):85-92.
    doi: 10.1016/j.chest.2020.10.009pmc: PMC7550891pubmed: 33065103google scholar: lookup
  26. Stankiewicz M, Cabaj W, Jonas WE, Moore LG, Millar K, Ng Chie W. Influence of ivermectin on cellular and humoral immune responses of lambs.. Vet Immunol Immunopathol 1995 Feb;44(3-4):347-58.
    doi: 10.1016/0165-2427(94)05308-Fpubmed: 7747411google scholar: lookup
  27. Sajid MS, Iqbal Z, Muhammad G, Iqbal MU. Immunomodulatory effect of various anti-parasitics: a review.. Parasitology 2006 Mar;132(Pt 3):301-13.
    doi: 10.1017/S0031182005009108pubmed: 16332285google scholar: lookup
  28. Gupta D, Sahoo AK, Singh A. Ivermectin: potential candidate for the treatment of Covid 19.. Braz J Infect Dis 2020 Jul-Aug;24(4):369-371.
    doi: 10.1016/j.bjid.2020.06.002pmc: PMC7321032pubmed: 32615072google scholar: lookup
  29. Berge T, Eriksson A, Brorson IS, Høgestøl EA, Berg-Hansen P, Døskeland A, Mjaavatten O, Bos SD, Harbo HF, Berven F. Quantitative proteomic analyses of CD4(+) and CD8(+) T cells reveal differentially expressed proteins in multiple sclerosis patients and healthy controls.. Clin Proteomics 2019;16:19.
    doi: 10.1186/s12014-019-9241-5pmc: PMC6505067pubmed: 31080378google scholar: lookup
  30. Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis.. Nat Methods 2009 May;6(5):359-62.
    doi: 10.1038/nmeth.1322pubmed: 19377485google scholar: lookup
  31. Couch CE, Arnold HK, Crowhurst RS, Jolles AE, Sharpton TJ, Witczak MF, Epps CW, Beechler BR. Bighorn sheep gut microbiomes associate with genetic and spatial structure across a metapopulation.. Sci Rep 2020 Apr 20;10(1):6582.
    doi: 10.1038/s41598-020-63401-0pmc: PMC7171152pubmed: 32313214google scholar: lookup
  32. Kolmogorov M, Bickhart DM, Behsaz B, Gurevich A, Rayko M, Shin SB, Kuhn K, Yuan J, Polevikov E, Smith TPL, Pevzner PA. metaFlye: scalable long-read metagenome assembly using repeat graphs.. Nat Methods 2020 Nov;17(11):1103-1110.
    doi: 10.1038/s41592-020-00971-xpubmed: 33020656google scholar: lookup
  33. Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M, Edalatmand A, Huynh W, Nguyen AV, Cheng AA, Liu S, Min SY, Miroshnichenko A, Tran HK, Werfalli RE, Nasir JA, Oloni M, Speicher DJ, Florescu A, Singh B, Faltyn M, Hernandez-Koutoucheva A, Sharma AN, Bordeleau E, Pawlowski AC, Zubyk HL, Dooley D, Griffiths E, Maguire F, Winsor GL, Beiko RG, Brinkman FSL, Hsiao WWL, Domselaar GV, McArthur AG. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database.. Nucleic Acids Res 2020 Jan 8;48(D1):D517-D525.
    doi: 10.1093/nar/gkz935pmc: PMC7145624pubmed: 31665441google scholar: lookup
  34. Piras C, Soggiu A, Greco V, Nally J, Urbani A, Anna P, Drigo M, Roncada P. Mechanisms of Enrofloxacin Antibiotic Resistance in Zoonotic E. coli. .
  35. Castagna F, Britti D, Oliverio M, Bosco A, Bonacci S, Iriti G, Ragusa M, Musolino V, Rinaldi L, Palma E, Musella V. In Vitro Anthelminthic Efficacy of Aqueous Pomegranate (Punica granatum L.) Extracts against Gastrointestinal Nematodes of Sheep.. Pathogens 2020 Dec 18;9(12).
    doi: 10.3390/pathogens9121063pmc: PMC7766728pubmed: 33353177google scholar: lookup
  36. Castagna F, Piras C, Palma E, Musolino V, Lupia C, Bosco A, Rinaldi L, Cringoli G, Musella V, Britti D. Green Veterinary Pharmacology Applied to Parasite Control: Evaluation of Punica granatum, Artemisia campestris, Salix caprea Aqueous Macerates against Gastrointestinal Nematodes of Sheep.. Vet Sci 2021 Oct 15;8(10).
    doi: 10.3390/vetsci8100237pmc: PMC8539373pubmed: 34679067google scholar: lookup

Citations

This article has been cited 8 times.
  1. Castagna F, Bava R, Musolino V, Piras C, Cardamone A, Carresi C, Lupia C, Bosco A, Rinaldi L, Cringoli G, Palma E, Musella V, Britti D. Potential New Therapeutic Approaches Based on Punica granatum Fruits Compared to Synthetic Anthelmintics for the Sustainable Control of Gastrointestinal Nematodes in Sheep. Animals (Basel) 2022 Oct 21;12(20).
    doi: 10.3390/ani12202883pubmed: 36290268google scholar: lookup
  2. Kim S, Sayem SAJ, Chae H, Park SW, Gui L, Park SC, Kang J. Comparative pharmacokinetic and bioequivalence of nine oral ivermectin formulations in dogs. J Vet Sci 2025 Nov;26(6):e88.
    doi: 10.4142/jvs.25170pubmed: 41332008google scholar: lookup
  3. Gernandt N, Wentzel C, van Staden D, Liebenberg W, Lemmer HJR, Gerber M. Therapeutic and Formulation Advances of Ivermectin in Veterinary and Human Medicine. Pharmaceutics 2025 Oct 25;17(11).
    doi: 10.3390/pharmaceutics17111384pubmed: 41304722google scholar: lookup
  4. Ali RA, Amin YA, Mar'ie ZA, Mosa AM, Mobarak SA. Ameliorative effect of folic acid and vitamin B12 against Ivermectin-induced hepatotoxicity, renal toxicity, oxidative stress and immunohistochemical changes in male albino rats. Sci Rep 2025 Oct 31;15(1):38107.
    doi: 10.1038/s41598-025-23047-2pubmed: 41174151google scholar: lookup
  5. Golenser J, Birman I, Gold D. Considering ivermectin for treatment of schistosomiasis. Parasitol Res 2024 Apr 9;123(4):180.
    doi: 10.1007/s00436-024-08178-1pubmed: 38592544google scholar: lookup
  6. Kim S, Chae H, Lee EB, Lee G, Park SC, Kang J. Comparative Pharmacokinetics and Bioequivalence of Pour-On Ivermectin Formulations in Korean Hanwoo Cattle. Antibiotics (Basel) 2023 Dec 19;13(1).
    doi: 10.3390/antibiotics13010003pubmed: 38275313google scholar: lookup
  7. Liu L, Mahalak KK, Bobokalonov JT, Narrowe AB, Firrman J, Lemons JMS, Bittinger K, Hu W, Jones SM, Moustafa AM. Impact of Ivermectin on the Gut Microbial Ecosystem. Int J Mol Sci 2023 Nov 9;24(22).
    doi: 10.3390/ijms242216125pubmed: 38003317google scholar: lookup
  8. Oppedisano F, De Fazio R, Gugliandolo E, Crupi R, Palma E, Abbas Raza SH, Tilocca B, Merola C, Piras C, Britti D. Mediterranean Plants with Antimicrobial Activity against Staphylococcus aureus, a Meta-Analysis for Green Veterinary Pharmacology Applications. Microorganisms 2023 Sep 9;11(9).
    doi: 10.3390/microorganisms11092264pubmed: 37764109google scholar: lookup
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