Integration of national policy, local microbiological monitoring and phage therapy in counteracting antimicrobial resistance

Antimicrobial resistance (AMR) is a major medical and social threat because it reduces the clinical effectiveness of antimicrobial therapy, increases the risk of poor infectious disease outcomes and requires coordinated action at the levels of health policy, laboratory services and clinical practice. The aim of this review was to consider AMR control as an integrated system combining national policy, local microbiological monitoring, antimicrobial stewardship and emerging anti-infective technologies, including phage therapy. A narrative analytical review of international and Russian guidance documents, methodological papers and scientific publications addressing AMR surveillance, local susceptibility data, cumulative antibiograms, clinically oriented monitoring and bacteriophage-based treatment of infections caused by resistant Gram-negative pathogens was performed. The clinical value of local monitoring is determined not only by the volume of laboratory data but also by the quality of metadata, separation of diagnostic and screening isolates, deduplication of repeated cultures, expert assessment of results and direct linkage between reports and local empirical treatment protocols. Phage therapy is considered a promising personalised and adjunctive approach for infections caused by Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, particularly when standard antibacterial therapy has limited effectiveness. However, its broader implementation requires standardisation of phage susceptibility testing, development of phage banks, regulatory solutions, quality control of preparations and assessment of clinical efficacy in controlled studies. Integration of surveillance, clinical microbiology, digital platforms, antimicrobial stewardship and phage technologies may be considered a promising model for AMR containment in routine clinical practice.

1. World Health Organization. Global action plan on antimicrobial resistance. 2016. Available at: www.who.int/publications/i/item/9789241509763. Accessed April 11, 2025.

2. Давыдов Д.С. Национальная стратегия Российской Федерации по предупреждению распространения устойчивости микроорганизмов и вредных организмов растений к лекарственным препаратам, химическим и биологическим средствам. БИОпрепараты. Профилактика, диагностика, лечение. 2018; 18 (1): 52–56. [Davydov DS. Natsionalʹnaya strategiya Rossijskoj Federatsii po preduprezhdeniyu rasprostraneniya ustojchivosti mikroorganizmov i vrednykh organizmov rastenij k lekarstvennym preparatam, khimicheskim i biologicheskim sredstvam. BIOpreparaty. Profilaktika, diagnostika, lechenie. 2018; 18 (1): 52–56. (In Russ.)].

3. OECD-WHO. Addressing the burden of infections and antimicrobial resistance associated with health care. 2025. Available at: www.oecd.org/content/dam/oecd/en/topics/policy-sub-issues/antimicrobial-resistance-and-pandemics/addressing-burden-of-infections-and-amr-associated-with-health-care.pdf. Accessed April 11, 2025.

4. Balasubramanian R., Van Boeckel T.P., Carmeli Y., Cosgrove S., Laxminarayan R. Global incidence in hospital-associated infections resistant to antibiotics: an analysis of point prevalence surveys from 99 countries. PLoS Med. 2023; 20 (6): e1004178. doi: 10.1371/journal.pmed.1004178.

5. Miller W.R., Arias C.A. ESKAPE pathogens: Antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nat Rev Microbiol. 2024; 22: 598–616. doi: 10.1038/s41579-024-01054-w.

6. Loc-Carrillo C., Abedon S.T. Pros and cons of phage therapy. Bacteriophage. 2011; 1: 111–114. doi: 10.4161/bact.1.2.14590.

7. World Health Organization. GLASS manual for antimicrobial resistance surveillance in common bacteria causing human infection. Published online, 2023. Available at: www.who.int/publications/i/item/9789240076600. Accessed April 11, 2025.

8. Кузьменков А.Ю., Виноградова А.Г., Трушин И.В., Эйдельштейн М.В., Авраменко А.А., Дехнич А.В. и др. AMRmap - система мониторинга антибиотикорезистентности в России. Клиническая микробиология и антимикробная химиотерапия. 2021; 23 (2):198–204. [Kuzʹmenkov AYu, Vinogradova AG, Trushin IV, Ejdelʹshtejn MV, Avramenko AA, Dekhnich AV, et al. AMRmap - sistema monitoringa antibiotikorezistentnosti v Rossii. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2021; 23 (2):198–204. (In Russ.)]. doi: https://doi.org/10.36488/cmac.2021.2.198-204.

9. Tacconelli E., Sifakis F., Harbarth S., Schrijver R., Mourik M., Voss A., et al. Surveillance for control of antimicrobial resistance. Lancet Infect Dis. 2018; 18 (3): e99–e106. doi: 10.1016/S1473-3099(17)30485-1.

10. Barlam T.F., Cosgrove S.E., Abbo L.M., MacDougall C., Schuetz A., Septimus E., et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016; 62 (10): e51–e77. doi: 10.1093/cid/ciw118.

11. Simner P.J., Hindler J.A., Bhowmick T., Das S., Johnson J., Lubers B., et al. What's new in antibiograms? Updating CLSI M39 guidance with current trends. J Clin Microbiol. 2022; 60 (10): e0221021. doi: 10.1128/jcm.02210-21.

12. Cornaglia G., Hryniewicz W., Jarlier V., Kahlmeter G., Mittermayer H., Stratchounski L., et al. European recommendations for antimicrobial resistance surveillance. Clin Microbiol Infect. 2004; 10 (4): 349–383. doi: 10.1111/j.1198-743x.2004.00887.x.

13. Авраменко А.А., Бурасова Е.Г., Виноградова А.Г., Гусаров В.Г., Ершова О.Н., Замятин М.Н. и соавт. Мониторинг антибиотикорезистентности с использованием платформы AMRcloud. Практическое руководство. Смоленск: СГМУ; 2021; 160. [Avramenko AA, Burasova EG, Vinogradova AG, Gusarov VG, Ershova ON, Zamyatin MN i soavt. Monitoring antibiotikorezistentnosti s ispolʹzovaniem platformy AMRcloud. Prakticheskoe rukovodstvo. Smolensk: SGMU; 2021; 160. (In Russ.)].

14. Методические рекомендации МР 3.1.0346-24 «Организация и проведение микробиологического мониторинга в медицинских организациях» (утв. Федеральной службой по надзору в сфере защиты прав потребителей и благополучия человека 26 апреля 2024 г.). [Metodicheskie rekomendatsii MR 3.1.0346-24 «Organizatsiya i provedenie mikrobiologicheskogo monitoringa v meditsinskikh organizatsiyakh» (utv. Federalʹnoj sluzhboj po nadzoru v sfere zashchity prav potrebitelej i blagopoluchiya cheloveka 26 aprelya 2024 g.). (In Russ.)]. Available at: www.garant.ru/products/ipo/prime/doc/408994558/. Accessed April 11, 2025.

15. Lim C., Ashley E.A., Hamers R.L., Turner P., Kesteman T., Akech S., et al. Surveillance strategies using routine microbiology for antimicrobial resistance in low- and middle-income countries. Clin Microbiol Infect. 2021; 27 (10): 1391–1399. doi: 10.1016/j.cmi.2021.05.037.

16. Turner P., Ashley E.A., Celhay O.J., Douangnouvong A., Hamers R., Ling C., et al. ACORN: A Clinically-Oriented Antimicrobial Resistance Surveillance Network: a pilot protocol for case based antimicrobial resistance surveillance. Wellcome Open Res. 2020; 5: 13. doi: https://doi.org/10.12688/wellcomeopenres.15681.1.

17. Виноградова А.Г., Кузьменков А.Ю. Организация данных как основа локального мониторинга антибиотикорезистентности. Клиническая микробиология и антимикробная химиотерапия. 2020; 22 (2): 137–141. [Vinogradova AG, Kuzʹmenkov AYu. Organizatsiya dannykh kak osnova lokalʹnogo monitoringa antibiotikorezistentnosti. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2020; 22 (2): 137–141. (In Russ.)]. doi: https://doi.org/10.36488/cmac.2020.2.137-141.

18. Kohlmann R., Gatermann S.G. Analysis and presentation of cumulative antimicrobial susceptibility test data - the influence of different parameters in a routine clinical microbiology laboratory. PLoS One. 2016; 11 (1): e0147965. doi: 10.1371/journal.pone.0147965.

19. Виноградова А.Г., Кузьменков А.Ю., Трушин И.В., Эйдельштейн М.В., Сухорукова М.В., Старостенков А.А. AMRexpert - онлайн-платформа для интерпретации, верификации и валидации результатов определения чувствительности микроорганизмов к антимикробным препаратам. Клиническая микробиология и антимикробная химиотерапия. 2023; 25 (1): 68–76. [Vinogradova AG, Kuzʹmenkov AYu, Trushin IV, Ejdelʹshtejn MV, Sukhorukova MV, Starostenkov AA. AMRexpert - onlajn-platforma dlya interpretatsii, verifikatsii i validatsii rezulʹtatov opredeleniya chuvstvitelʹnosti mikroorganizmov k antimikrobnym preparatam. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2023; 25 (1): 68–76. (In Russ.)]. doi: https://doi.org/10.36488/cmac.2023.1.68-76.

20. Cressman A.M., MacFadden D.R., Verma A.A., Razak F., Daneman N. Empiric antibiotic treatment thresholds for serious bacterial infections: a scenario-based survey study. Clin Infect Dis. 2019; 69 (6): 930–937. doi: 10.1093/cid/ciy1031.

21. Кузьменков А.Ю., Виноградова А.Г., Трушин И.В., Авраменко А.А., Эйдельштейн М.В., Дехнич А.В. и соавт. AMRcloud: новая парадигма мониторинга антибиотикорезистентности. Клиническая микробиология и антимикробная химиотерапия. 2019; 21 (2): 119–124. [Kuzʹmenkov AYu, Vinogradova AG, Trushin IV, Avramenko AA, Ejdelʹshtejn MV, Dekhnich AV i soavt. AMRcloud: novaya paradigma monitoringa antibiotikorezistentnosti. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2019; 21 (2): 119–124. (In Russ.)]. doi: https://doi.org/10.36488/cmac.2019.2.119-124.

22. AMRnote - онлайн-платформа для создания, редактирования и обмена протоколами и алгоритмами терапии. Available at: https://amrnote.net/ru/. Accessed April 13, 2025.

23. Simpao A., Ahumada L., Larru Martinez B., Cardenas A., Metjian T., Sullivan K., et al. Design and implementation of a visual analytics electronic antibiogram within an electronic health record system at a tertiary pediatric hospital. Appl Clin Inform. 2018; 9 (1): 37–45. doi: 10.1055/s-0037-1615787.

24. Яковлев С.В., Брико Н.И., Сидоренко С.В., Проценко Д.Н. Программа СКАТ (Стратегия Контроля Антимикробной Терапии) при оказании стационарной медицинской помощи. 2018; 156. [Yakovlev SV, Briko NI, Sidorenko SV, Protsenko DN. Programma SKAT (Strategiya Kontrolya Antimikrobnoj Terapii) pri okazanii statsionarnoj meditsinskoj pomoshchi. 2018; 156. (In Russ.)].

25. Schooley R.T., Biswas B., Gill J.J., Hernandez-Morales A., Lancaster J., Lessor L., Barr J.J., et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 2017; 61: e00954-17. doi: 10.1128/aac.00954-17.

26. Doub J.B., Shishido A., Srikumaran U., Haskoor J., Tran-Nguyen P., Lee M., et al. Salphage: Salvage bacteriophage therapy for a recalcitrant Klebsiella pneumoniae prosthetic shoulder infection - A case report. Acta Orthop. 2022; 93: 756–759. doi: 10.2340/17453674.2022.4579.

27. Corbellino M., Kieffer N., Kutateladze M., Balarjishvili N., Leshkasheli L., Askilashvili L., et al. Eradication of a multidrug-resistant, carbapenemase-producing Klebsiella pneumoniae isolate following oral and intra-rectal therapy with a custom made, lytic bacteriophage preparation. Clin Infect Dis. 2020; 70: 1998–2001. doi: 10.1093/cid/ciz782.

28. Eskenazi A., Lood C., Wubbolts J., Hites M., Balarjishvili N., Leshkasheli L., Askilashvili L., et al. Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae. Nat Commun. 2022; 13: 302. doi: 10.1038/s41467-021-27656-z.

29. Chen Q., Zhang F., Bai J., Che Q., Xiang L., Zhang Z., Wang Y., et al. Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence. Int J Antimicrob Agents. 2024; 64: 107221. doi: 10.1016/j.ijantimicag.2024.107221.

30. Yang X., Haque A., Matsuzaki S., Matsumoto T., Nakamura S. The efficacy of phage therapy in a murine model of Pseudomonas aeruginosa pneumonia and sepsis. Front Microbiol. 2021; 12: 682255. doi: 10.3389/fmicb.2021.682255.

31. Jeon J., Yong D. Two novel bacteriophages improve survival in Galleria mellonella infection and mouse acute pneumonia models infected with extensively drug-resistant Pseudomonas aeruginosa. Appl Environ Microbiol. 2019; 85: e02900-18. doi: 10.1128/AEM.02900-18.

32. Simner P.J., Cherian J., Suh G.A., Bergman Y., Beisken S., Fackler J., Lee M., et al. Combination of phage therapy and cefiderocol to successfully treat Pseudomonas aeruginosa cranial osteomyelitis. JAC Antimicrob Resist. 2022; 4: dlac046. doi: 10.1093/jacamr/dlac046.

33. Van Nieuwenhuyse B., Van der Linden D., Chatzis O., Lood C., Wagemans J., Lavigne R., Schroven K., et al. Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler. Nat Commun. 2022; 13: 5725. doi: 10.1038/s41467-022-33294-w.

34. Jault P., Leclerc T., Jennes S., Pirnay J.P., Que Y.A., Resch G., Rousseau A.F., et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): A randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis. 2019; 19: 35–45. doi: 10.1016/S1473-3099(18)30482-1.

35. Wright A., Hawkins C.H., Anggard E.E., Harper D.R. 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: 349–357. doi: 10.1111/j.1749-4486.2009.01973.x.

36. Gordillo Altamirano F.L., Kostoulias X., Subedi D., Korneev D., Peleg A.Y., Barr J.J. Phage-antibiotic combination is a superior treatment against Acinetobacter baumannii in a preclinical study. EBioMedicine. 2022; 80: 104045. doi: 10.1016/j.ebiom.2022.104045.

37. Gordillo Altamirano F., Forsyth J.H., Patwa R., Kostoulias X., Trim M., Subedi D., Archer S.K., et al. Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials. Nat Microbiol. 2021; 6: 157–161. doi: 10.1038/s41564-020-00830-7.

38. Rao S., Betancourt-Garcia M., Kare-Opaneye Y.O., Swierczewski B.E., Bennett J.W., Horne B., Fackler J., et al. Critically ill patient with multidrug-resistant acinetobacter baumannii respiratory infection successfully treated with intravenous and nebulized bacteriophage therapy. Antimicrob Agents Chemother. 2022; 66: e0082421. doi: 10.1128/AAC.00824-21.

39. Chegini Z., Khoshbayan A., Taati Moghadam M., Farahani I., Jazireian P., Shariati A. Bacteriophage therapy against Pseudomonas aeruginosa biofilms: A review. Ann Clin Microbiol Antimicrob. 2020; 19: 45. doi: 10.1186/s12941-020-00389-5.

40. Comeau A.M., Tetart F., Trojet S.N., Prere M.F., Krisch H.M. Phage-Antibiotic Synergy (PAS): Beta-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS One. 2007; 2: e799. doi: 10.1371/journal.pone.0000799.

41. Gu Liu C., Green S.I., Min L., Clark J.R., Salazar K.C., Terwilliger A.L., Kaplan H.B., et al. Phage-antibiotic synergy is driven by a unique combination of antibacterial mechanism of action and stoichiometry. mBio. 2020; 11: e01462-20. doi: 10.1128/mBio.01462-20.

42. Dabrowska K. Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review. Med Res Rev. 2019; 39: 2000–2025. doi: 10.1002/med.21572.

43. Daubie V., Chalhoub H., Blasdel B., Dahma H., Merabishvili M., Glonti T., De Vos N., et al. Determination of phage susceptibility as a clinical diagnostic tool: A routine perspective. Front Cell Infect Microbiol. 2022; 12: 1000721. doi: 10.3389/fcimb.2022.1000721.

44. Li P., Guo G., Zheng X., Xu S., Zhou Y., Qin X., Hu Z., et al. Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection. Vet Res. 2024; 55: 59. doi: 10.1186/s13567-024-01311-z.

45. Chen X., Liu M., Zhang P., Xu M., Yuan W., Bian L., Liu Y., Xia J., Leung S.S.Y. Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter baumannii. Front Microbiol. 2022; 13: 845500. doi: 10.3389/fmicb.2022.845500.