Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1778410.15789/2220-7619-NAF-17784REVIEWSОБЗОРЫReview ArticleNew approaches for combating polyresistant ESKAPE pathogensСовременные подходы к борьбе c полирезистентными патогенами группы ESKAPEKonkovaL. S.КоньковаЛ. С.
Russian Federation

Junior Researcher, Laboratory of Medical Bacteriology

младший научный сотрудник лаборатории медицинской бактериологии

lykraeva@yandex.ruRogachevaE. V.РогачеваЕ. В.
Russian Federation

PhD (Biology), Junior Researcher, Laboratory of Medical Bacteriology

к.б.н., младший научный сотрудник лаборатории медицинской бактериологии

lykraeva@yandex.ruKraevaL. A.КраеваЛ. А.
Russian Federation

DSc (Medicine), Associate Professor, Head of the Laboratory of Medical Bacteriology, Professor of the Department of Microbiology

д.м.н., доцент, зав. лабораторией медицинской бактериологии, профессор кафедры микробиологии

lykraeva@yandex.ruSt. Petersburg Pasteur InstituteФБУН НИИ эпидемиологии и микробиологии имени ПастераMilitary Medical Academy named after S.M. KirovФГБВОУ ВО Военно-медицинская академия имени С.М. Кирова МО РФ20012025080720251522352462609202421122024Copyright ©; 2025, Konkova L.S., Rogacheva E.V., Kraeva L.A.Copyright ©; 2025, Конькова Л.С., Рогачева E.В., Краева Л.A.2025Konkova L.S., Rogacheva E.V., Kraeva L.A.Конькова Л.С., Рогачева E.В., Краева Л.A.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17784

Antibiotic resistance of microorganisms is the most pressing global health problem due to the ever-increasing number of deaths caused by ineffective antibiotic therapy. The COVID-19 pandemic has only exacerbated pre-existing issue of increasing resistance of bacterial strains worldwide. Lack of public awareness about proper use of antibiotics directly impacts on uncontrolled antibiotic administration associated with weak antibiotic dispensing controls as well as limited access to health facilities in low- and middle-income countries. It is reported that 68.9% of COVID-19 patients used antibiotics for prophylaxis against bacterial complications or to treat coronavirus infection (mainly azithromycin and ceftriaxone) before hospitalization, with a self-medication rate of 33.0%. The most antibiotic-resistant and dangerous to global public health group of microorganisms is known as ESKAPE: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species. The proportion of resistant strains among these microorganisms can reach 95%. In light of the rapid increase in the number of infections caused by antibiotic-resistant strains, a need to create new antibacterial drugs is the most urgent task. The development of new antibiotics is a high-cost goal and it’s often ineffective. Therefore, more and more often their developers resort to the use of antibiotics combinations or using them together with adjuvants of different mechanisms of action. In recent years, special devices and coatings with nanoparticles of various metals deposited on their surface have become increasingly widespread. Some successes achieved in the use of antimicrobial peptides have been leveled by the loss of activity in the human body and their high production cost. In this regard, the use of bacteriophages, especially in combination with antibiotics, has been becoming a promising approach. The observed synergism both in vitro and in vivo experiments allow to hope for certain successes in the fight against ESKAPE group multidrug-resistant pathogens.

Антибиотикорезистентность микроорганизмов — наиболее актуальная проблема мирового здравоохранения, обусловленная все более возрастающим количеством смертей по причине неэффективной антибактериальной терапии. Пандемия COVID-19 лишь усугубила и без того существующую проблему нарастания резистентности штаммов бактерий во всем мире. Отсутствие осведомленности населения об адекватном применении антибиотиков оказало прямое влияние на их бесконтрольное применение, связанное со слабыми мерами контроля отпуска антибиотиков, а также ограниченным доступом к медицинским учреждениям в странах с низким и средним уровнем доходов. Сообщается, что 68,9% пациентов с COVID-19 использовали антибиотики в качестве профилактики бактериальных осложнений либо для лечения коронавирусной инфекции (в основном азитромицин и цефтриаксон) до госпитализации, при этом уровень самолечения составил 33,0%. Наиболее устойчивая к антибиотикам и опасная для мирового здравоохранения группа микроорганизмов известна как ESKAPE: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species. При этом доля резистентных штаммов среди этих микроорганизмов может достигать 95%. В свете стремительного роста количества случаев инфекций, вызванных антибиотикорезистентными штаммами, необходимость создания новых антибактериальных препаратов является наиболее актуальной задачей. Разработка новых антибиотиков высокозатратна и зачастую малоэффективна. Поэтому все чаще их разработчики прибегают к использованию комбинаций антибиотиков или сочетанию их с адъювантами с разным механизмом действия. В последние годы все более широкое распространение получают специальные устройства и покрытия с нанесенными на их поверхность наночастицами различных металлов. Некоторые успехи, достигнутые при использовании антимикробных пептидов, были нивелированы потерей активности в организме человека и высокой стоимостью их производства. В связи с этим перспективным направлением становится использование бактериофагов, особенно в сочетании с антибиотиками. Наблюдаемый при этом синергизм, как в экспериментах in vitro, так и in vivo, позволяет надеяться на определенные успехи в борьбе c полирезистентными патогенами группы ESKAPE.

antibiotic resistancemultidrug resistancegram-negative bacteriagram-positive bacteriaphage-antibiotic synergyESKAPE pathogensантибиотикорезистентностьмножественная лекарственная устойчивостьграмположительные бактерииграмотрицательные бактериибактерии группы ESKAPEсинергизм фагов с антибиотикамиАкимкин В.Г., Тутельян А.В., Шулакова Н.И., Воронин Е.М. Пандемия COVID-19: новый виток нарастания антибиотикорезистентности // Инфекционные болезни. 2021. Т. 19, № 3. С. 133–138. [Акимкин В.Г., Тутельян А.В., Шулакова Н.И., Воронин Е.М. Пандемия COVID-19: новый виток нарастания антибиотикорезистентности. Infektsionnye bolezni = Infectious Diseases, 2021, vol. 19, no. 3, pp. 133–138. (In Russ.)] doi: 10.20953/1729-9225-2021-3-133-1382021 Antibacterial agents in clinical and preclinical development: an overview and analysis. Geneva: World Health Organization, 2022. URL: https://www.researchgate.net/publication/362630806_2021_Antibacterial_agents_in_clinical_and_preclinical_development_an_overview_and_analysisAhmed A., Azim A., Gurjar M., Baronia A. Current concepts in combination antibiotic therapy for critically ill patients. Indian J. Crit. Care Med., 2014, vol. 18, no. 5, pp. 310–314. doi: 10.4103/0972-5229.132495Ahmed S., Raqib R., Guðmundsson G., Bergman P., Agerberth B., Rekha R. Host-directed therapy as a novel treatment strategy to overcome tuberculosis: targeting immune modulation. Antibiotics, 2020, vol. 9, no. 1: 21. doi: 10.3390/antibiotics9010021Baronia A., Ahmed A. Current concepts in combination antibiotic therapy for critically ill patients. Indian J. Crit. Care Med., 2014, vol. 18, no. 5, pp. 310–314. doi: 10.4103/0972-5229.132495Barrio-Tofiño E., López-Causapé C., Oliver A. Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases. Int. J. Antimicrob. Agents, 2020, vol. 56, no. 6, pp. 106–126. doi: 10.1016/j.ijantimicag.2020.106196Berglund N., Piggot T., Jefferies D., Sessions R., Bond P., Khalid S. Interaction of the antimicrobial peptide polymyxin B1 with both membranes of E. coli: a molecular dynamics study. PLoS Comput. Biol., 2015, vol. 11, no. 4, pp. 1004–1018. doi: 10.1371/journal.pcbi.1004180Bernal P., Molina-Santiago C., Daddaoua A., Llamas M. Antibiotic adjuvants: Identification and clinical use. Microb. Biotechnol., 2013, vol. 6, no. 5, pp. 445–449. doi: 10.1111/1751-7915.12044Björn C., Mahlapuu M., Mattsby-Baltzer I., Håkansson J. Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r. Peptides (NY), 2016, vol. 81, pp. 21–28. doi: 10.1016/j.peptides.2016.08.004Bonomo R., Szabo D. Mechanisms of multidrug resistance in acinetobacter species and Pseudomonas aeruginosa. Clin. Infect. Dis., 2006, vol. 43, no. 2, pp. 49–56. doi: 10.1086/504477Brüssow H. Phage therapy: the Escherichia coli experience. Microbiology, 2005, vol. 151, pp. 2133–2140. doi: 10.1099/mic.0.27849-0Cai Y., Wang J., Liu X., Wang R., Xia L. A review of the combination therapy of low frequency ultrasound with antibiotics. Biomed. Res. Int., 2017, vol. 2017, pp. 1–14. doi: 10.1155/2017/2317846Cano E., Caflisch K., Bollyky P., Van Belleghem J., Patel R., Fackler J. Phage therapy for limb-threatening prosthetic knee Klebsiella pneumoniae infection: case report and in vitro characterization of anti-biofilm activity. Clin. Infect. Dis., 2021, vol. 73, no. 1, pp. 144–151. doi: 10.1093/cid/ciaa705Castanheira M., Kimbrough J., DeVries S., Mendes R., Sader H. Trends of β-lactamase occurrence among Escherichia coli and Klebsiella pneumoniae in United States Hospitals during a 5-year period and activity of antimicrobial agents against isolates stratified by β-lactamase type. Open Forum Infect. Dis., 2023, vol. 10, no. 2, pp. 1–11. doi: 10.1093/ofid/ofad038Chan B., Turner P., Kim S., Mojibian H., Elefteriades J., Narayan D. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol. Med. Public Health, 2018, vol. 2018, no. 1, pp. 60–66. doi: 10.1093/emph/eoy005Chang S., Hsieh S., Chen M., Sheng W., Chen Y. Oral fusidic acid fails to eradicate methicillin-resistant Staphylococcus aureus colonization and results in emergence of fusidic acid-resistant strains. Diagn. Microbiol. Infect. Dis., 2000, vol. 36, no. 2, pp. 131–136. doi: 10.1016/s0732-8893(99)00116-9.Chatterjee A., Chakraborty R., Basu T. Mechanism of antibacterial activity of copper nanoparticles. Nanotechnology, 2014, vol. 25, no. 13, pp. 101–135. doi: 10.1088/0957-4484/25/13/135101Chawla M., Verma J., Gupta R., Das B. Antibiotic potentiators against multidrug-resistant bacteria: discovery, development, and clinical relevance. Front. Microbiol., 2022, vol. 13, pp. 1–19. doi: 10.3389/fmicb.2022.887251Chen P., Wu Z., Leung A., Chen X., Landao-Bassonga E., Gao J. Fabrication of a silver nanoparticle-coated collagen membrane with anti-bacterial and anti-inflammatory activities for guided bone regeneration. Biomedical Materials, 2018, vol. 13, no. 6, pp. 14–25. doi: 10.1088/1748-605X/aae15bChernousova S., Epple M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew. Chem. Int. Ed. Engl., 2013, vol. 52, no. 6, pp. 1636–1653. doi: 10.1002/anie.201205923Chinemerem Nwobodo D., Ugwu M., Oliseloke A., Al-Ouqaili M., Chinedu I., Victor C. Antibiotic resistance: the challenges and some emerging strategies for tackling a global menace. J. Clin. Lab. Anal., 2022, vol. 36, pp. 1–10. doi: 10.1002/jcla.24655Comeau A., Tétart F., Trojet S., Prère M., Krisch H. Phage-antibiotic synergy (PAS): β-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS One, 2007, vol. 2, no. 8, pp. 1–4. doi: 10.1371/journal.pone.0000799Coronado-Álvarez N., Parra D., Parra-Ruiz J. Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci. Enferm. Infecc. Microbiol. Clin., 2019, vol. 37, no. 1, pp. 4–10. doi: 10.1016/j.eimc.2018.05.009Dąbrowska K. Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review. Med. Res. Rev., 2019, vol. 39, pp. 2000–2025. doi: 10.1002/med.21572Denissen J., Reyneke B., Waso-Reyneke M., Havenga B., Barnard T., Khan S. Prevalence of ESKAPE pathogens in the environment: antibiotic resistance status, community-acquired infection and risk to human health. Int. J. Hyg. Environ. Health, 2022, vol. 244: 114006. doi: 10.1016/j.ijheh.2022.114006Diallo K., Dublanchet A. A Century of clinical use of phages: a literature review. Antibiotics, 2023, vol. 751, vol. 12, no. 4: 751. doi: 10.3390/antibiotics12040751Dickey J., Perrot V. Adjunct phage treatment enhances the effectiveness of low antibiotic concentration against Staphylococcus aureus biofilms in vitro. PLoS One, 2019, vol. 14, no. 1, pp. 1–17. doi: 10.1371/journal.pone.0209390Diekema D., Pfaller M., Shortridge D., Zervos M., Jones R. Twenty-year trends in antimicrobial susceptibilities among Staphylococcus aureus from the SENTRY Antimicrobial Surveillance Program. Open Forum Infect. Dis., 2019, vol. 6, pp. 47–53. doi: 10.1093/ofid/ofy270Domingo-Calap P., Delgado-Martínez J. Bacteriophages: protagonists of a post-antibiotic era. Antibiotics, 2018, vol. 7, no. 3: 66. doi: 10.3390/antibiotics7030066Drawz S., Bonomo R. Three decades of β-lactamase inhibitors. Clin. Microbiol. Rev., 2010, vol. 23, pp. 160–201. doi: 10.1128/CMR.00037-09Du H., Puri S., McCall A., Norris H., Russo T., Edgerton M. Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens. Front. Cell. Infect. Microbiol., 2017, vol. 7, pp. 1–12. doi: 10.3389/fcimb.2017.00041Durante-Mangoni E., Signoriello G., Andini R., Mattei A., De Cristoforo M., Murino P. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin. Infect. Dis., 2013, vol. 57, no. 3, pp. 349–358. doi: 10.1093/cid/cit253Ezraty B., Gennaris A., Barras F., Collet J. Oxidative stress, protein damage and repair in bacteria. Nat. Rev. Microbiol, 2017, vol. 15, no. 7, pp. 385–396. doi: 10.1038/nrmicro.2017.26Fauconnier A. Phage therapy regulation: from night to dawn. Viruses, 2019, vol. 11, no. 4, pp. 1–8. doi: 10.3390/v11040352Franco D., Calabrese G., Guglielmino S., Conoci S. Metal-based nanoparticles: antibacterial mechanisms and biomedical application. Microorganisms, 2022, vol. 10, no. 9: 1778. doi: 10.3390/microorganisms10091778Galiano K., Pleifer C., Engelhardt K., Brössner G., Lackner P., Huck C. Silver segregation and bacterial growth of intraventricular catheters impregnated with silver nanoparticles in cerebrospinal fluid drainages. Neurol. Res., 2008, vol. 30, no. 3, pp. 285–287. doi: 10.1179/016164107X229902Ghosh A., Jayaraman N., Chatterji D. Small-molecule inhibition of bacterial biofilm. ACS Omega, 2020, vol. 5, no. 7, pp. 3108–3115. doi: 10.1021/acsomega.9b03695González-Bello C. Antibiotic adjuvants — a strategy to unlock bacterial resistance to antibiotics. Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 4221–4228. doi: 10.1016/j.bmcl.2017.08.027Hampton H., Watson B., Fineran P. The arms race between bacteria and their phage foes. Nature, 2020, vol. 577, pp. 327–336. doi: 10.1038/s41586-019-1894-8Hemeg H. Nanomaterials for alternative antibacterial therapy. Int. J. Nanomedicine, 2017, vol. 12, pp. 8211–8225. doi: 10.2147/IJN.S132163Hesse S., Rajaure M., Wall E., Johnson J., Bliskovsky V., Gottesman S. Phage resistance in multidrug-resistant Klebsiella pneumoniae st258 evolves via diverse mutations that culminate in impaired adsorption. mBio, 2020, vol. 11, no. 1, pp. 1–14. doi: 10.1128/mBio.02530-19Himmelweit F. Combined action of penicillin and bacteriophage on staphylococci. Lancet, 1945, vol. 246, pp. 104–105. doi: 10.1016/s0140-6736(45)91422-xIvask A., ElBadawy A., Kaweeteerawat C., Boren D., Fischer H., Ji Z. Toxicity mechanisms in Escherichia coli vary for silver nanoparticles and differ from ionic silver. ACS Nano, 2014, vol. 8, no. 1, pp. 374–386. doi: 10.1021/nn4044047Jahnke J., Cornejo J., Sumner J., Schuler A., Atanassov P., Ista L. Conjugated gold nanoparticles as a tool for probing the bacterial cell envelope: The case of Shewanella oneidensis MR-1. Biointerphases, 2016, vol. 11, no. 1: 011003. doi: 10.1116/1.4939244Johri A., Johri P., Hoyle N., Nadareishvili L., Pipia L., Nizharadze D. Case report: Successful treatment of recurrent E. coli infection with bacteriophage therapy for patient suffering from chronic bacterial prostatitis. Front. Pharmacol., 2023, vol. 14: 1243824. doi: 10.3389/fphar.2023.1243824Juan C., Peña C., Oliver A. Host and pathogen biomarkers for severe Pseudomonas aeruginosa infections. J. Infect. Dis, 2017, vol. 215, no. 1, pp. 44–51. doi: 10.1093/infdis/jiw299Kalia V. Quorum sensing inhibitors: an overview. Biotechnol. Adv., 2013, vol. 31, no. 2, pp. 224–245. doi: 10.1016/j.biotechadv.2012.10.004Khawaldeh A., Morales S., Dillon B., Alavidze Z., Ginn A., Thomas L. Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection. J. Med. Microbiol., 2011, vol. 60, no. 11, pp. 1697–1700. doi: 10.1099/jmm.0.029744-0Klem J., Dömötör D., Schneider G., Kovács T., Tóth A., Rákhely G. Bacteriophage therapy against staphylococci. Acta Microbiol. Immunol. Hung., 2013, vol. 60, no. 4, pp. 411–422. doi: 10.1556/AMicr.60.2013.4.3LaVergne S., Hamilton T., Biswas B., Kumaraswamy M., Schooley R., Wooten D. Phage therapy for a multidrug-resistant Acinetobacter baumannii craniectomy site infection. Open Forum Infect. Dis., 2018, vol. 5, no. 4: ofy064 doi: 10.1093/ofid/ofy064Law N., Logan C., Yung G., Furr C., Lehman S., Morales S. Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Infection, 2019, vol. 47, no. 4, pp. 665–668. doi: 10.1007/s15010-019-01319-0Lemire J., Harrison J., Turner R. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat. Rev. Microbiol, 2013, vol. 11, no. 6, pp. 371–384. doi: 10.1038/nrmicro3028Letkiewicz S., Międzybrodzki R., Fortuna W., Weber-Dąbrowska B., Górski A. Eradication of Enterococcus faecalis by phage therapy in chronic bacterial prostatitis — case report. Folia Microbiol (Praha), 2009, vol. 54, no. 5, pp. 457–461. doi: 10.1007/s12223-009-0064-zLin Q., Deslouches B., Montelaro R., Di Y. Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37. Int. J. Antimicrob. Agents, 2018, vol. 52, no. 5, pp. 667–672. doi: 10.1016/j.ijantimicag.2018.04.019Lister P., Wolter D., Hanson N. Antibacterial-resistant Pseudomonas aeruginosa : clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin. Microbiol. Rev., 2009, vol. 22, no. 4, pp. 582–610. doi: 10.1128/CMR.00040-09Liu J., Liu J., Attarilar S., Wang C., Tamaddon M., Yang C. Nano-modified titanium implant materials: a way toward improved antibacterial properties. Front. Bioeng. Biotechnol., 2020, no. 8: 576969 doi: 10.3389/fbioe.2020.576969Lu L., Fu R., Li C., Yu C., Li Z., Guan H. Silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) nanofibers as wound dressings: a preclinical study. Int. J. Nanomedicine, 2013, vol. 8, no. 1, pp. 4131–4145. doi: 10.2147/IJN.S51679Luong T., Salabarria A., Roach D. Phage therapy in the resistance era: where do we stand and where are we going? Clinical Therapeutics, 2020, vol. 42, pp. 1659–1680. doi: 10.1016/j.clinthera.2020.07.014Mahlapuu M., Håkansson J., Ringstad L., Björn C. Antimicrobial peptides: an emerging category of therapeutic agents. Front Cell. Infect. Microbiol., 2016, vol. 6: 194. doi: 10.3389/fcimb.2016.00194Mahlapuu M., Antimicrobial peptides as therapeutic agents: opportunities and challenges. Crit. Rev. Biotechnol., 2020, vol. 40, no. 7, pp. 978–992. doi: 10.1080/07388551.2020.1796576Mammari N., Lamouroux E., Boudier A., Duval R. Current knowledge on the oxidative-stress-mediated antimicrobial properties of metal-based nanoparticles. Microorganisms, 2022, vol. 10, no. 2, pp. 437–448. doi: 10.3390/microorganisms10020437Manchanda V., Sanchaita S., Singh N. Multidrug resistant Acinetobacter. J. Glob. Infect. Dis, 2010, vol. 2, no. 3, pp. 293–302. doi: 10.4103/0974-777X.68538Mancuso G., Midiri A., Gerace E., Biondo C. Bacterial antibiotic resistance: the most critical pathogens. Pathogens, 2021, vol. 10, pp. 116–126. doi: 10.3390/pathogens10101310Mandal S., Roy A., Ghosh A., Hazra T., Basak A., Franco O. Challenges and future prospects of antibiotic therapy: from peptides to phages utilization. Front. Pharmacol., 2014, vol. 5, pp. 105–117. doi: 10.3389/fphar.2014.00105Maragakis L., Perl T. Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin. Infect. Dis., 2008, vol. 146, pp. 1254–1263. doi: 10.1086/529198Melander R., Melander C. The challenge of overcoming antibiotic resistance: an adjuvant approach? ACS Infect. Dis., 2017, vol. 3, no. 8, pp. 559–563. doi: 10.1021/acsinfecdis.7b00071Miller W., Arias C. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nat. Rev. Microbiol, 2024, vol. 10, pp. 598–616. doi: 10.1038/s41579-024-01054-wMiller W., Murray B., Rice L., Arias C. Resistance in vancomycin-resistant enterococci. Infect. Dis. Clin. North Am., 2020, vol. 34, no. 4, pp. 751–771. doi: 10.1016/j.idc.2020.08.004Mohanty S., Mishra S., Jena P., Jacob B., Sarkar B., Sonawane A. An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles. Nanomedicine, 2012, vol. 8, no. 6, pp. 916–924. doi: 10.1016/j.nano.2011.11.007Mulani M., Kamble E., Kumkar S., Tawre M., Pardesi K. Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: a review. Front. Microbiol., 2019, vol. 10, pp. 539–563. doi: 10.3389/fmicb.2019.00539Murray C., Ikuta K., Sharara F., Swetschinski L., Robles Aguilar G., Gray A. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet, 2022, vol. 399, pp. 629–655. doi: 10.1016/S0140-6736(21)02724-0Nichols W., Newell P., Critchley I., Riccobene T., Das S. Avibactam pharmacokinetic/pharmacodynamic targets. Antimicrob. Agents Chemother., 2018, vol. 62, no. 6: e02446-17. doi: 10.1128/AAC.02446-17De Oliveira D., Forde B., Kidd T., Harris P., Schembri M., Beatson S. Antimicrobial resistance in ESKAPE pathogens. Clin. Microbiol. Rev., 2020, vol. 33, no. 3, pp. 181–190. doi: 10.1128/CMR.00181-19Papp-Wallace K., Bonomo R. New β-lactamase inhibitors in the clinic. Infect. Dis. Clin. North Am., 2016, vol. 30, no. 2, pp. 441–464. doi: 10.1016/j.idc.2016.02.007Pfaller M., Cormican M., Flamm R., Mendes R., Jones R. Temporal and geographic variation in antimicrobial susceptibility and resistance patterns of Enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997–2016. Open Forum Infect. Dis., 2019, vol. 6, pp. 54–62. doi: 10.1093/ofid/ofy344Pfalzgraff A., Brandenburg K., Weindl G. Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds. Front. Pharmacol., 2018, vol. 9: 281. doi: 10.3389/fphar.2018.00281Pirnay J., Verbeken G., Ceyssens P., Huys I., de Vos D., Ameloot C., Fauconnier A. The magistral phage. Viruses, 2018, vol. 10, no. 2: 64. doi: 10.3390/v10020064Podschun R., Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin. Microbiol. Rev., 1998, vol. 11, no. 4, pp. 589–603. doi: 10.1128/CMR.11.4.589Poirel L., Madec J., Lupo A., Schink A., Kieffer N., Nordmann P. Antimicrobial resistance in Escherichia coli. Microbiol. Spectr., 2018, vol. 6, no. 4: 10. doi: 10.1128/microbiolspec.ARBA-0026-2017Ramalingam B., Parandhaman T., Das S. Antibacterial effects of biosynthesized silver nanoparticles on surface ultrastructure and nanomechanical properties of gram-negative bacteria viz. Escherichia coli and Pseudomonas aeruginosa. ACS Appl. Mater. Interfaces, 2016, vol. 8, no. 7, pp. 4963–4976. doi: 10.1021/acsami.6b00161Ramirez D., Ramirez D., Arthur G., Zhanel G., Schweizer F. Guanidinylated Polymyxins as outer membrane permeabilizers capable of potentiating rifampicin, erythromycin, ceftazidime and aztreonam against gram-negative bacteria. Antibiotics, 2022, vol. 11, no. 10: 1277. doi: 10.3390/antibiotics11101277Ranjan S., Ramalingam C. Titanium dioxide nanoparticles induce bacterial membrane rupture by reactive oxygen species generation. Environ. Chem. Lett., 2016, vol. 14, no. 4, pp. 487–494. doi: 10.1007/s10311-016-0586-yRhoads D., Wolcott R., Kuskowski M., Wolcott B., Ward L., Sulakvelidze A. Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. J. Wound Care, 2009, vol. 18, no. 6, pp. 237–243. doi: 10.12968/jowc.2009.18.6.42801Rios A., Moutinho C., Pinto F., Del Fiol F., Jozala A., Chaud M. Alternatives to overcoming bacterial resistances: state-of-the-art. Microbiol. Res., 2016, vol. 191, pp. 51–80. doi: 10.1016/j.micres.2016.04.008Rodríguez-Baño J., Gutiérrez-Gutiérrez B., Machuca I., Pascual A. Treatment of infections caused by extended-spectrum-beta-lactamase-, Ampc-, and carbapenemase-producing enterobacteriaceae. Clin. Microbiol. Rev., 2018, vol. 31, no. 2, pp. 79–87. doi: 10.1128/CMR.00079-17Rubalskii E., Ruemke S., Salmoukas C., Boyle E., Warnecke G., Tudorache I. Bacteriophage therapy for critical infections related to cardiothoracic surgery. Antibiotics, 2020, vol. 9, no. 5, pp. 232–244. doi: 10.3390/antibiotics9050232Sapkota J., Sharma M., Shrestha D., Jha B. Antimicrobial susceptibility pattern of Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolated from sputum in a tertiary care hospital. Journal of Institute of Medicine Nepal, 2019, vol. 41, no. 3, pp. 59–62. doi: 10.3126/jiom.v41i3.37367Shortridge D., Gales A., Streit J., Huband M., Tsakris A., Jones R. Geographic and temporal patterns of antimicrobial resistance in pseudomonas aeruginosa over 20 years from the SENTRY Antimicrobial Surveillance Program, 1997–2016. Open Forum Infect. Dis., 2019, vol. 6, pp. 63–68. doi: 10.1093/ofid/ofy343Simon K., Pier W., Krüttgen A., Horz H. Synergy between phage sb-1 and oxacillin against methicillin-resistant staphylococcus aureus. Antibiotics, 2021, vol. 10, no. 7, pp. 849–858. doi: 10.3390/antibiotics10070849Sirelkhatim A., Mahmud S., Seeni A., Kaus N., Ann L., Bakhori S. Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nanomicro Lett., 2015, vol. 7, no. 3, pp. 219–242. doi: 10.1007/s40820-015-0040-xSnyder A., Werth B., Nonejuie P., McRoberts J., Pogliano J., Sakoulas G. Fosfomycin enhances the activity of daptomycin against vancomycin-resistant enterococci in an in vitro pharmacokinetic-pharmacodynamic model. Antimicrob. Agents Chemother., 2016, vol. 60, no. 10, pp. 5716–5723. doi: 10.1128/AAC.00687-16Spirescu V., Chircov C., Grumezescu A., Vasile B., Andronescu E. Inorganic nanoparticles and composite films for antimicrobial therapies. Int. J. Mol. Sci., 2021, vol. 22, no. 9, pp. 4595–4620. doi: 10.3390/ijms22094595Tagliaferri T., Jansen M., Horz H. Fighting pathogenic bacteria on two fronts: phages and antibiotics as combined strategy. Front. Cell. Infect. Microbiol., 2019, vol. 9, pp. 22–35. doi: 10.3389/fcimb.2019.00022Tackling drug-resistant infections globally: final report and recommendations. Chaired by J. O’Neill. 2016. URL: https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdfThambirajoo M., Maarof M., Lokanathan Y., Katas H., Ghazalli N., Tabata Y. Potential of nanoparticles integrated with antibacterial properties in preventing biofilm and antibiotic resistance. Antibiotics, 2021, vol. 10, no. 11, pp. 1338–1364. doi: 10.3390/antibiotics10111338Thill A., Zeyons O., Spalla O., Chauvat F., Rose J., Auffan M. Cytotoxicity of CeO2 nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism. Environ. Sci. Technol., 2006, vol. 40, no. 19, pp. 6151–6156. doi: 10.1021/es060999bTindall B., Sutton G., Garrity G. Enterobacter aerogenes Hormaeche and Edwards 1960 (Approved Lists 1980) and Klebsiella mobilis Bascomb et al. 1971 (Approved Lists 1980) share the same nomenclatural type (ATCC 13048) on the Approved Lists and are homotypic synonyms, with consequences for the name Klebsiella mobilis Bascomb et al. 1971 (Approved Lists 1980). Int. J. Syst. Evol. Microbiol., 2017, vol. 67, no. 2, pp. 502–504. doi: 10.1099/ijsem.0.001572Tsonos J., Vandenheuvel D., Briers Y., De Greve H., Hernalsteens J., Lavigne R. Hurdles in bacteriophage therapy: deconstructing the parameters. Vet. Microbiol., 2014, vol. 171, no. 3, pp. 460–469. doi: 10.1016/j.vetmic.2013.11.001Uddin T., Chakraborty A., Khusro A., Zidan B., Mitra S., Emran T. Antibiotic resistance in microbes: history, mechanisms, therapeutic strategies and future prospects. J. Infect. Public Health, 2021, vol. 14, pp. 1750–1766. doi: 10.1016/j.jiph.2021.10.020Vazquez-Grande G., Kumar A. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy. Semin. Respir. Crit. Care Med., 2015, vol. 36, no. 1, pp. 154–166. doi: 10.1055/s-0034-1398742Vestergaard M., Paulander W., Marvig R., Clasen J., Jochumsen N., Molin S. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa. Int. J. Antimicrob. Agents, 2016, vol. 47, no. 1, pp. 48–55. doi: 10.1016/j.ijantimicag.2015.09.014Wang C., Hsieh Y., Powers Z., Kao C. Defeating antibiotic-resistant bacteria: exploring alternative therapies for a post-antibiotic era. Int. J. Mol. Sci., 2020, vol. 21, pp. 1061–1079. doi: 10.3390/ijms21031061Wang G., Li X., Zasloff M. A database view of naturally occurring antimicrobial peptides: nomenclature, classification and amino acid sequence analysis. In: Antimicrobial peptides: discovery, design and novel therapeutic strategies. Ed. by G. Wang. Wallingford: CABI, 2010, vol. 18, pp. 1–21. doi: 10.1079/9781845936570.0001WHO (2017). Global priority list of antibiotic-resistance bacteria to guide research, discovery, and development of new antibiotics.WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. URL: https://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1Wilson G., Fitzpatrick M., Walding K., Gonzalez B., Schweizer M., Suda K. Meta-analysis of clinical outcomes using ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam for the treatment of multidrug-resistant gram-negative infections. Open Forum Infect. Dis., 2021, vol. 8, no. 2: ofaa651. doi: 10.1093/ofid/ofaa651Wright G. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol., 2016, vol. 24, no. 11, pp. 862–871. doi: 10.1016/j.tim.2016.06.009Yahav D., Giske C., Grāmatniece A., Abodakpi H., Tam V., Leibovici L. New β-lactam–β-lactamase inhibitor combinations. Clin. Microbiol. Rev., 2020, vol. 34, no. 1, pp. 115–120. doi: 10.1128/CMR.00115-20Zhanel G., Chung P., Adam H., Zelenitsky S., Denisuik A., Schweizer F. Ceftolozane/tazobactam: a novel cephalosporin/ β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs, 2014, vol. 74, pp. 31–51. doi: 10.1007/s40265-013-0168-2Zhao C., Kristoffersson A., Khan D., Lagerbäck P., Lustig U., Cao S. Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model. Sci. Rep., 2024, vol. 14, no. 1, pp. 106–117. doi: 10.1038/s41598-024-61518-0