Антибиотикорезистентность в неонатологии: Важные вопросы и возможные пути решения
Ключевые слова:
антибиотикорезистентность, неонатальный сепсис, новорожденные, антибактериальная терапия, интенсивная терапия, управление антибиотикамиАннотация
Антибиотикорезистентность в неонатологии остается одной из наиболее серьезных угроз здравоохранению, особенно в отделениях интенсивной терапии новорожденных, где высока доля инфекций, вызванных множественно устойчивыми патогенами. Цель обзора: изучить эпидемиологию антибиотикорезистентных бактериальных возбудителей у новорожденных, проанализировать современные подходы к мониторингу потребления антибиотиков и практикам антимикробной терапии, а также рассмотреть опыт реализации стратегий по сдерживанию антимикробной резистентности в неонатологии в мире и в Республике Казахстан.
Проведен обзор научных публикаций и официальных статистических источников за период с 2015 по 2025 гг., включая международные и отечественные исследования. Особое внимание уделено данным, касающимся динамики резистентности наиболее распространенных неонатальных патогенов, применяемым методикам учета потребления антибиотиков (DOT, LOT, DDD), а также анализу реализации программ управления антимикробной терапией. Выявлено устойчивое распространение патогенов с множественной лекарственной устойчивостью, таких как Klebsiella pneumoniae, E. coli, Enterobacter spp., Acinetobacter baumannii и Staphylococcus epidermidis. В странах с низким и средним уровнем дохода отмечается более высокая частота таких инфекций по сравнению с развитыми странами. В Казахстане реализованы меры по внедрению мониторинга потребления антибиотиков, однако сохраняются проблемы с доступностью микробиологической диагностики, кадровым обеспечением и стандартизацией подходов. Анализ показывает эффективность применения количественных методов учета (DOT, LOT) для оценки антимикробной нагрузки. Международный опыт демонстрирует, что внедрение программ управления антимикробной терапией способствует снижению нецелевого использования антибиотиков и улучшению клинических исходов. В Казахстане требуется дальнейшая систематизация данных, усиление лабораторной поддержки и развитие междисциплинарных команд в рамках программ управления антимикробной терапией. Формирование эффективной стратегии борьбы с антибиотикорезистентностью в неонатологии требует комплексного подхода, включающего эпиднадзор, обучение персонала, микробиологическую поддержку и государственную политику. Казахстану необходимо продолжать развитие национальной системы мониторинга, внедрение современных инструментов анализа и обмен международным опытом.
Библиографические ссылки
1. Licona, G., Ballot, D., & Moon, T. D. (2023). Multidrug-resistant bacterial infections among very low birthweight infants with late-onset sepsis in Johannesburg, South Africa. Open Forum Infectious Diseases, 10(8), ofad362. https://doi.org/10.1093/ofid/ofad362
2. World Health Organization. (2024). Newborn mortality. Website. [Cited 14 Nov 2025]. Available from URL:
https://www.who.int/news-room/fact-sheets/detail/newborn-mortality
3. Harrison, M. L., Dickson, B. F., Sharland, M., & Williams, P. C. M. (2024). Beyond early- and late-onset neonatal sepsis definitions: What are the current causes of neonatal sepsis globally? A systematic review and metaanalysis of the evidence. Pediatric Infectious Disease Journal, 43(12), 1182–1190. https://doi.org/10.1097/INF.0000000000004485
4. Russell, N. J., Stöhr, W., Plakkal, N., & Cook, A. (2023). Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS). PLoS Medicine, 20(6), e1004179. https://doi.org/10.1371/journal.pmed.1004179
5. World Health Organization. (2023). Antimicrobial resistance. Website. [Cited 21 Nov 2025]. Available from URL: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
6. Langford, B. J., Soucy, J. P., Leung, V., So, M., Kwan, A. T. H., & Portnoff, J. S. (2023). Antibiotic resistance associated with the COVID-19 pandemic: A systematic review and meta-analysis. Clinical Microbiology and Infection, 29(3), 302–309. https://doi.org/10.1016/j.cmi.2022.12.006
7. Rizvi, S. G., & Ahammad, S. Z. (2022). COVID-19 and antimicrobial resistance: A cross-study. Science of the Total Environment, 807(Pt 2), 150873. https://doi.org/10.1016/j.scitotenv.2021.150873
8. Yin, Z., Tan, J., & Huang, H. (2024). Trends in the antimicrobial susceptibility among Chinese neonates from 2012 to 2021: A multicenter study. Antimicrobial Resistance & Infection Control, 13, 83. https://doi.org/10.1186/s13756-024-01440-2
9. Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Cox, E. M., Houchens, C. R., Grayson, M. L., Hansen, P., Singh, N., … Magrini, N. (2018). Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, 18(3), 318–327. https://doi.org/10.1016/S1473-3099(17)30753-3
10. Ojeda, A., Akinsuyi, O., McKinley, K. L., Xhumari, J., & Triplett, E. W. (2024). Increased antibiotic resistance in preterm neonates under early antibiotic use. mSphere, 9(10), e0028624. https://doi.org/10.1128/msphere.00286-24
11. Flannery, D. D., Chiotos, K., Gerber, J. S., & Puopolo, K. M. (2022). Neonatal multidrug-resistant gramnegative infection: Epidemiology, mechanisms of resistance, and management. Pediatric Research, 91(2), 380–391. https://doi.org/10.1038/s41390-021-01745-7
12. Dong, Y., & Speer, C. P. (2022). Late-onset neonatal sepsis: Recent developments. Journal of Infectious Diseases and Epidemiology, 8, 281. https://doi.org/10.23937/2474-3658/1510281
13. Duma, N., Aguilera, J. V., Paludo, J., Haddox, C. L., Gonzalez-Velez, M., & Wang, Y. (2021). Immune checkpoint inhibitors for treatment of non-small cell lung cancer with brain metastases. JAMA Network Open, 4(9), e2124938. https://doi.org/10.1001/jamanetworkopen.2021.24938
14. Faix, R. G. (2021). Neonatal sepsis: A continuing challenge. Advances in Neonatal Care, 21(1), 49–60.
https://doi.org/10.1097/ANC.0000000000000769
15. Verroken, A., Bauraing, C., & De Mendonça, R. (2020). Epidemiology and impact of multidrug-resistant bacteria in Belgian neonatal intensive care units. European Journal of Clinical Microbiology & Infectious Diseases, 39(10), 1879–1884.
https://doi.org/10.1007/s10096-020-03921-9
16. Reiss, I. K., de Jong, E., Visser, D. H., Lopriore, E., Krediet, T. G. M., Vermeulen, J. L., van Kaam, A. H., de Boer, M. P., Sloots, C. E. J., Rübsamen-Schaeff, H., Knol, M. J., Hazebroek, F. W. J., Vrancken, S. L. F. J., van der Laan, L., van Weissenbruch, M. M., van Dijk, M., de Jonge, R. C. J., van der Hoeven, A., … van den Anker, J. N. (2022). Antibiotic stewardship in neonatal intensive care units in the Netherlands: Practice, barriers and facilitators. Journal of Maternal-Fetal & Neonatal Medicine, 35(5), 861–870. https://doi.org/10.1080/14767058.2020.1732342
17. Horwood, C., Misiani, E., Mooko, M., Wadula, J., Verwey, C., Madhi, S. A., Bamford, C., Dramowski, A., Kissoon, N., Maunganidze, L., Mhlanga, M., Talavera, J., Chikobvu, P., Takuva, S., Farley, J., Esau, T., … Whitelaw, A. (2021). Implementing antimicrobial stewardship in a neonatal intensive care unit in a low-resource setting: Lessons learnt. Antimicrobial Resistance & Infection Control, 10(1), 121. https://doi.org/10.1186/s13756-021-00989-6
18. Yang, Q., Zhao, C., Gu, B., Li, Y., Zhang, W., Liu, H., Wang, X., Chen, J., Xu, Y., Zhou, L., Sun, L., Huang, H., Tang, S., Feng, Y., Li, Q., Guo, P., Wu, J., Zhao, Y., … Liu, Z. (2021). Multicenter study of antimicrobial resistance in Enterobacteriaceae isolates from Chinese hospitals. Frontiers in Cellular and Infection Microbiology, 11, 694093. https://doi.org/10.3389/fcimb.2021.694093
19. Tamma, P. D., Miller, M. A., & Cosgrove, S. E. (2021). Rethinking how antibiotics are prescribed: Incorporating behavioral science into antibiotic stewardship. Clinical Infectious Diseases, 73(2), 271–280. https://doi.org/10.1093/cid/ciaa554
20. Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S., & Kyrpides, N. C. (2021). A genomic catalog of Earth’s microbiomes. Nature Microbiology, 6(4), 512–523. https://doi.org/10.1038/s41564-021-00870-7
21. Kononova, N. A., Vlasenko, A. A., & Shakhov, V. N. (2020). Antimicrobial resistance in neonatal intensive care units: Modern challenges.
22. Dinh, A., Fain, V., Duran, C., Boucher, A., Péan, Y., Lemaignen, A., Lesprit, P., Plesiat, P., Tattevin, P., Le Turnier, P., Lefort, A., Montravers, P., Bru, J.-P., Schlemmer, B., Wolff, M., Allaouchiche, B., Leone, M., Vicaut, E., Bernard, L., … Timsit, J.-F. (2024). Antibiotic stewardship interventions in a French hospital: Impact on resistance and cost. Clinical Microbiology and Infection, 30(1), 38–43. https://doi.org/10.1016/j.cmi.2023.07.023
23. Cunin, P., Lemaitre, M., Lacroix, J., Gras-Le Guen, C., Cambonie, G., Danan, C., Simon, N., Benisty, S., Lamy, B., Gras-Le Guen, M., Bonacorsi, S., Levy, C., Cohen, R., Raymond, J., Caseris, M., Mignot, C., Polin, R. A., Aujard, Y., Tubiana, S., … Levy-Bruhl, D. (2024). Evaluation of empiric antibiotic use in neonatal sepsis: A populationbased study. JAMA Network Open, 7(11), e2441596. https://doi.org/10.1001/jamanetworkopen.2024.41596
24. Kolesnichenko, S. I., Lavrinenko, A. V., & Akhmaltdinova, L. L. (2021). Bloodstream infection etiology among children and adults. International Journal of Microbiology, 2021, 6657134. https://doi.org/10.1155/2021/6657134
25. PharmNews Kazakhstan. (2024). Dorozhnaia karta po sderzhivaniiu ustoichivosti k protivomikrobnym preparatam na 2023–2027 gg (Roadmap for Containing Antimicrobial Resistance 2023–2027) [in Russian]. Electronic resource. Access mode: https://pharmnewskz.com/ru/news/sovershenstvuetsya-nacionalnaya-sistema-nadzora-zaantimikrobnoy-rezistentnostyu_23898
26. Gordon, S. M., & O’Connell, A. E. (2021). Inborn errors of immunity in the premature infant: challenges in recognition and diagnosis. Frontiers in Immunology, 12, 758373. https://doi.org/10.3389/fimmu.2021.758373
27. Sampah, M. E., & Hackam, D. J. (2021). Prenatal immunity and influences on necrotizing enterocolitis and associated neonatal disorders. Frontiers in Immunology, 12, 650709. https://doi.org/10.3389/fimmu.2021.650709
28. Romanelli, R. M. C., Souza, G. G., Fontis, J. P., Rodrigues, J. H. P., Viana, J. P. R., Rocha, K. O., Tarabai, B. H. M., & Anchieta, L. M. (2025). Risk factors for colonization/infection by resistant microorganisms in outbreaks in neonatal unit: A systematic review and meta‑analysis. Journal of Pediatrics (Rio de Janeiro), 101(3), 297–311. https://doi.org/10.1016/j.jped.2024.12.005
29. Kartikeswar, G. A. P., Parikh, T. B., Randive, B., Kinikar, A., Rajput, U. C., Valvi, C., Vaidya, U., Malwade, S., Agarkhedkar, S., Kadam, A., Smith, R. M., Westercamp, M., Schumacher, C., Mave, V., Robinson, M. L., Gupta, A., Milstone, A. M., Manabe, Y. C., & Johnson, J. (2023). Bloodstream infections in neonates with central venous catheters in three tertiary neonatal intensive care units in Pune, India. Journal of Neonatal‑Perinatal Medicine, 16(3), 507–516. https://doi.org/10.3233/NPM-221110
30. Lange, A., Hijazi, K., Jauneikaite, E., Marchesi, F., Hinsu, A., & Sheikh, A. (2021). Transmission of Gram‑negative bacteria in neonatal intensive care units: Epidemiology, mechanisms and prevention. Frontiers in Pediatrics, 9, 722701. https://doi.org/10.3389/fped.2021.722701
31. Chavignon, M., Saliba, F., Soulier, A., Sotto, A., Lavigne, J. P., & Le Monnier, A. (2021). Molecular epidemiology of extended‑spectrum beta‑lactamase‑producing Enterobacteriaceae in a NICU: Environmental reservoir and cross‑transmission. Infection Control & Hospital Epidemiology, 42(2), 200–207. https://doi.org/10.1017/ice.2020.462
32. Yeung, C. H. T., Verstegen, R. H. J., Greenberg, R., & Lewis, T. R. (2023). Pharmacokinetic and pharmacodynamic principles: Unique considerations for optimal design of neonatal clinical trials. Frontiers in Pediatrics, 11, Article 1345969. https://doi.org/10.3389/fped.2023.1345969
33. Simeoli, R., Cairoli, S., Decembrino, N., Campi, F., Dionisi Vici, C., Corona, A., & Goffredo, B. M. (2022). Use of antibiotics in preterm newborns. Antibiotics (Basel), 11(9), 1142. https://doi.org/10.3390/antibiotics11091142
34. Mulinge, M. M., Mwanza, S. S., Kabahweza, H. M., Gudo, E. S. C., Ma, Y., & Manji, K. P. (2023). The impact of neonatal intensive care unit antibiotics on gut bacterial microbiota of preterm infants: A systematic review. Frontiers in Microbiomes, 2, 1180565. https://doi.org/10.3389/frmbi.2023.1180565
35. Zimmermann, P., & Curtis, N. (2023). Antibiotics at the beginning of life: Impact on the gut microbiome and resistome during infancy. Nature Communications, 14(1), 2423. https://doi.org/10.1038/s41467-023-38156-7
36. Cantey, J. B., & Patel, S. J. (2020). Antimicrobial stewardship in the NICU. Infectious Disease Clinics of North America, 34(2), 15–27. https://doi.org/10.1016/j.idc.2020.01.008
37. Rompola, J. L., Bashir, M. S., Cantey, J. B., & Patel, S. J. (2023). Factors associated with prolonged antibiotic therapy in neonates: A single‑center analysis. Infectious Disease Clinics of Practice, 31(4), 210–215. https://doi.org/10.1097/ICP.0000000000001234
38. Li, P., Chang, X., Chen, X., Wang, C., Shang, Y., Zheng, D., & Qi, K. (2022). Early‑life antibiotic exposure increases the risk of childhood overweight and obesity in relation to dysbiosis of gut microbiota: A birth cohort study. Annals of Clinical Microbiology and Antimicrobials, 21, 46. https://doi.org/10.1186/s12941-022-00535-1
39. Margetaki, K., Stratakis, N., Roumeliotaki, T., Karachaliou, M., Alexaki, M., Kogevinas, M., Chatzi, L., & Vafeiadi, M. (2021). Antibiotic use during pregnancy and infancy and risk factors for child growth, obesity and cardiovascular disease: The Rhea mother–child cohort, Crete, Greece. Pediatric Obesity, 16(11), e12843. https://doi.org/10.1111/ijpo.12843
40. Pauwels, I., Versporten, A., Ashiru‑Oredope, D., Figueiredo Costa, S., Maldonado, H., Matos Porto, A. P., Mehtar, S., Goossens, H., Anthierens, S., & Vlieghe, E. (2025). Implementation of hospital antimicrobial stewardship programmes in low‑ and middle‑income countries: A qualitative study from a multi‑professional perspective in the Global‑PPS network. Antimicrobial Resistance & Infection Control, 14(1), 26. https://doi.org/10.1186/s13756-025-01541-6
41. Abdel Hadi, H., Eltayeb, F., Al Balushi, S., Daghfal, J., Ahmed, F., & Mateus, C. (2024). Evaluation of hospital antimicrobial stewardship programs: Implementation, process, impact, and outcomes. Antibiotics (Basel), 13(3), 253. https://doi.org/10.3390/antibiotics13030253
42. World Health Organization. (2022). Antimicrobial stewardship programmes in health care facilities in low‑and middle‑income countries: A WHO practical toolkit. Geneva: WHO. Website. [Cited 14 Jan 2025]. Available from
URL: https://www.who.int/publications/i/item/9789241515481
43. Donà, D., Barbieri, E., Daverio, M., Lundin, R., Giaquinto, C., Zaoutis, T., & Sharland, M. (2020). Implementation and impact of pediatric antimicrobial stewardship programs: A systematic scoping review. Antimicrobial Resistance & Infection Control, 9(1), 3. https://doi.org/10.1186/s13756-020-0665-3
44. Rajar, P., Saugstad, O. D., Berild, D., Dutta, A., Greisen, G., Lausten‑Thomsen, U., Mande, S. S., Nangia, S., Petersen, F. C., Dahle, U. R., & Haaland, K. (2020). Antibiotic stewardship in premature infants: A systematic review. Neonatology, 117(6), 673–686. https://doi.org/10.1159/000511710
45. Lim, C., Ashley, E. A., Hamers, R. L., Turner, P., Kesteman, T., Akech, S., Corso, A., Mayxay, M., Okeke, I. N., Limmathurotsakul, D., & van Doorn, H. R. (2021). Surveillance strategies using routine microbiology for antimicrobial resistance in low‑ and middle‑income countries: Implications for local empirical treatment guidelines. Clinical Microbiology and Infection, 27(10), 1391–1399. https://doi.org/10.1016/j.cmi.2021.05.037 Cent.Asian J. Med. 2025, 1 (2), cajm011
46. Kuzmenkov, A. Y., Vinogradova, A. G., Trushin, I. V., & Kozlov, R. S. (2022). Practice of local antibiotic resistance monitoring at hospitals in various regions of the Russian Federation. Clinical Microbiology and Antimicrobial Chemotherapy, 24(1), 31–38. https://doi.org/10.36488/cmac.2022.1.31-38
47. Giovannenze, F., Del Vecchio, P., Frondizi, F., Rando, E., Leanza, G. M., Gross, M. M., Frater, A., Magrini, E., Liguoro, B., Sangiorgi, F., Fantoni, M., Torti, C., & Murri, R. (2025). Effect of an educational antimicrobial stewardship program on antibiotic prescriptions’ appropriateness in three medical units of a large university hospital: An interrupted time series analysis. Journal of Hospital Infection, 162, 127–135. https://doi.org/10.1016/j.jhin.2025.05.017
48. Catanzaro, M. T. (2022). Antibiotic stewardship for nurses: Using e‑learning modules to bridge the education gap. Antimicrobial Stewardship & Healthcare Epidemiology, 2(1), e7. https://doi.org/10.1017/ash.2021.216
49. Ibrahim, N. A., Bakry, M. M., Mohd Tahir, N. A. M., Mohd Zaini, N. R. M., & Shah, N. M. (2020). A prospective cohort study of factors associated with empiric antibiotic de‑escalation in neonates suspected with early onset sepsis (EOS). Pediatric Drugs, 22(3), 321–330. https://doi.org/10.1007/s40272-020-00388-1
50. Schwenk, H. T., Kruger, J. F., Sacks, L. D., Wood, M. S., Qureshi, L., & Bio, L. L. (2021). Use of prospective audit and feedback to reduce antibiotic exposure in a pediatric cardiac ICU. Pediatric Critical Care Medicine, 22(3), e224–e232. https://doi.org/10.1097/PCC.0000000000002608
51. Kosherova, Z., Zhazykhbayeva, D., Aimurziyeva, A., Kuntuganova, A., Manatova, A., & Semenova, Y. (2025). A systematic review: antimicrobial consumption surveillance and stewardship efforts in the former USSR countries. Electronic resource. Access mode: https://sciforum.net/paper/view/22954
52. Semenova, Y., Yergaliyeva, A., Aimurziyeva, A., Manatova, A., Kuntuganova, A., Makalkina, L., Aldiyarova, N., Semenov, D., & Lim, L. (2024). A nationwide evaluation of antibiotic consumption in Kazakhstan from 2019 to 2023. Antibiotics (Basel), 13(12), 1123. https://doi.org/10.3390/antibiotics13121123
53. World Health Organization. (2020). Defined Daily Dose (DDD): Otsused medikamentide tarbimise analüüsimiseks. WHO Collaborating Centre for Drug Statistics Methodology. Website. [Cited 20 January 2025]. Available from URL: https://www.whocc.no/ddd/
54. Fernández Barrantes, C., Ramos Esquivel, A., Hernández Soto, L. E., Chacón, M., Quesada, S., & López, E. (2024). Trends in antimicrobial consumption in tertiary care hospitals in Costa Rica from 2017 to 2021: A comparative analysis of defined daily doses per 100 bed days and per 100 discharges. Antibiotics (Basel), 13(10), 939. https://doi.org/10.3390/antibiotics13100939
55. Reuland, E. A., de Greeff, S. C., Schilder, A. G. M., Goessens, W. H. F., Verbon, A., & Melles, D. C. (2020). Impact of changes in the WHO’s 2019 update of DDDs on the consumption indicators in community antibiotic use. JAC Antimicrobial Resistance, 2(4), dlaa079. https://doi.org/10.1093/jacamr/dlaa079
56. Zhussupova, G., Utepova, D., Orazova, G., Akhmetova, Z., Yessmagambetova, A., & Soiak, K. (2021). Evaluation of antibiotic use in Kazakhstan for the period 2017–2019 based on WHO AWaRe classification. Antibiotics (Basel), 10(1), 58. https://doi.org/10.3390/antibiotics10010058
57. Oliveira, C. R. V., Almeida, I. A., de Oliveira‑Filho, A. D., & Boa‑Sorte, N. (2024). Profile of antimicrobial use and potential use of the defined daily dose in neonatology. Scientific Reports, 14, 22979. https://doi.org/10.1038/s41598-024-74559-2
58. de Bruin‑Scholten, M., van der Linden, P. D., & Stricker, B. H. (2020). Quantifying antibiotic use in paediatrics: A proposal for neonatal DDDs. Journal of Antimicrobial Chemotherapy, 75(11), 3125–3130. https://doi.org/10.1093/jac/dkaa330
59. Dalton, B. R., MacTavish, S. J., Bresee, L. C., Rajapakse, N., Vanderkooi, O., Vayalumkal, J., & Conly, J. (2015). Antimicrobial use over a four‑year period using days of therapy measurement at a Canadian pediatric acute Cent.Asian J. Med. 2025, 1 (2), cajm011
care hospital. Canadian Journal of Infectious Diseases & Medical Microbiology, 26(5), 253–258. https://doi.org/10.1155/2015/835209
60. Araujo da Silva, A. R., Marques, A., Di Biase, C., Martins, M. M., Oliveira, M. C., & Santos, A. P. (2020). Effectiveness of antimicrobial stewardship programmes in neonatology: A systematic review. Archives of Disease in Childhood Fetal and Neonatal Edition, 105(6), 563–568. https://doi.org/10.1136/archdischild-2019-318026
Загрузки
Опубликован
Выпуск
Раздел
Лицензия
Это произведение доступно по лицензии Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная.
