Potential of current antibacterial therapy in patients with urethritis due to sexually transmitted diseases

Urethritis is among the most common urological diseases in men. In the Russian Federation, approximately 350,000 cases of non-gonococcal urethritis are reported each year, which accounts for up to 65% of all inflammatory diseases of the genitourinary (GU) system. In recent years, the global medical community has faced a serious challenge of significantly increased spreading of antibiotic resistance among these microorganisms. The mechanisms acquired by intracellular pathogens to counteract the effect of antibiotics is of particular concern. This phenomenon significantly limits the effectiveness of standard empirical treatment regimens and urges healthcare professionals to discover and clinically implement alternative antibacterial approaches. This review summarizes data on current approaches to antibacterial therapy for urethritis. The authors used peer-reviewed sources from PubMed/MEDLINE, eLIBRARY.RU, Cochrane Library, and Google Scholar, as well as national and international clinical guidelines and recommendations. In total, 79 sources (review articles and original studies among the number) were included. As the results are heterogeneous, the authors used descriptive (narrative) synthesis in the review. A clinical case included as an authors' own observation from real-world clinical practice demonstrates the potential of current antibacterial therapy in a patient with a mixed infection and concomitant organic pathology resulted from gonococcal urethritis. Josamycin maintains activity with the growth of macrolide resistance. The drug has minimal side effects and is approved for use in pregnant women and children. For this reason, Josamycin is considered an effective and safe alternative in urogenital infections, particularly in the presence of multidrug-resistant bacteria. In the context of the above-mentioned issues, Josamycin retains its position as one of the few macrolide antibiotics demonstrating high activity against key urogenital pathogens, such as Mycoplasma genitalium, Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis.

1. Apolikhin OI, Sivkov AV, Komarova VA, Nikushina AA. Prostate diseases in the Russian Federation: statistical data for 2008-2017. Experimental and Clinical Urology. 2019;(2):4–13. (In Russ.) https://doi.org/10.29188/2222-8543-2019-11-2-4-12.

2. Schuppe HC, Pilatz A, Meinhardt A, Behre HM. Infections and Inflammation of the Seminal Ducts and Accessory Sex Glands. In: Nieschlag E, Behre HM, Kliesch S, Nieschlag S (eds.). Andrology: Male Reproductive Health and Dysfunction. Cham: Springer International Publishing; 2023, pp. 353–371. https://doi.org/10.1007/978-3-031-31574-9_26.

3. Andreeva IV, Stetsyuk OU, Korolev SV, Kozlov SN. Nongonococcal urethritis in men: current views on etiology and approaches to treatment. Lechaschi Vrach. 2010;(8):24–31. (In Russ.) Available at: https://www.lvrach.ru/2010/08/15398302.

4. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187. https://doi.org/10.15585/mmwr.rr7004a1.

5. Wagenlehner FM, Brockmeyer NH, Discher T, Friese K, Wichelhaus TA. The Presentation, Diagnosis, and Treatment of Sexually Transmitted Infections. Dtsch Arztebl Int. 2016;113(1-2):11–22. https://doi.org/10.3238/arztebl.2016.0011.

6. Elder K, Baker DJ, Ribes JA. Infections, infertility, and assisted reproduction. Cambridge University Press; 2004. https://doi.org/10.1017/CBO9780511545139.

7. Shibuki S, Saida T, Hoshiai S, Ishiguro T, Sakai M, Amano T et al. Imaging findings in inflammatory disease of the genital organs. Jpn J Radiol. 2024;42(4):331–346. https://doi.org/10.1007/s11604-023-01518-8.

8. Alatorskykh AY, Fedorych PV, Koval SB, Kuts TV. Treatment of combined acne and genitourinary infections caused by Cchlamydia and Mycoplasmas. Wiad Lek. 2023;76(8):1725–1729.Available at: https://pubmed.ncbi.nlm.nih.gov/37740962/.

9. Naber KG. Urinary tract infection in men, including prostatitis, epididymitis, non-specific urethritis and Reiter’s syndrome. Curr Opin Infect Dis. 1994;7(1):9–19. https://doi.org/10.1097/00001432-199402000-00003.

10. Bébéar CM, de Barbeyrac B, Pereyre S, Renaudin H, Clerc M, Bébéar C. Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis. Clin Microbiol Infect. 2008;14(8):801–805. https://doi.org/10.1111/j.1469-0691.2008.02027.x.

11. Edelstein IA, Gushchin AE, Gladin DP, Romanov AV, Negasheva ES, Frigo NV et al. High prevalence of resistance to macrolides and fluoroquinolones in Mycoplasma genitalium isolated from patients in two Russian megalopolises – Moscow and St. Petersburg in 2021–2024. Klinicheskaia Mikrobiologiia i Antimikrobnaia Khimioterapiia. 2024;26(3):356–369. (In Russ.) Available at: https://cmac-journal.ru/publication/2024/3/cmac-2024-t26-n3-p356/.

12. Портнягина ЕВ, Раднаев ГГ. Рациональная антибактериальная терапия и вопросы предупреждения бактериальной резистентности. Иркутск: Иркутский государственный медицинский университет; 2022. 135 c. Режим доступа: https://irkgmu.ru/src/downloads/3fe51fc9_ab_portnyagina_e.v._uch_pos_tskms_!.pdf.

13. Khamaganova IV, Akhmedov KhB, Tarabrina NP, Khromova SS, Mezentseva MV, Kovalchuk LV et al. Effect of combined therapy using complex of natural cytokines and antimicrobial peptides in urogenital infections caused by Chlamydia and Mycoplasma. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii. 2011;88(1):90–93. (In Russ.) Available at: https://elibrary.ru/qbbzwt.

14. Gromovа O.A., Torshin I.Yu. Chemoinformatic study of spiramycin in comparison with other antibiotics. Farmakoekonomika. Modern Pharmacoeconomics and Pharmacoepidemiology. 2025;18(1):80–94. (In Russ.) https://doi.org/10.17749/2070-4909/farmakoekonomika.2025.296.

15. Redgrove KA, McLaughlin EA. The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword. Front Immunol. 2014;5:534. https://doi.org/10.3389/fimmu.2014.00534.

16. Qiu Y, Mao S, Li X, Chen Y, Chen W, Wen Y, Liu P. Chinese advances in understanding and managing genitourinary tract infections caused by Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma urealyticum. Arch Microbiol. 2024;207(1):5. https://doi.org/10.1007/s00203-024-04204-z.

17. Gómez Rufo D, García Sánchez E, García Sánchez JE, García Moro M. Clinical implications of the genus Mycoplasma. Rev Esp Quimioter. 2021;34(3):169–184. (In Spanish) https://doi.org/10.37201/req/014.2021.

18. Copete A, Herrera M, Suarez-Ariza C, Gitau Z, Arango-Uribe M, Keynan R et al. Mycoplasma genitalium Infections and Associated Antimicrobial Resistance in Canada, 1980–2023. Trop Med Infect Dis. 2025;10(5):139. https://doi.org/10.3390/tropicalmed10050139.

19. Bachmann LH, Manhart LE, Martin DH, Seña AC, Dimitrakoff J, Jensen JS, Gaydos CA. Advances in the Understanding and Treatment of Male Urethritis. Clin Infect Dis. 2015;61(Suppl. 8):S763–S769. https://doi.org/10.1093/cid/civ755.

20. Taylor-Robinson D, Jensen JS. Mycoplasma genitalium: from Chrysalis to multicolored butterfly. Clin Microbiol Rev. 2011;24(3):498–514. https://doi.org/10.1128/CMR.00006-11.

21. Jensen JS, Cusini M, Gomberg M, Moi H, Wilson J, Unemo M. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2022;36(5):641–650. https://doi.org/10.1111/jdv.17972.

22. Gnanadurai R, Fifer H. Mycoplasma genitalium: A Review. Microbiology. 2020;166(1):21–29. https://doi.org/10.1099/mic.0.000830.

23. Jensen JS, Bradshaw C. Management of Mycoplasma genitalium infections – can we hit a moving target? BMC Infect Dis. 2015;15:343. https://doi.org/10.1186/s12879-015-1041-6.

24. Baumann L, Cina M, Egli-Gany D, Goutaki M, Halbeisen FS, Lohrer GR et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect. 2018;94(4):255–262. https://doi.org/10.1136/sextrans-2017-053384.

25. Sadoghi B, Kränke B, Komericki P, Hutterer G. Sexually transmitted pathogens causing urethritis: A mini-review and proposal of a clinically based diagnostic and therapeutic algorithm. Front Med. 2022;9:931765. https://doi.org/10.3389/fmed.2022.931765.

26. Busolo F, Camposampiero D, Bordignon G, Bertollo G. Detection of Mycoplasma genitalium and Chlamydia trachomatis DNAs in male patients with urethritis using the polymerase chain reaction. New Microbiol. 1997;20(4):325–332. Available at: https://pubmed.ncbi.nlm.nih.gov/9385602/.

27. Hetem DJ, Kuizenga Wessel S, Bruisten SM, Braam JF, van Rooijen MS, Vergunst CE et al. High prevalence and resistance rates of Mycoplasma genitalium among patients visiting two sexually transmitted infection clinics in the Netherlands. Int J STD AIDS. 2021;32(9):837–844. https://doi.org/10.1177/0956462421999287.

28. Trembizki E, Buckley C, Bletchly C, Nimmo GR, Whiley DM. High levels of macrolide-resistant Mycoplasma genitalium in Queensland, Australia. J Med Microbiol. 2017;66(10):1451–1453. https://doi.org/10.1099/jmm.0.000584.

29. Couldwell DL, Lewis DA. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations. Infect Drug Resist. 2015;8:147–161. https://doi.org/10.2147/IDR.S48813.

30. Papp JR, Schachter J, Gaydos CA, Van Der Pol B. Recommendations for the Laboratory-Based Detection of Chlamydia trachomatis and Neisseria gonorrhoeae – 2014. MMWR Recomm Rep. 2014;63(RR-02):1–19. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6302a1.htm.

31. Shirshova EV. Urethritis in men: diagnosis and treatment. Almanac of Clinical Medicine. 2007;(15):123–127. (In Russ.) Available at: https://elibrary.ru/hzowqf.

32. Yurasov IV, Yurasova ЕА. Antimicrobial therapy in inflammatory diseases of female reproductive organs. Far East Medical Journal. 2013;(2):105–108. (In Russ.) Available at: https://elibrary.ru/rejulx.

33. Horner P, Blee K, O’Mahony C, Muir P, Evans C, Radcliffe K. 2015 UK National Guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2016;27(2):85–96. https://doi.org/10.1177/0956462415586675.

34. Manhart LE, Gillespie CW, Lowens MS, Khosropour CM, Colombara DV, Golden MR et al. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin Infect Dis. 2013;56(7):934–942. https://doi.org/10.1093/cid/cis1022.

35. Renaudin H, Tully JG, Bebear C. In vitro susceptibilities of Mycoplasma genitalium to antibiotics. Antimicrob Agents Chemother. 1992;36(4):870–872. https://doi.org/10.1128/AAC.36.4.870.

36. Lanjouw E, Ossewaarde JM, Stary A, Boag F, van der Meijden WI. 2010 European guideline for the management of Chlamydia trachomatis infections. Int J STD AIDS. 2010;21(11):729–737. https://doi.org/10.1258/ijsa.2010.010302.

37. Schwebke JR, Rompalo A, Taylor S, Seña AC, Martin DH, Lopez LM et al. Reevaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens – a randomized clinical trial. Clin Infect Dis. 2011;52(2):163–170. https://doi.org/10.1093/cid/ciq074.

38. Horner PJ, Blee K, Falk L, van der Meijden W, Moi H. 2016 European guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2016;27(11):928–937. https://doi.org/10.1177/0956462416648585.

39. Andersen B, van Valkengoed I, Sokolowski I, Møller JK, Østergaard L, Olesen F. Impact of intensified testing for urogenital Chlamydia trachomatis infections: a randomised study with 9-year follow-up. Sex Transm Infect. 2011;87(2):156–161. https://doi.org/10.1136/sti.2010.042192.

40. Street E, Joyce A, Wilson J. BASHH UK guideline for the management of epididymo-orchitis, 2010. Int J STD AIDS. 2011;22(7):361–365. https://doi.org/10.1258/ijsa.2011.011023.

41. Перепанова ТС, Козлов РС, Руднов ВА, Синякова ЛА. Антимикробная терапия и профилактика инфекций почек, мочевыводящих путей и мужских половых органов: федеральные клинические рекомендации. М.: Прима-принт; 2017. 72 с. Режим доступа: https://elibrary.ru/ywvydb.

42. Roy CL, Ferron A, Balcon C, Guiraud J, Bébéar C, de Barbeyrac B, Peuchant O. Impact of Chlamydia trachomatis treatment with azithromycin or doxycycline on Mycoplasma genitalium in women. Int J Infect Dis. 2026;165:108404. https://doi.org/10.1016/j.ijid.2026.108404.

43. Abavisani M, Keikha M. Global analysis on the mutations associated with multidrug-resistant urogenital mycoplasmas and ureaplasmas infection: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob. 2023;22(1):70. https://doi.org/10.1186/s12941-023-00627-6.

44. Perletti G, Marras E, Wagenlehner FM, Magri V. Antimicrobial therapy for chronic bacterial prostatitis. Cochrane Database Syst Rev. 2013;(8):CD009071. https://doi.org/10.1002/14651858.CD009071.pub2.

45. Fan L, Xu J, Zhang N. Photosensitivity of ferrate (VI) in tetracycline degradation: role of solar irradiation and reactive species. Environ Technol. 2026;47(12):1991–1998. https://doi.org/10.1080/09593330.2026.2648630.

46. Hile GA, Coit P, Xu B, Victory AM, Gharaee-Kermani M, Estadt SN et al. Regulation of Photosensitivity by the Hippo Pathway in Lupus Skin. Arthritis Rheumatol. 2023;75(7):1216–1228. https://doi.org/10.1002/art.42460.

47. Falk L, Enger M, Jensen JS. Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women. J Antimicrob Chemother. 2015;70(11):3134–3140. https://doi.org/10.1093/jac/dkv246.

48. Llaca-Díaz J, Casillas-Vega N. Antimicrobial resistance in Mycoplasma genitalium and Mycoplasma hominis: a systematic review in urology. Arch Ital Urol Androl. 2026;98(1):14694. https://doi.org/10.4081/aiua.2026.14694.

49. Arsic B, Barber J, Čikoš A, Mladenovic M, Stankovic N, Novak P. 16-membered macrolide antibiotics: a review. Int J Antimicrob Agents. 2018;51(3):283–298. https://doi.org/10.1016/j.ijantimicag.2017.05.020.

50. Guschin A, Ryzhikh P, Rumyantseva T, Gomberg M, Unemo M. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin. BMC Infect Dis. 2015;15:40. https://doi.org/10.1186/s12879-015-0781-7.

51. Páez-Canro C, Alzate JP, González LM, Rubio-Romero JA, Lethaby A, Gaitán HG. Antibiotics for treating urogenital Сhlamydia trachomatis infection in men and non-pregnant women. Cochrane Database Syst Rev. 2019;(1):CD010871. https://doi.org/10.1002/14651858.CD010871.pub2.

52. Koumaki V, Chasiakou A, Kantzanou M, Tsakris A, Baka S. Antimicrobial resistance of genital mycoplasmas recovered from nonpregnant women in Greece: trends over the last 15 years. Future Microbiol. 2024;19(10):867–875. https://doi.org/10.2217/fmb-2023-0238.

53. Kokkayil P, Dhawan B. Ureaplasma: current perspectives. Indian J Med Microbiol. 2015;33(2):205–214. https://doi.org/10.4103/0255-0857.154850.

54. Jenks JD. Let’s not forget about Mycoplasma genitalium. Sex Health. 2025;22(6):SH25174. https://doi.org/10.1071/SH25174.

55. Ohkawa M, Yamaguchi K, Tokunaga S, Nakashima T, Shoda R. Antimicrobial treatment for chronic prostatitis as a means of defining the role of Ureaplasma urealyticum. Urol Int. 1993;51(3):129–132. https://doi.org/10.1159/000282530.

56. Gill BC, Shoskes DA. Bacterial prostatitis. Curr Opin Infect Dis. 2016;29(1):86–91. https://doi.org/10.1097/QCO.0000000000000222.

57. Naber KG, Weidner W. Prostatitits, Epididymitis and Orchitis. In: Armstrong D, Cohen, J (eds.). Infectious Diseases. London: Mosby; 1999, pp. 58.1–58.6.

58. Badalyan RR, Fanarjyan SV, Aghajanyan IG. Chlamydial and ureaplasmal infections in patients with nonbacterial chronic prostatitis. Andrologia. 2003;35(5):263–265. https://doi.org/10.1046/j.1439-0272.2003.00582.x.

59. Zheng LQ, Wang QY. Prevalence and Antimicrobial Susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in Female Outpatients, 2017–2021. Clin Lab. 2023;69(5). https://doi.org/10.7754/Clin.Lab.2022.220912.

60. Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and mycoplasma genitalium. Nat Rev Urol. 2017;14(3):139–152. https://doi.org/10.1038/nrurol.2016.268.

61. Street EJ, Justice ED, Kopa Z, Portman MD, Ross JD, Skerlev M et al. The 2016 European guideline on the management of epididymo-orchitis. Int J STD AIDS. 2017;28(8):744–749. https://doi.org/10.1177/0956462417699356.

62. Rodrigues R, Marques L, Vieira-Baptista P, Sousa C, Vale N. Therapeutic Options for Chlamydia trachomatis Infection: Present and Future. Antibiotics. 2022;11(11):1634. https://doi.org/10.3390/antibiotics11111634.

63. Hussen NHA, Qadir SH, Rahman HS, Hamalaw YY, Kareem PSS, Hamza BA. Long-term toxicity of fluoroquinolones: a comprehensive review. Drug Chem Toxicol. 2024;47(5):795–806. https://doi.org/10.1080/01480545.2023.2240036.

64. Kohlhoff SA, Hammerschlag MR. Treatment of chlamydial infections: 2014 update. Expert Opin Pharmacother. 2015;16(2):205–212. https://doi.org/10.1517/14656566.2015.999041.

65. Demoly P, Benahmed S, Valembois M, Sahla H, Messaad D, Godard P et al. Allergy to macrolide antibiotics. Review of the literature. Presse Med. 2000;29(6):321–326. (In French) Available at: https://pubmed.ncbi.nlm.nih.gov/10719452/.

66. Fofanova IYu, Prilepskaya VN. Treatment options for urogenital mycoplasma infection during pregnancy. Trudnyi Pacient. 2009;7(12):17–23. (In Russ.) Available at: https://elibrary.ru/ogairj.

67. Chua TP, Vodstrcil LA, Murray GL, Plummer EL, Jensen JS, Unemo M et al. Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated systematic review and meta-analysis. Lancet Microbe. 2025;6(7):101047. https://doi.org/10.1016/j.lanmic.2024.101047.

68. Yasynetskyi M, Banyra O, Nikitin O, Ventskivska I, Kozlov V, Kvach M, Borzhievskyy A. Mixed Sexually Transmitted Infections in Infertile Couples: Empirical Treatment and Influence on Semen Quality. Recent Adv Antiinfect Drug Discov. 2021;16(3):227–236. https://doi.org/10.2174/2772434416666211129105145.

69. Khosropour CM, Manhart LE, Gillespie CW, Lowens MS, Golden MR, Jensen NL et al. Efficacy of standard therapies against Ureaplasma species and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial. Sex Transm Infect. 2015;91(5):308–313. https://doi.org/10.1136/sextrans-2014-051859.

70. Leng X, Zhu R, Ao X, Zhou Y, Zhang K, Hu T et al. Prevalence of Site-Specific Mycoplasma genitalium Infection and Macrolide and FluoroquinoloneAssociated Mutations in Men Who Have Sex with Men in Shenzhen, China. Infect Drug Resist. 2025;18:239–252. https://doi.org/10.2147/IDR.S489403.

71. Shipitsyna E, Khusnutdinova T, Budilovskaya O, Shedko E, Goloveshkina E, Khayrullina G et al. Performance of the first commercial dual resistance assay, AmpliSens Mycoplasma genitalium-ML/FQ-Resist-FL, for detection of potential macrolide and quinolone resistance-associated mutations and prevalence of M. genitalium resistance mutations in St. Petersburg, Russia. Sex Transm Infect. 2023;99(3):191–194. https://doi.org/10.1136/sextrans-2021-055249.

72. Khazan PL, Mnatsakanyan AN, Korabelnikov DI, Ampilogova DM, Petrenko DA. Rehabilitation of patients with vulvovaginal atrophy. Journal of Medical Rehabilitation. 2023;1(1):60–68. (In Russ.) https://doi.org/10.17749/2949-5873/rehabil.2023.5.

73. Bykovshchenko GK, Bykovshchenko AN. Rehabilitation: the result of collaborative efforts among patients, their families, and interdisciplinary rehabilitation team. Journal of Medical Rehabilitation. 2024;2(4):395–401. (In Russ.) https://doi.org/10.17749/2949-5873/rehabil.2024.33.

74. Solokhina TA, Lyadnova EM. Psychological rehabilitation: cognitive behavioral therapy. Journal of Medical Rehabilitation. 2024;2(3):316–321. (In Russ.) https://doi.org/10.17749/2949-5873/rehabil.2024.27.