Maltsev S.V. — MD, Professor, Honored Researcher of the Russian Federation and the Republic of Tatarstan, Corresponding Member of the Academy of Sciences of the Republic of Tatarstan, Professor of the Department of Pediatrics named after Acad. G.N. Speransky of RMACPE MOH Russia (Moscow), Chief Editor of the scientific and practical journal for postgraduate education of doctors «Practical Medicine»

 The article presents modern data on urinary system infections and the role of micro- and macroorganisms in the development of diseases. The author outlines the causes and clinical signs of antibiotic resistance, as well as the role of individual pathogens that determine the nature of the course, progression and degree of kidney damage. The groups of patients who are particularly difficult for therapy are singled out. Traditionally, a combination of antibiotics has been used to treat multidrug-resistant infections. Currently, a number of new antibiotics and their combinations are being developed. It has been noted that effective drugs directed against each specific pathogen must be used to treat urinary infections. The article presents strategies implemented to combat microbial drug resistance, as well as promising agents with antimicrobial activity against uropathogens (bacteriophages, vaccines, antimicrobial peptides, dendrimers, nanomaterials and alternative medicine agents).

Key words: urinary system infections, antibiotics, antibiotic resistance, causes, treatment prospects.

REFERENCES

1. Moore S. Recent Research into Urinary Tract Infections (UTIs). News-Medical, 2022.
2. Shikunova Ya.V., Gudkov A.V., Boshchenko V.S. et al. Etiology and pathogenesis of acute pyelonephritis in children. Eksperimental’naya i klinicheskaya urologiya, 2021, vol. 14 (1), pp. 135–139 (in Russ.).
3. Editorial: Out of sync: antimicrobial drug development for children. The Lancet Child & Adolescent Health, 2024, vol. 8 (8), p. 545.
4. Ambite I., Butler D., Wan MLY. et al. Molecular determinants of disease severity in urinary tract infection. Nat. Rev. Urol, 2021, vol. 18 (8), pp. 468–486.
5. Wagenlehner F.M.E., Bjerklund Johansen T.E., Cai T. et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat. Rev. Urol, 2020, vol. 17 (10), pp. 586–600.
6. Montini G., Tullus K., Hewitt I. Febrile urinary tract infections in children. N. Engl. J. Med, 2011, vol. 365 (3), pp. 239–250.
7. Buettcher M., Trueck J., Niederer-Loher A. et al. Swiss consensus recommendations on urinary tract infections in children. Eur. J. Pediatr, 2021, vol. 180 (3), pp. 663–674.
8. Hughes K., Cannings-John R., Jones H. et al. Long-term consequences of urinary tract infection in childhood: an electronic population-based cohort study in Welsh primary and secondary care. Brit. J. General Pract, 2024, vol. 74 (743), pp. e371–e378.
9. Neugent M.L., Hulyalkar N.V., Nguyen V.H. et al. Advances in understanding the human urinary microbiome and its potential role in urinary tract infection. mBio, 2020, vol. 11(2), pp. 00218–20.
10. Roth R.S., Liden M., Huttner A. The urobiome in men and women: a clinical review. Clin. Microbiol. Infect, 2023, vol. 29 (10), pp. 1242–1248.
11. Shoemaker R., Kim J. Urobiome: An outlook on the metagenome of urological diseases. Investig. Clin. Urol, 2021, vol. 62 (6), pp. 611–622.
12. Shaker M., Zaki A., Asser S.L. et al. Trends and predictors of antimicrobial resistance among patients with urinary tract infections at a tertiary hospital facility in Alexandria, Egypt: a retrospective record-based classification and regression tree analysis. BMC Infect. Dis, 2024, vol. 24, p. 246.
13. Daudova A.D., Demina Yu.Z., Genatullina G.N. et al. Antibiotic resistance. The challenge of our time. Antibiotiki i Khimioterapiya, 2023, no. 68 (3–4), pp. 66–75 (in Russ.).
14. WHO releases report on state of development of antibacterials. News release. Geneva, Switzerland, 14 June 2024.
15. Murray C.J.L. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis Antimicrobial Resistance Collaborators. Lancet, 2022, vol. 399 (10325), pp. 629–655.
16. IFPMA delivered a statement at the second meeting of the Ad Hoc Open-ended Working Group on Benefit-sharing for the use of Digital Sequence Information (DSI) in Montreal, Canada, 12 August 2024.
17. Addressing antibiotic resistance: an interview with Professor Otto Cars. Uppsala University, Sweden. News Medical Life Science, Feb 3 2014.
18. Yakovlev S.V., Gadzhieva Z.K., Suvorova M.P. Antimicrobial activity of nitrofurans (nitrofurantoin, furazidin and furazidin potassium salt) against uropathogenic Escherichia coli isolated from patients with lower urinary tract infections. Urologiya, 2024, no. 3, pp. 113–120 (in Russ.).
19. Bader M.S., Loeb M., Brooks A.A. An update on the management of urinary tract infections in the era of antimicrobial resistance. Postgraduate Medicine, 2016, vol. 129 (2), pp. 242–258.
20. Mulani M.S., Kamble E.E., Kumkar S.N. et al. Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: a review. Fron. Microbiol, 2019, vol. 10, p. 539.
21. Mahmood H.Y., Jamshidi S., Sutton J.M., Rahman K.M. Current advances in developing inhibitors of bacterial multidrug efflux pumps. Curr. Med. Chem, 2016, vol. 23 (10), pp. 1062–1081.
22. Álvarez-Ainza M.L., Alejandro P. et al. Antibiotic resistance of ESKAPE group-microorganisms in health institutions from Hermosillo and Ciudad Obregón? Sonora, México. Front. Cell. Infect. Microbiol, 2024, vol. 14.
23. Zaffanello M., Malerba G. Genetic risk for recurrent urinary tract infections in humans: a systematic review. J. Biomed. Biotechnol, 2010, vol. 2010, 321082.
24. Collignon P.J., McEwen S.A. One health-its importance in helping to better control antimicrobial resistance. Tropical Med. Infect. Dis, 2019, vol. 4 (1), p. 22.
25. Ma Y.X., Wang C.Y., Li Y.Y. et al. Considerations and caveats in combating ESKAPE pathogens against nosocomial infections. Adv. Sci, 2020, vol. 7 (1), 1901872.
26. Wegener H.C. Improving food safety through a One Health approach. Washington: National Academy of Sciences. Antibiotic resistance — Linking human and animal health, 2012. Pp. 331–349.
27. Melander R.J., Mattingly A.E., Nemeth A.M., Melander C. Overcoming intrinsic resistance in gram-negative bacteria using small molecule adjuvants. Bioorg. Med. Chem. Lett, 2023, vol. 80, 129113.
28. Gonzalez-Villarreal J.A., Gonzalez-Lozano K.J., Arechiga-Carvajal et al. Molecular mechanisms of multidrug resistance in clinically relevant enteropathogenic bacteria (Review). Exp. Ther. Med, 2022, vol. 24, p. 753.
29. Letao B., Haidong S., Yi-Dong et al. Combating antimicrobial resistance: the silent war. Front. Pharmacol, 2024, vol. 15.
30. Breijyeh Z., Jubeh B., Karaman R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules, 2020, vol. 25, p. 1340.
31. Reygaert W.C. An overview of the antimicrobial resistance mechanisms of bacteria.. AIMS Microbiol, 2018, vol. 4, pp. 482–501.
32. Finding ways to fight antimicrobial resistance: present, future, and perspectives. Antibiotics, 2024, vol. 13 (2), p. 171.
33. Fernandez L., Hancock R.E. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin. Microbiol. Rev, 2012, vol. 25, pp. 661–681.
34. Adhikari M., Roychowdhury A., Tiwary B.K. Quorum quenching enzymes: a potent alternative to conventional antibiotics. In: Saha T., Adhikari M., Tiwary B.K. (eds) Alternatives to Antibiotics. Springer, Singapore, 2022. DOI: 10.1007/978-981-19-1854-4_3
35. Dutt Y., Dhiman R., Singh T. et al. The association between biofilm formation and antimicrobial resistance with possible ingenious bio-remedial approaches. Antibiot. (Basel), 2022, vol. 11, p. 930.
36. Mukhin N.A. Decreased glomerular filtration rate — a general population marker of unfavorable prognosis. Terapevticheskiy arkhiv, 2007, vol. 79, no. 6, pp. 1–10 (in Russ.).
37. Salim S.A., Mohan M.S., Forgia N., Busi S. Medical Importance of ESKAPE Pathogens. In: Busi, S., Prasad, R. (eds) ESKAPE Pathogens. Springer, Singapore, 2024.
38. Antibiotic resistance of pathogens causing community-acquired urinary tract infections in Russia: results of the multicenter study “DARMIS-2018” and the research group “DARMIS-2018”. KMAKh, 2019, no. 21 (2), pp. 134–146 (in Russ.).
39. Shaker M., Zaki A., Asser S.L., Sayed I.E. Trends and predictors of antimicrobial resistance among patients with urinary tract infections at a tertiary hospital facility in Alexandria, Egypt: a retrospective record-based classification and regression tree analysis. BMC Infect. Dis, 2024, vol. 24 (1), p. 246.
40. Chou A., Welch E., Hunter A., Trautner B.W. Antimicrobial treatment options for difficult-to-treat resistant gram-negative bacteria causing cystitis, pyelonephritis, and prostatitis: a narrative review. Drugs, 2022, vol. 82 (4), pp. 407–438.
41. Tilahun M., Kassa Y., Gedefie A., Ashagire M. Emerging carbapenem-resistant enterobacteriaceae infection, its epidemiology and novel treatment options: a revie. Infect. Drug Resist, 2021, vol. 14, pp. 4363–4374.
42. Tilak Saha, Manab Deb Adhikari, Bipransh Kumar Tiwary (Ed.). Alternatives to antibiotics recent trends and future prospects. Springer. 2022. 571 p.
43. Turgay Akgül, Tolga Karakan. The role of probiotics in women with recurrent urinary tract infections. Turk. J. Urol, 2018, vol. 44 (5), pp. 377–383.
44. Kishor Tewary, Hassib Narchi. Recurrent urinary tract infections in children: Preventive interventions other than prophylactic antibiotics. World J. Methodol, 2015, vol. 5 (2), pp. 13–19.
45. Kenneally C., Murphy C.P., Sleator R.D., Culligan E.P. Turbidimetric bioassays: A solution to antimicrobial activity detection in asymptomatic bacteriuria isolates against uropathogenic Escherichia coli. Microbiol. Open, 2024, vol. 13 (3), p. e1411.
46. Zalewska-Piątek B., Piątek R. Phage therapy as a novel strategy in the treatment of urinary tract infections caused by E. coli. Antibiotics (Basel), 2020, vol. 9 (6), p. 304.
47. Rosini R., Nicchi S., Pizza M., Rappuoli R. Vaccines against antimicrobial resistance. Front. Immunol, 2020, vol. 11, p. 1048.
48. Jingshu Yang Y.Y., Yang Y. Regulatory lessons from China’s COVID-19 vaccines development and approval policies. Acta Mater. Medica, 2022, vol. 1, pp. 96–105.
49. Loubet P., Ranfaing J., Dinh A. Alternative therapeutic options to antibiotics for the treatment of urinary tract infections. Front. Microbiol, 2020, vol. 11, p. 3.
50. Gasanov V., Vorotelyak E., Vasiliev A. Expression of the antimicrobial peptide SE-33-A2P, a modified analog of cathelicidin, and an analysis of its propertiesby. Antibiotics, 2024, vol. 13 (2), p. 190.
51. Glebov A. The winner of superbugs. Kommersant, 07.11.2022 (in Russ.).
52. Chis A.A., Dobrea C., Morgovan C. et al. Applications and limitations of dendrimers in biomedicine. Molecules, 2020, vol. 25, p. 17.
53. Damyanova T., Dimitrova P.D., Borisova D. An overview of biofilm-associated infections and the role of phytochemicals and nanomaterials in their control and prevention. Pharmaceutics, 2024, vol. 16 (2), p. 162.
54. Straniero V. Finding ways to fight antimicrobial resistance: present, future, and perspectives. Antibiotics, 2024, vol. 13 (2), p. 171.
55. Geddes L. Scientists hail new antibiotic that can kill drug-resistant bacteria. The Guardian, 3 Jan. 2024.
56. Hu P., Li S., Niu Z. Prediction of synergistic drug combinations by learning from deep representations of multiple networks. Stud. Health Technol, 2019, inf. 264, pp. 1482–1483.
57. Kranz J., Helbig S., Mandraka F. et al. The revival of old antibiotics for treatment of uncomplicated urinary tract infections in the era of antibiotic stewardship. Curr. Opin. Urol, 2017, vol. 27 (2), pp. 127–132.
58. Al-Amin M.Y., Lahiry A., Ferdous R., Hasan M.K., Kader M.A., Alam A.K. et al. Stephania japonica ameliorates scopolamine-induced memory impairment in mice through inhibition of acetylcholinesterase and oxidative stress. Adv. Pharmacol. Pharm. Sci, 2022, 8305271.
59. Kundo N.K., Manik M.I.N., Biswas K. et al. Identification of polyphenolics from loranthus globosus as potential inhibitors of cholinesterase and oxidative stress for Alzheimer’s disease treatment. Biomed. Res. Int., 2021.
60. Sukumaran S., Nadarajan S. Marine peptides and their bioactive potentials: new horizon for biotherapeutics. In: Haridas M., Abdulhameed S., Francis D., Kumar S.S. (eds.) Drugs from Nature: Targets, Assay Systems and Leads. Springer, Singapore, 2024. Pp. 153–178.
61. Muller A.E., Verhaegh E.M., Harbarth S. et al. Nitrofurantoin’s efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials. Clin. Microbiol. Inf., 2017, vol. 23, pp. 355–362.
62. Perepanova T.S. Nitrofurans in urological practice: are they all the same and why are we returning to them today? Eksperimental’naya i klinicheskaya urologiya, 2018, no. 3, pp. 91–100 (in Russ.).
63. Sihra N., Goodman A., Zakri R. et al. Nonantibiotic prevention and management of recurrent urinary tract infection. Nat. Rev Urol, 2018, vol. 15, pp. 750–776.
64. Christopher J.L., Murray K., Shunji I., Fablina Sh. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet, 2022. DOI: 10.1016/S0140-6736(21)02724-0
65. Antimicrobial resistance collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet, 2022, vol. 400 (10358), p. 1102.
66. New Approaches to Combat Antibiotic-resistant Bacteria. 2nd ed. Ascona, Switzerland, 2024 June 13.