The potential use of phage therapy in the treatment of exacerbated chronic suppurative otitis media

Introduction. Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear cavities, resulting in per­sistent perforation or retraction of the eardrum of varying size and location. Exacerbation of CSOM is a major public health problem, which is aggravated by the rise of antibiotic resistance of key pathogens (S. aureus, P. aeruginosa). Phage therapy is considered to be a promising alternative or complement to the traditional treatment.

Aim. To evaluate the efficacy and safety of Sextaphage^® (pyobacteriophage polyvalent) as monotherapy and combination ther­apy in exacerbated CSOM.

Materials and methods. An interim data cut was performed of the clinical trial with total 33 patients with exacerbated CSOM included. The patients were divided into 3 groups (11 patients each): 1) standard topical antibacterial therapy (ciprofloxacin); 2) monotherapy by transtympanic delivery of polyvalent pyobacteriophage; 3) combination therapy (pyobacteriophage polyva­lent + ciprofloxacin). Treatment lasted 10 days.

Results and discussion. The clinical resolution of otorrhea was achieved in 90.9% of patients in groups 1 and 3 and in 72.7% of thosed in group 2 by Day 10. The polyvalent pyobacteriophage therapy demonstrated significant clinical and bacteri­olytic efficacy against key pathogens. Combination therapy demonstrated high efficacy (90.9%). Treatment was well tolerated, with no adverse events reported in the study.

Conclusion. The use of polyvalent pyobacteriophage in the integrated treatment of exacerbated chronic otitis media has demonstrated high efficacy and safety, confirming its value in the fight against antibiotic resistance and in improving disease outcomes.

1. Kryukov AI, Garov EV. Current trends in treatment of chronic suppurative otitis media. Doktor. Ru. 2009;(5):21–24. (In Russ.)

2. Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A et al. Burden of disease caused by otitis media: systematic review and global estimates. PLoS ONE. 2012;7(4):e36226. https://doi.org/10.1371/journal.pone.0036226.

3. Garov EV, Khamzalieva RB, Zelenkova VN, Garova EE, Meparishvili AS, Lapenko EG. The medical assistance seeking behaviour of the patients presenting with suppurative chronic otitis media and their treatment in Moscow. Vestnik Oto-Rino-Laringologii. 2018;83(5):26–30. (In Russ.) https://doi.org/10.17116/otorino20188305126.

4. Garov EV, Garova EE. Modern principles of diagnosis and treatment of patients with chronic suppurative otitis media. RMJ. 2012;20(27): 1355–1359. (In Russ.) Available at: https://www.rmj.ru/articles/otorinolaringologiya/Covremennye_principy_diagnostiki_i_lecheniya_pacientov_s_hronicheskim_gnoynym_srednim_otitom/.

5. Roland PS. Chronic suppurative otitis media: a clinical overview. Ear Nose Throat J. 2002;81(8 Suppl. 1):8–10. Available at: https://pubmed.ncbi.nlm.nih.gov/12199189/.

6. Kryukov AI, I Ivoylov AY, Garov EV, Pakina VR, Yanovskiy VV. Effect of microbial flora on the course of chronic suppurative otitis media. Meditsinskiy Sovet. 2014;(3):21–23. (In Russ.) Available at: https://www.med-sovet.pro/jour/article/view/521.

7. Гаров ЕВ, Диаб ХМ, Карнеева ОВ, Юнусов АС, Аникин ИА, Завалий МА и др. Хронический средний отит: клинические рекомендации. М.; 2024. 55 с. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/698_2.

8. Abdulkerimov KhT, Shakhov AV, Ryazantsev SV. The role and place of bacteriophages in modern otorhinolaryngology. Meditsinskiy Sovet. 2019;(8):72–75. (In Russ.) https://doi.org/10.21518/2079-701X-2019-8-72-75

9. Khatun MR, Alam KMF, Naznin M, Salam MA. Microbiology of Chronic Suppurative Otitis Media: An update from a Tertiary Care Hospital in Bangladesh. Pak J Med Sci. 2021;37(3):821–826. https://doi.org/10.12669/pjms.37.3.3942.

10. Yorgancılar E, Yildirim M, Gun R, Bakir S, Tekin R, Gocmez C et al. Complications of chronic suppurative otitis media: a retrospective review. Eur Arch Otorhinolaryngol. 2013;270(1):69–76. https://doi.org/10.1007/s00405-012-1924-8.

11. Maddocks S, Fabijan AP, Ho J, Lin RCY, Ben Zakour NL, Dugan C et al. Bacteriophage Therapy of Ventilator-associated Pneumonia and Empyema Caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2019;200(9):1179-1181. https://doi.org/10.1164/rccm.201904-0839LE.

12. Mapes AC, Trautner BW, Liao KS, Ramig RF. Development of expanded host range phage active on biofilms of multi-drug resistant Pseudomonas aeruginosa. Bacteriophage.2016;6(1):e1096995. https://doi.org/10.1080/21597081.2015.1096995.

13. Gupta A, Schiel V, Bhattacharya R, Eftekharian K, Xia A, Santa Maria PL. Chemokine Receptor CCR2 Is Protective toward Outer Hair Cells in Chronic Suppurative Otitis Media. Immunohorizons. 2024;8(9):688–694. https://doi.org/10.4049/immunohorizons.2400064.

14. Liu K, Wang C, Zhou X, Guo X, Yang Y, Liu W et al. Bacteriophage therapy for drug-resistant Staphylococcus aureus infections. Front Cell Infect Microbiol. 2024;14:1336821. https://doi.org/10.3389/fcimb.2024.1336821.

15. Ikuta KS, Swetschinski LR, Robles Aguilar G, Sharara F, Mestrovic T, Gray AP et al. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400(10369):2221–2248. https://doi.org/10.1016/S0140-6736(22)02185-7.

16. Babaev SYu, Novozhilov AA, Abubakirov TE, Mitrofanova NN, Kozarenko EA, Shakhov AV. Microbiota of the tympanic cavity in patients with chronic suppurative otitis media. Rossiiskaya Otorinolaringologiya. 2019;18(3):22–26. (In Russ.) Available at: https://entru.org/files/preview/2019/03/article/j_rus_LOR_3_2019-22-26.pdf

17. Zalewska-Piątek, B. Phage Therapy—Challenges, Opportunities and Future Prospects. Pharmaceuticals. 2023;16:1638. https://doi.org/10.3390/ph16121638.

18. Dedrick RM, Guerrero-Bustamante CA, Garlena RA, Russell DA, Ford K, Harris K et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med. 2019;25(5):730–733. https://doi.org/10.1038/s41591-019-0437-z.

19. Artemyeva ES, Budkovaya MA, Ryazantsev SV. The possibility of using bacteriophages in otolaryngology. Meditsinskiy Sovet. 2018;(20):24–28. (In Russ.) https://doi.org/10.21518/2079-701X-2018-20-24-28.

20. Preobrazhensky NA, Goldman II, Lipkin AI. The problem of conservative treatment of patients with chronic otitis media. Vestnik Oto-Rino-Laringologii. 1982;(2):18–20. (In Russ.)

21. Volosevich LL, Krivokhatskaya LD, Chemerkin AS. The effectiveness of the use of therapeutic bacteriophages in patients with chronic purulent mesotympanitis. Journal of Ear, Nasal and Throat Diseases. 1985;(3):55–59. (In Russ.)

22. Wright A, Hawkins CH, Anggård EE, Harper DR. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol. 2009;34(4):349–357. https://doi.org/10.1111/j.1749-4486.2009.01973.x.

23. Talibova JKh, Novruzova MS, Bayramova RS, Aliyeva KhM. Use of staphylococcal bacteriophage in the treatment of chronic otitis. Meditsinskie Novosti. 2020;(5):61–63. (In Russ.) Available at: https://cyberleninka.ru/article/n/ispolzovanie-stafilokokkovogo-bakteriofaga-pri-lecheniihronicheskogo-otita.

24. Casazza J, Tan D, Newcomer M, Sakano H, Isaacson B, Hunter JB. Bacteriophage Therapy for Chronic Mastoiditis. Otol Neurotol. 2025;46(4):e117–e119. https://doi.org/10.1097/MAO.0000000000004417.

25. Kurabi A, Sereno E, Ryan AF. Peptides rapidly transport antibiotic across the intact tympanic membrane to treat a middle ear infection. Drug Deliv. 2025;32(1):2463427. https://doi.org/10.1080/10717544.2025.2463427.

26. Kurabi A, Pak KK, Bernhardt M, Baird A, Ryan AF. Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear. Sci Rep. 2016;6:22663. https://doi.org/10.1038/srep22663.