{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:30:53Z","timestamp":1782937853850,"version":"3.54.5"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Pseudomonas aeruginosa is one of the leading causes of nosocomial respiratory tract infections, significantly affecting morbidity and mortality. It can persist in the lungs of patients with cystic fibrosis (CF) for extended periods because of its adaptive capacity. The main aim of this study was to determine the phenotypic and genotypic resistance to antibiotics of clinical isolates of P.\u00a0aeruginosa that persist in patients with CF receiving long-term antimicrobial therapy. The study included nine strains of P.\u00a0aeruginosa isolated from the sputum of patients with CF admitted to the hospital. Susceptibility to antibiotics was determined using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Whole-genome sequencing was performed for phylogeny, sequence typing, and to identify antibiotic-resistant genes. The study showed that during long-term persistence in the lungs of patients receiving antibacterial therapy, the restoration of susceptibility to antibiotics occurred in some cases. Multilocus sequence typing and phylogeny revealed six sequence types. Functional annotation identified 72 genes responsible for resistance to antibacterial and chemical substances, with either chromosomal or plasmid localisation.<\/jats:p>","DOI":"10.3390\/antibiotics14030302","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:07:51Z","timestamp":1741957671000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Resistance of Pseudomonas aeruginosa to Antibiotics During Long-Term Persistence in Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-068X","authenticated-orcid":false,"given":"Natalia","family":"Belkova","sequence":"first","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7656-342X","authenticated-orcid":false,"given":"Uliana","family":"Nemchenko","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-8816","authenticated-orcid":false,"given":"Elizaveta","family":"Klimenko","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3614-6631","authenticated-orcid":false,"given":"Nadezhda","family":"Smurova","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8522-7359","authenticated-orcid":false,"given":"Raisa","family":"Zugeeva","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sukhoreva","sequence":"additional","affiliation":[{"name":"Regional State Autonomous Healthcare Institution \u2018Ivano-Matreninskaya City Children\u2019s Clinical Hospital\u2019, 57, Sovetskaya Str., 664009 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-9590","authenticated-orcid":false,"given":"Viacheslav","family":"Sinkov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-6876","authenticated-orcid":false,"given":"Evgenij","family":"Savilov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution \u2018Scientific Centre for Family Health and Human Reproduction Problems\u2019, Epidemiology and Microbiology Institute, 3, K. Marks Str., 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s12275-019-9218-0","article-title":"Bacterial persistence: Fundamentals and clinical importance","volume":"57","author":"Jung","year":"2019","journal-title":"J. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kunnath, A.P., Suodha Suoodh, M., Chellappan, D.K., Chellian, J., and Palaniveloo, K. (2024). Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update. Br. J. Biomed. Sci., 81.","DOI":"10.3389\/bjbs.2024.12958"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41392-024-01866-5","article-title":"Bacterial persisters: Molecular mechanisms and therapeutic development","volume":"9","author":"Niu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00019-18","DOI":"10.1128\/CMR.00019-18","article-title":"Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis","volume":"31","author":"Parkins","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chandler, C.E., Hofstaedter, C.E., Hazen, T.H., Rasko, D.A., and Ernst, R.K. (2023). Genomic and Functional Characterization of Longitudinal Pseudomonas aeruginosa Isolates from Young Patients with Cystic Fibrosis. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.01556-23"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cohen-Cymberknoh, M. (Pediatr. Pulmonol, 2024). Infection and Inflammation in the Cystic fibrosis (CF) airway, Pediatr. Pulmonol, Early View.","DOI":"10.1002\/ppul.27355"},{"key":"ref_7","first-page":"15","article-title":"Mikrobnyy peyzazh nizhnikh dykhatel\u2019nykh putey u razlichnykh vozrastnykh grupp detey, bol\u2019nykh mukovistsidozom","volume":"87","author":"Shaginyan","year":"2010","journal-title":"J. Microbiol. Epidemiol. Immunobiol."},{"key":"ref_8","unstructured":"Cystic Fibrosis Foundation Patient Registry (2021). Annual Data Report, Cystic Fibrosis Foundation Patient Registry."},{"key":"ref_9","first-page":"mgen000513","article-title":"From genotype to phenotype: Adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment","volume":"7","author":"Camus","year":"2021","journal-title":"Microb. Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.36488\/cmac.2019.4.340-351","article-title":"Epidemiological significance of genome variations in Pseudomonas aeruginosa causing chronic lung infection in patients with cystic fibrosis","volume":"21","author":"Shaginyan","year":"2019","journal-title":"Clin. Microbiol. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/nrmicro2907","article-title":"Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: An evolutionary perspective","volume":"10","author":"Folkesson","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1111\/1462-2920.14093","article-title":"Single cell observations show persister cells wake based on ribosome content","volume":"20","author":"Kim","year":"2018","journal-title":"Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1099\/jmm.0.015875-0","article-title":"Fluctuations in phenotypes and genotypes within populations of Pseudomonas aeruginosa in the cystic fibrosis lung during pulmonary exacerbations","volume":"59","author":"Fothergill","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1128\/JCM.00802-13","article-title":"Population structure and antimicrobial susceptibility of both non persistent and persistent Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients","volume":"51","author":"Alba","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jhin.2015.09.010","article-title":"How and why to monitor Pseudomonas aeruginosa infections in the long term at a cystic fibrosis centre","volume":"92","author":"Kalferstova","year":"2016","journal-title":"J. Hosp. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1111\/j.1462-2920.2011.02483.x","article-title":"Microevolution of the major common Pseudomonas aeruginosa clones C and PA14 in cystic fibrosis lungs","volume":"13","author":"Cramer","year":"2011","journal-title":"Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Iwa\u0144ska, A., Trafny, E.A., Czopowicz, M., and Augustynowicz-Kope\u0107, E. (2023). Phenotypic and genotypic characteristics of Pseudomonas aeruginosa isolated from cystic fibrosis patients with chronic infections. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-39005-9"},{"key":"ref_18","unstructured":"(2025, February 04). The Comprehensive Antibiotic Resistance Database. Available online: https:\/\/card.mcmaster.ca\/aro\/3000777#resistomes-table."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1128\/AAC.00155-10","article-title":"Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii","volume":"54","author":"Coyne","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Puzari, M., and Chetia, P. (2017). RND efflux pump mediated antibiotic resistance in Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa: A major issue worldwide. World J. Microbiol. Biotechnol., 33.","DOI":"10.1007\/s11274-016-2190-5"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zwama, M., and Nishino, K. (2021). Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070774"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Athar, M., Gervasoni, S., Catte, A., Basciu, A., Malloci, G., Ruggerone, P., and Vargiu, A.V. (2023). Tripartite efflux pumps of the RND superfamily: What did we learn from computational studies?. Microbiology, 169.","DOI":"10.1099\/mic.0.001307"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kavanaugh, L.G., Dey, D., Shafer, W.M., and Conn, G.L. (2024). Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance. Microbiol. Mol. Biol. Rev., 88.","DOI":"10.1128\/mmbr.00089-23"},{"key":"ref_24","unstructured":"(2025, February 04). The Comprehensive Antibiotic Resistance Database. Available online: https:\/\/card.mcmaster.ca\/aro\/3005063."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00007-19","DOI":"10.1128\/CMR.00007-19","article-title":"Transferable Mechanisms of Quinolone Resistance from 1998 Onward","volume":"32","author":"Ruiz","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e02629-17","DOI":"10.1128\/AAC.02629-17","article-title":"CrpP Is a Novel Ciprofloxacin-Modifying Enzyme Encoded by the Pseudomonas aeruginosa pUM505 Plasmid","volume":"62","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1093\/jac\/dkz316","article-title":"CrpP, a passenger or a hidden stowaway in the Pseudomonas aeruginosa genome?","volume":"74","author":"Ruiz","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104574","DOI":"10.1016\/j.meegid.2020.104574","article-title":"Acquired fluoroquinolone resistance genes in corneal isolates of Pseudomonas aeruginosa","volume":"85","author":"Khan","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00489-20","DOI":"10.1128\/AAC.00489-20","article-title":"Pathogenicity Genomic Island-Associated CrpP-Like Fluoroquinolone-Modifying Enzymes among Pseudomonas aeruginosa Clinical Isolates in Europe","volume":"64","author":"Nordmann","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1007\/s10096-021-04287-2","article-title":"The prevalence and functional characteristics of CrpP-like in Pseudomonas aeruginosa isolates from China","volume":"40","author":"Xu","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1080\/21505594.2021.1962160","article-title":"Diversification and prevalence of the quinolone resistance crpP genes and the crpP-carrying Tn6786-related integrative and conjugative elements in Pseudomonas aeruginosa","volume":"12","author":"Zhu","year":"2021","journal-title":"Virulence"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101082","DOI":"10.1016\/j.nmni.2023.101082","article-title":"First report of CrpP prevalence in a South American country","volume":"51","author":"Ruiz","year":"2023","journal-title":"New Microbes New Infect."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hu, Z., Zhou, L., Tao, X., Li, P., Zheng, X., Zhang, W., and Tan, Z. (2024). Antimicrobial resistance survey and whole-genome analysis of nosocomial P. aeruginosa isolated from eastern Province of China in 2016-2021. Ann. Clin. Microbiol. Antimicrob., 23.","DOI":"10.1186\/s12941-023-00656-1"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Garc\u00eda, M., Garc\u00eda-Castillo, M., Garc\u00eda-Fern\u00e1ndez, S., L\u00f3pez-Mendoza, D., D\u00edaz-Rega\u00f1\u00f3n, J., Romano, J., P\u00e1ssaro, L., Paix\u00e3o, L., and Cant\u00f3n, R. (2021). Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain. Microorganisms., 9.","DOI":"10.3390\/microorganisms9020388"},{"key":"ref_35","first-page":"e71118","article-title":"Molecular Characterization of Pseudomonas aeruginosa Clinical Isolates Through Whole-Genome Sequencing: A Comprehensive Analysis of Biotypes, Sequence Types, and Antimicrobial and Virulence Genes","volume":"16","author":"Bharadwaj","year":"2024","journal-title":"Cureus"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wu, W., Huang, J., and Xu, Z. (2024). Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications. Microb. Biotechnol., 17.","DOI":"10.1111\/1751-7915.14487"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e01081-19","DOI":"10.1128\/AAC.01081-19","article-title":"Cinnamaldehyde induces expression of efflux pumps and multidrug resistance in Pseudomonas aeruginosa","volume":"63","author":"Tetard","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dubois, E., Spasovski, V., Pl\u00e9siat, P., and Llanes, C. (2025). Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde. Microbiol. Spectr., 13.","DOI":"10.1128\/spectrum.01699-24"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nageeb, W., Amin, D.H., Mohammedsaleh, Z.M., and Makharita, R.R. (2021). Novel Molecular Markers Linked to Pseudomonas aeruginosa Epidemic High-Risk Clones. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010035"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nageeb, W.M., and Hetta, H.F. (2022). The predictive potential of different molecular markers linked to amikacin susceptibility phenotypes in Pseudomonas aeruginosa. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267396"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1128\/AAC.02284-12","article-title":"KpnEF, a new member of the Klebsiella pneumoniae cell envelope stress response regulon, is an SMR-type efflux pump involved in broad-spectrum antimicrobial resistance","volume":"57","author":"Srinivasan","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","unstructured":"Nemchenko, U.M., Belkova, N.L., Klimenko, E.S., Smurova, N.E., and Savilov, E.D. (2024). Phenotypic and genetic variability of clinical isolates of Pseudomonas aeruginosa persisting in patients with cystic fibrosis. Klin. Mikrobiol. Antimikrobn. Himioter., 26, (In Russian)."},{"key":"ref_43","first-page":"88","article-title":"Identification of Infectious Diseases Patterns in the Combined Use of Bacteriological Diagnostics and MALDI Biotyper","volume":"5","author":"Voropaeva","year":"2020","journal-title":"Acta Biomed. Sci."},{"key":"ref_44","unstructured":"(2025, January 24). The European Committee on Antimicrobial Susceptibility Testing\u2014EUCAST. Available online: http:\/\/www.eucast.org."},{"key":"ref_45","first-page":"53","article-title":"Biological properties and genetic structure of clinic isolates of Klebsiella pneumoniae species","volume":"9","author":"Belkova","year":"2024","journal-title":"Acta Biomed. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1093\/bioinformatics\/btp356","article-title":"Reordering contigs of draft genomes using the Mauve aligner","volume":"25","author":"Rissman","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"124","DOI":"10.12688\/wellcomeopenres.14826.1","article-title":"Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications","volume":"3","author":"Jolley","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1093\/jac\/dkaa345","article-title":"ResFinder 4.0 for predictions of phenotypes from genotypes","volume":"75","author":"Bortolaia","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","unstructured":"(2025, January 24). The Comprehensive Antibiotic Resistance Database. Available online: https:\/\/card.mcmaster.ca\/analyze\/rgi."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1128\/AAC.00419-13","article-title":"The comprehensive antibiotic resistance database","volume":"57","author":"McArthur","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","first-page":"D517","article-title":"CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database","volume":"48","author":"Alcock","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: Architecture and applications. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-421"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"W16","DOI":"10.1093\/nar\/gkw387","article-title":"PHASTER: A better, faster version of the PHAST phage search tool","volume":"44","author":"Arndt","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1101\/gr.232397.117","article-title":"GrapeTree: Visualization of core genomic relationships among 100,000 bacterial pathogens","volume":"28","author":"Zhou","year":"2018","journal-title":"Genome Res."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:05Z","timestamp":1760028845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["antibiotics14030302"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14030302","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]}}}