Effectiveness and safety of therapeutics used for treatment of experimental or spontaneous Mycoplasma infections

Mycoplasmoses of cattle and small ruminants,  pigs and poultry are widely spread and the infection process is frequently associated with other diseases. Mycoplasma spp. cause inflammatory respiratory diseases, diseases of joints and meninges, keratoconjunctivitis, mastitis and endometritis,  abortion and stillbirths. Etiotropic therapy of mycoplasmal infections consists in prescribing antibiotics: enrofloxacin, difloxacin, oxytetracycline, chlortetracycline, doxycycline, tylosin, tilmicosin, tylvalosin, tiamulin, florfenicol, lincomycin, spectinomycin, tulathromycin. The results of studies described in different publications show high sensitivity of Mycoplasma synoviae and Mycoplasma gallisepticum to tetracyclines, tiamulin and tylvalosin. Isolates with increased resistance to tilmicosin are also resistant to tylosin and lincomycin. Treatment of respiratory infections in lambs, the main causative agents  of which are Mannheimia haemolytica and Mycoplasma, has been successful with the use of fluoroquinolones, tilmicosin, tulathromycin, chlortetracycline, enrofloxacin, doxycycline, and oxytetracycline. Isolates of Mycoplasma bovis are largely sensitive to oxytetracycline, florfenicol and tulathromycin.  Enrofloxacin has a less pronounced therapeutic effect. Tilmicosin and oxytetracycline are effective in the treatment of respiratory diseases of young cattle, associated with Mycoplasma spp. Tulathromycin and tilmicosin have a significant therapeutic effect in the treatment of pneumonia in weaned piglets experimentally infected with Mycoplasma hyopneumoniae. Multiple (course) use of enrofloxacin significantly increases the therapeutic effect. Tilmicosin is effective in the control of other bacterial infections of pigs (pasteurellosis, streptococcosis, hemophilic polyserositis, infectious atrophic rhinitis).The general prophylaxis of mycoplasmal infections is to comply with veterinary and sanitary standards and to implement quarantine measures in the infection outbreak.

1. Rosales R. S., Puleio R., Loria G. R., Catania S., Nicholas R. A. J. Mycoplasmas: Brain invaders? Res. Vet. Sci. 2017; 113: 56–61. DOI: 10.1016/j.rvsc.2017.09.006.

2. EI-Jakee J., Elshamy S., Hassan A.-W., Abdelsalam M., Younis N., El-Hady M. A., Eissa A. E. Isolation and characterization of Mycoplasmas from some moribund Egyptian fishes. Aquacult. Int. 2020; 28: 901–912. DOI: 10.1007/s10499-019-00502-2.

3. Morrow C. J., Kreizinger Z., Achari R. R., Bekő K., Yvon C., Gyuranecz M. Antimicrobial susceptibility of pathogenic mycoplasmas in chickens in Asia. Vet. Microbiol. 2020; 250:108840. DOI: 10.1016/j.vetmic.2020.108840.

4. Yadav J. P., Tomar P., Singh Y., Khurana S. K. Insights on Mycoplasma gallisepticum and Mycoplasma synoviae infection in poultry: a systematic review. Animal Biotechnology. 2021; DOI: 10.1080/10495398.2021.1908316.

5. Gerchman I., Levisohn S., Mikula I., Manso-Silván L., Lysnyansky I. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry. Vet. Res. 2011; 42 (1):90. DOI: 10.1186/1297-9716-42-90.

6. Bergonier D., Berthelot X., Poumarat F. Contagious agalactia of small ruminants: current knowledge concerning epidemiology, diagnosis and control. Rev. Sci. Tech. 1997; 16 (3): 848–873. DOI: 10.20506/rst.16.3.1062.

7. Ghanem M. E., Higuchi H., Tezuka E., Ito H., Devkota B., Izaike Y., Osawa T. Mycoplasma infection in the uterus of early postpartum dairy cows and its relation to dystocia and endometritis. Theriogenology. 2013; 79 (1): 180–185. DOI: 10.1016/j.theriogenology.2012.09.027.

8. Bergonier D., Poumarat F. Agalactie contagieuse des petits ruminants: épidémiologie, diagnostic et contrôle = Contagious agalactia of small ruminants: epidemiology, diagnosis and control. Rev. Sci. Tech. 1996; 15 (4): 1431–1475. PMID: 9527414. (in French)

9. De Almeida J. F., do Nascimento E. R., de Almeida Pereira V. L., Barreto M. L., de Martino Campos C. A., de Azevedo E. O. Polimerase chain reaction (PCR) in the diagnosis of goat mycoplasmosis proceeding from cultures stored in glycerol. Rev. Bras. Med. Vet. 2007; 29 (2): 54–57.

10. Politis A. P., Vasileiou N. G. C., Ioannidi K. S., Mavrogianni V. S. Treatment of bacterial respiratory infections in lambs. Small Ruminant Research. 2019; 176: 70–75. DOI: 10.1016/j.smallrumres.2019.05.005.

11. Hegde Shivanand, Hegde Shrilakshmi, Spergser J., Brunthaler R., Rosengarten R., Chopra-Dewasthaly R. In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model. Int. J. Med. Microbiol. 2014; 304 (8): 1024–1231. DOI: 10.1016/j.ijmm.2014.07.011.

12. Ambroset C., Pau-Roblot C., Game Y., Gaurivaud P., Tardy F. Identification and characterization of Mycoplasma feriruminatoris sp. nov. strains isolated from Alpine ibex: A 4th species in the Mycoplasma mycoides cluster hosted by non-domesticated ruminants? Front. Microbiol. 2017; 8:939. DOI: 10.3389/fmicb.2017.00939.

13. McKelvie J., Morgan J. H., Nanjiani I. A., Sherington J., Rowan T. G., Sunderland S. J. Evaluation of tulathromycin for the treatment of pneumonia following experimental infection of swine with Mycoplasma hyopneumoniae. Veterinary Therapeutics. 2005; 6 (2): 197–202. PMID: 16094566.

14. Tortorelli G., Carrillo Gaeta N., Mendonça Ribeiro B. L., Miranda Marques L., Timenetsky J., Gregory L. Evaluation of Mollicutes microorganisms in respiratory disease of cattle and their relationship to clinical signs. J. Vet. Intern. Med. 2017; 31 (4): 1215–1220. DOI: 10.1111/jvim.14721.

15. Dacak D., Petters J., Batista-Cirne L., Lucero M., Aliendre R., Guzmán J., Ordoñez R. Primer reporte de micoplasmosis en Procyon cancrivorus en cautiverio en Asunción, Paraguay. Rev. Inv. Vet. Perú. 2021; 32 (1):e19494. DOI: 10.15381/RIVEP.V32I1.19494.

16. Crossland N. A., DiGeronimo P. M., Sokolova Y., Childress A. L., Wellehan J. F. X. Jr, Nevarez J., Paulsen D. Pneumonia in a captive central bearded dragon with concurrent detection of helodermatid adenovirus 2 and a novel Mycoplasma species. Vet. Pathol. 2018; 55 (6): 900–904. DOI: 10.1177/0300985818780451.

17. Macêdo A. A. M., Oliveira J. M. B., Silva B. P., Borges J. M., Soares L. B. F., Silva G. M., et al. Occurrence of Mycoplasma bovigenitalium and Ureaplasma diversum in dairy cattle from to Pernambuco state, Brazil. Arq. Bras. Med. Vet. Zootec. 2018; 70 (6): 1798–1806. DOI: 10.1590/1678-4162-10132.

18. Al-Farha A. A., Hemmatzadeh F., Khazandi M., Hoare A., Petrovski K. Evaluation of effects of Mycoplasma mastitis on milk composition in dairy cattle from South Australia. BMC Vet. Res. 2017; 13 (1):351. DOI: 10.1186/s12917-017-1274-2.

19. Eissa S. I., Hassan A. M., Hashem Y. M., Shaker M. M. Comparative molecular study of Mycoplasma bovis isolates from Egyptian buffaloes and cows suffered from mastitis. European J. Biol. Sci. 2012; 4 (4): 114–120. DOI: 10.5829/idosi.ejbs.2012.4.4.6668.

20. Eissa S., Hashem Y., Abo-Shama U. H., Shaker M. Sequence analysis of three genes of Mycoplasma bovis isolates from Egyptian cattle and buffaloes. Microbiol. Res. J. Int. 2016; 14 (3): 1–10. DOI: 10.9734/BMRJ/2016/25014.

21. Fox L. K. Mycoplasma mastitis: causes, transmission, and control. Vet. Clin. North Am. Food Anim. Pract. 2012; 28 (2): 225–237. DOI: 10.1016/j.cvfa.2012.03.007.

22. Nicholas R. A., Ayling R. D. Mycoplasma bovis: disease, diagnosis, and control. Res. Vet. Sci. 2003; 74 (2): 105–112. DOI: 10.1016/s0034-5288(02)00155-8.

23. Pothmann H., Spergser J., Elmer J., Prunner I., Iwersen M., Klein-Jöbstl D., Drillich M. Severe Mycoplasma bovis outbreak in an Austrian dairy herd. J. Vet. Diagn. Invest. 2015; 27 (6): 777–783. DOI: 10.1177/1040638715603088.

24. Media releases on the Mycoplasma bovis response. Available at: https://www.biosecurity.govt.nz/protection-and-response/mycoplasma-bovis/resources-for-mycoplasma-bovis/media-releases.

25. Saraya T. The history of Mycoplasma pneumoniae pneumonia. Front. Microbiol. 2016; 7:364. DOI: 10.3389/fmicb.2016.00364.

26. Surýnek J., Vrtková I., Knoll A. Mycoplasma bovis was not detected in milk from dairy cattle in the Czech Republic. Acta Univ. Agric. Silvic. Mendelianae Brun. 2016; 64 (1): 165–168. DOI: 10.11118/actaun201664010165.

27. Arcangioli M. A., Chazel M., Sellal E., Botrel M. A., Bezille P., Poumarat F., et al. Prevalence of Mycoplasma bovis udder infection in dairy cattle: preliminary field investigation in southeast France. New Zealand Veterinary Journal. 2011; 59 (2): 75–78. DOI: 10.1080/00480169.2011.552856.

28. Bednarek D., Ayling R. D., Nicholas R. A., Dudek K., Szymańska-Czerwinska M. Serological survey to determine the occurrence of respiratory Mycoplasma infections in the Polish cattle population. Vet. Rec. 2012; 171 (2):45. DOI: 10.1136/vr.100545.

29. Calcutt M. J., Lysnyansky I., Sachse K., Fox L. K., Nicholas R. A. J., Ayling R. D. Gap analysis of Mycoplasma bovis disease, diagnosis and control: An aid to identify future development requirements. Transbound. Emerg. Dis. 2018; 65 (Suppl 1): 91–109. DOI: 10.1111/tbed.12860.

30. Step D. L., Kirkpatrick J. G. Mycoplasma infection in cattle. Pneumonia – arthritis syndrome. The Bovine Practitioner. 2001; 35 (2): 149–155. DOI: 10.21423/bovine-vol35no2p149-155.

31. Hendrick S. H., Bateman K. G., Rosengren L. B. The effect of antimicrobial treatment and preventive strategies on bovine respiratory disease and genetic relatedness and antimicrobial resistance of Mycoplasma bovis isolates in a western Canadian feedlot. Can. Vet. J. 2013; 54 (12): 1146–1156. PMID: 24293675.

32. Musser J., Mechor G. D., GröhnY.T., Dubovi E. J., Shin S. Comparison of tilmicosin with long-acting oxytetracycline for treatment of respiratory tract disease in calves. J. Am. Vet. Med.Assoc. 1996; 208 (1): 102–106. PMID: 8682696.

33. Robb E. J., Tucker C. M., Corley L., Bryson W. L., Rogers K. C., Sturgess K., et al. Efficacy of tulathromycin or enrofloxacin for initial treatment of naturally occurring bovine respiratory disease in feeder calves. Veterinary Therapeutics. 2007; 8 (2): 127–135. PMID: 17616947.

34. Greene C. E., Chalker V. J. Nonhemotropic Mycoplasmal, Ureaplasmal and L-Form Infections. In: Infectious diseases of the Dog and Cat. Ed. C. E. Greene. 4th ed. St Louis: Elsevier Inc.; 2011; 319–325.

35. Haapala V., Pohjanvirta T., Vähänikkilä N., Halkilahti J., Simonen H., Pelkonen S., et al. Semen as a source of Mycoplasma bovis mastitis in dairy herds. Vet. Microbiol. 2018; 216: 60–66. DOI: 10.1016/j.vetmic.2018.02.005.

36. Clark L. K., Wu C. C., Alstine W. G., Knox K. E. Evaluation of the effectiveness of a macrolide antibiotic on reduction of respiratory pathogens in 12-day and 21-day weaned pigs. J. Swine Health Prod. 1998; 6 (6): 257–262.

37. Mosier D. Review of BRD pathogenesis: the old and the new. Anim. Health Res. Rev. 2014; 15 (2): 166–168. DOI: 10.1017/S1466252314000176.

38. Mustafa R., Qi J., Ba X., Chen Y., Hu C., Liu X., et al. In vitro quinolones susceptibility analysis of Chinese Mycoplasma bovis isolates and their phylogenetic scenarios based upon QRDRs of DNA topoisomerases revealing a unique transition in ParC. Pak. Vet. J. 2013; 33 (3): 364–369.

39. Zhang X. H., Pan J. Z., Wu N., Tang S., Lei X. D., Sun Y. Y. et al. Investigation of the efficiency and safety of tilmicosin phosphate in treating experimental mycoplasmal infections in pigs. Turk. J. Vet. Anim. Sci. 2018; 42 (6): 571–580. DOI: 10.3906/vet-1804-76.

40. MacInnes J. I., Paradis M. A., Vessie G. H., Slavic L., Watson S., Wilson J. B., et al. Efficacy of prophylactic tilmicosin in the control of experimentally induced Haemophilus parasuis infection in pigs. J. Swine Health Prod. 2003; 11 (4): 174–180.

41. Olson L. B., Bäckström L. R. The effect of tilmicosin in minimizing atrophic rhinitis, pneumonia, and pleuritis in swine. J. Swine Health Prod. 2000; 8 (6): 263–268.