{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:58:34Z","timestamp":1781715514519,"version":"3.54.5"},"reference-count":104,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Council of Medical Science of the Medical University of Sofia (Sofia, Bulgaria)","award":["8201\/24.11.2023"],"award-info":[{"award-number":["8201\/24.11.2023"]}]},{"name":"Council of Medical Science of the Medical University of Sofia (Sofia, Bulgaria)","award":["D-100\/29.05.2024"],"award-info":[{"award-number":["D-100\/29.05.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Extensively drug-resistant P. aeruginosa (XDR-PA) has been highlighted as a serious public health threat. The present study aimed to explore the genomic characteristics of two Vietnamese extended-spectrum \u03b2-lactamase-9 (VEB-9)-producing XDR-PA isolates from Bulgaria in comparison to all blaVEB-9-positive strains with available genomes. The isolates designated Pae51 and Pae52 were obtained from tracheobronchial aspirates of intensive care unit (ICU) patients. Antimicrobial susceptibility testing, whole-genome sequencing, RT-qPCR, and phylogenomic analysis were performed. Pae51 and Pae52 were resistant to most antipseudomonal \u03b2-lactams including carbapenems, aminoglycosides, and fluoroquinolones but remained susceptible to colistin and cefiderocol. Numerous resistance determinants were detected: blaVEB-9, blaPDC-3, blaOXA-10, blaOXA-50, aac(6\u2032)-II, ant(2\u2033)-Ia, ant(3\u2033)-IIa, aph(3\u2032)-IIb, cprP, catB7, dfrB2, sul1, fosA, and tet(A). Both isolates carried complex integrons with blaVEB-9 and tet(A) embedded next to the conservative 3\u2032 end sequences. A variety of virulence factors were also identified, including the type III secretion system exotoxin U. Pae51 and Pae52 differed by only four SNPs and belonged to the high-risk clone ST357. To our knowledge, this is the first report of blaVEB-9-positive XDR-PA isolates in Bulgaria presenting a detailed genomic analysis. The development of novel antimicrobial strategies for such pathogens should be an essential part of infection control stewardship practices in ICU wards.<\/jats:p>","DOI":"10.3390\/pathogens13090719","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T03:59:09Z","timestamp":1724644749000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genomic Insights into Vietnamese Extended-Spectrum \u03b2-Lactamase-9-Producing Extensively Drug-Resistant Pseudomonas aeruginosa Isolates Belonging to the High-Risk Clone ST357 Obtained from Bulgarian Intensive Care Unit Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-1849","authenticated-orcid":false,"given":"Tanya","family":"Strateva","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology \u201cCorr. Mem. Prof. Ivan Mitov, MD, DMSc\u201d, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Stratev","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, University Multiprofile Hospital for Active Treatment \u2018St. Ivan Rilski\u2019, 15 Acad. Ivan Geshov Blvd., 1431 Sofia, Bulgaria"},{"name":"Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Medical University of Sofia, 1 St. Georgi Sofiyski Str., 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-9511","authenticated-orcid":false,"given":"Slavil","family":"Peykov","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology \u201cCorr. Mem. Prof. Ivan Mitov, MD, DMSc\u201d, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria"},{"name":"Department of Genetics, Faculty of Biology, University of Sofia \u2018St. Kliment Ohridski\u2019, 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria"},{"name":"BioInfoTech Laboratory, Sofia Tech Park, 111 Tsarigradsko Shose Blvd., 1784 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update","volume":"81","author":"Reynolds","year":"2021","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00031-19","DOI":"10.1128\/CMR.00031-19","article-title":"Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections","volume":"32","author":"Horcajada","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13054-021-03488-7","article-title":"Airway Pseudomonas aeruginosa Density in Mechanically Ventilated Patients: Clinical Impact and Relation to Therapeutic Efficacy of Antibiotics","volume":"25","author":"Migiyama","year":"2021","journal-title":"Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gomersall, J., Mortimer, K., Hassan, D., Whitehead, K.A., Slate, A.J., Ryder, S.F., Chambers, L.E., El Mohtadi, M., and Shokrollahi, K. (2023). Ten-Year Analysis of Bacterial Colonisation and Outcomes of Major Burn Patients with a Focus on Pseudomonas aeruginosa. Microorganisms, 12.","DOI":"10.3390\/microorganisms12010042"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41579-020-00477-5","article-title":"Pseudomonas aeruginosa Adaptation and Evolution in Patients with Cystic Fibrosis","volume":"19","author":"Rossi","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Paprocka, P., Durna\u015b, B., Ma\u0144kowska, A., Kr\u00f3l, G., Wollny, T., and Bucki, R. (2022). Pseudomonas aeruginosa Infections in Cancer Patients. Pathogens, 11.","DOI":"10.3390\/pathogens11060679"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jarzynka, S., Makarewicz, O., Weiss, D., Minkiewicz-Zochniak, A., Iwa\u0144ska, A., Skorupa, W., Padzik, M., Augustynowicz-Kope\u0107, E., and Ol\u0119dzka, G. (2023). The Impact of Pseudomonas aeruginosa Infection in Adult Cystic Fibrosis Patients\u2014A Single Polish Centre Study. Pathogens, 12.","DOI":"10.3390\/pathogens12121440"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"138","DOI":"10.22207\/JPAM.16.1.02","article-title":"Diabetic Foot Ulcer Infections and Pseudomonas aeruginosa Biofilm Production During the COVID-19 Pandemic","volume":"16","author":"Yakout","year":"2022","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Behzadi, P., Bar\u00e1th, Z., and Gajd\u00e1cs, M. (2021). It\u2019s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010042"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104806","DOI":"10.1016\/j.micinf.2021.104806","article-title":"Bacterial and Fungal Co-Infections among COVID-19 Patients in Intensive Care Unit","volume":"23","author":"Yang","year":"2021","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bongiovanni, M., and Barda, B. (2023). Pseudomonas aeruginosa Bloodstream Infections in SARS-CoV-2 Infected Patients: A Systematic Review. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062252"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104950","DOI":"10.1016\/j.micinf.2022.104950","article-title":"Therapeutic Approaches for Combating Pseudomonas aeruginosa Infections","volume":"24","author":"Jangra","year":"2022","journal-title":"Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Causap\u00e9, C., Cabot, G., Del Barrio-Tofi\u00f1o, E., and Oliver, A. (2018). The Versatile Mutational Resistome of Pseudomonas aeruginosa. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00685"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jean, S.-S., Harnod, D., and Hsueh, P.-R. (2022). Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.823684"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-Resistant, Extensively Drug-Resistant and Pandrug-Resistant Bacteria: An International Expert Proposal for Interim Standard Definitions for Acquired Resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1093\/cid\/ciy378","article-title":"Difficult-to-Treat Resistance in Gram-Negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-Line Agents","volume":"67","author":"Kadri","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.drup.2015.08.002","article-title":"The Increasing Threat of Pseudomonas aeruginosa High-Risk Clones","volume":"21\u201322","author":"Oliver","year":"2015","journal-title":"Drug Resist. Updates"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106196","DOI":"10.1016\/j.ijantimicag.2020.106196","article-title":"Pseudomonas aeruginosa Epidemic High-Risk Clones and Their Association with Horizontally-Acquired \u03b2-Lactamases: 2020 Update","volume":"56","author":"Oliver","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cmi.2023.12.026","article-title":"Pseudomonas aeruginosa Antimicrobial Susceptibility Profiles, Resistance Mechanisms and International Clonal Lineages: Update from ESGARS-ESCMID\/ISARPAE Group","volume":"30","author":"Oliver","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jurado-Mart\u00edn, I., Sainz-Mej\u00edas, M., and McClean, S. (2021). Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors. IJMS, 22.","DOI":"10.3390\/ijms22063128"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1042\/BCJ20200780","article-title":"A Pipeline to Evaluate Inhibitors of the Pseudomonas aeruginosa Exotoxin U","volume":"478","author":"Foulkes","year":"2021","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ijantimicag.2017.02.026","article-title":"Correlation between Phenotypic Antibiotic Susceptibility and the Resistome in Pseudomonas aeruginosa","volume":"50","author":"Jaillard","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1093\/jac\/dkz147","article-title":"Spanish Nationwide Survey on Pseudomonas aeruginosa Antimicrobial Resistance Mechanisms and Epidemiology","volume":"74","author":"Zamorano","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kabic, J., Fortunato, G., Vaz-Moreira, I., Kekic, D., Jovicevic, M., Pesovic, J., Ranin, L., Opavski, N., Manaia, C.M., and Gajic, I. (2023). Dissemination of Metallo-\u03b2-Lactamase-Producing Pseudomonas aeruginosa in Serbian Hospital Settings: Expansion of ST235 and ST654 Clones. IJMS, 24.","DOI":"10.21203\/rs.3.rs-2339123\/v1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1099\/jmm.0.009142-0","article-title":"Pseudomonas aeruginosa\u2014A Phenomenon of Bacterial Resistance","volume":"58","author":"Strateva","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dlab092","DOI":"10.1093\/jacamr\/dlab092","article-title":"Extended-Spectrum \u03b2 -Lactamases: An Update on Their Characteristics, Epidemiology and Detection","volume":"3","author":"Castanheira","year":"2021","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W282","DOI":"10.1093\/nar\/gky467","article-title":"The Microbial Genomes Atlas (MiGA) Webserver: Taxonomic and Gene Diversity Analysis of Archaea and Bacteria at the Whole Genome Level","volume":"46","author":"Gunturu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2024, July 05). Breakpoint Tables for Interpretation of MICs and Zone Diameters, Version 14.0. Available online: https:\/\/eucast.org."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/bioinformatics\/btt086","article-title":"QUAST: Quality Assessment Tool for Genome Assemblies","volume":"29","author":"Gurevich","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"The Galaxy Community, Afgan, E., Nekrutenko, A., Gr\u00fcning, B.A., Blankenberg, D., Goecks, J., Schatz, M.C., Ostrovsky, A.E., Mahmoud, A., and Lonie, A.J. (2022). The Galaxy Platform for Accessible, Reproducible and Collaborative Biomedical Analyses: 2022 Update. Nucleic Acids Res., 50, W345\u2013W351.","DOI":"10.1093\/nar\/gkac247"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D690","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: Expanded Curation, Support for Machine Learning, and Resistome Prediction at the Comprehensive Antibiotic Resistance Database","volume":"51","author":"Alcock","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1556\/030.2023.02060","article-title":"Imipenem Resistance Associated with Amino Acid Alterations of the OprD Porin in Pseudomonas aeruginosa Clinical Isolates","volume":"70","author":"Nazari","year":"2023","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D912","DOI":"10.1093\/nar\/gkab1107","article-title":"VFDB 2022: A General Classification Scheme for Bacterial Virulence Factors","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1128\/JCM.42.12.5644-5649.2004","article-title":"Development of a Multilocus Sequence Typing Scheme for the Opportunistic Pathogen Pseudomonas aeruginosa","volume":"42","author":"Curran","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1128\/JCM.00349-16","article-title":"Application of Whole-Genome Sequencing Data for O-Specific Antigen Analysis and In Silico Serotyping of Pseudomonas aeruginosa Isolates","volume":"54","author":"Thrane","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D646","DOI":"10.1093\/nar\/gkv1227","article-title":"Enhanced Annotations and Features for Comparing Thousands of Pseudomonas Genomes in the Pseudomonas Genome Database","volume":"44","author":"Winsor","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: Rapid Large-Scale Prokaryote Pan Genome Analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","article-title":"RAxML Version 8: A Tool for Phylogenetic Analysis and Post-Analysis of Large Phylogenies","volume":"30","author":"Stamatakis","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W293","DOI":"10.1093\/nar\/gkab301","article-title":"Interactive Tree Of Life (iTOL) v5: An Online Tool for Phylogenetic Tree Display and Annotation","volume":"49","author":"Letunic","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e02060-21","DOI":"10.1128\/mBio.02060-21","article-title":"TnCentral: A Prokaryotic Transposable Element Database and Web Portal for Transposon Analysis","volume":"12","author":"Ross","year":"2021","journal-title":"mBio"},{"key":"ref_47","unstructured":"European Centre for Disease Prevention and Control (2024). Healthcare-associated infections acquired in intensive care units. ECDC. Annual Epidemiological Report for 2020, ECDC. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/healthcare-associated-infections-acquired-intensive-care-units-annual."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Peykov, S., and Strateva, T. (2023). Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030651"},{"key":"ref_49","unstructured":"(2024, July 19). Antimicrobial Resistance Surveillance in Europe 2023\u20132021 Data. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/antimicrobial-resistance-surveillance-europe-2023-2021-data."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1080\/22221751.2020.1754133","article-title":"Colistin and Its Role in the Era of Antibiotic Resistance: An Extended Review (2000\u20132019)","volume":"9","author":"Zhong","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Coppola, N., Maraolo, A.E., Onorato, L., Scotto, R., Cal\u00f2, F., Atripaldi, L., Borrelli, A., Corcione, A., De Cristofaro, M.G., and Durante-Mangoni, E. (2022). Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion. Antibiotics, 11.","DOI":"10.3390\/antibiotics11091263"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1080\/14787210.2022.2071701","article-title":"Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Infections: A Case for Cefiderocol","volume":"20","author":"Canton","year":"2022","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_53","first-page":"S251","article-title":"Comparative In Vitro Activity of Meropenem\/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa","volume":"6","author":"Patel","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1093\/jac\/dkab252","article-title":"Activity of Meropenem\/Vaborbactam and Comparators against Gram-Negative Isolates from Eastern and Western European Patients Hospitalized with Pneumonia Including Ventilator-Associated Pneumonia (2014\u201319)","volume":"76","author":"Shortridge","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/cid\/ciac268","article-title":"Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum \u03b2-Lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)","volume":"75","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sid Ahmed, M.A., Khan, F.A., Hadi, H.A., Skariah, S., Sultan, A.A., Salam, A., Al Khal, A.L., S\u00f6derquist, B., Ibrahim, E.B., and Omrani, A.S. (2022). Association of blaVIM-2, blaPDC-35, blaOXA-10, blaOXA-488 and blaVEB-9 \u03b2-Lactamase Genes with Resistance to Ceftazidime\u2013Avibactam and Ceftolozane\u2013Tazobactam in Multidrug-Resistant Pseudomonas aeruginosa. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020130"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Muresu, N., Del Rio, A., Fox, V., Scutari, R., Alteri, C., Are, B.M., Terragni, P., Sechi, I., Sotgiu, G., and Piana, A. (2022). Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of \u03b2-Lactam\/\u03b2-Lactamase Inhibitor Combinations. Antibiotics, 12.","DOI":"10.3390\/antibiotics12010010"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/13543784.2018.1426745","article-title":"Cefiderocol: A Novel Siderophore Cephalosporin","volume":"27","author":"Choi","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00194-23","DOI":"10.1128\/aac.00194-23","article-title":"Cefiderocol Treatment for Patients with Multidrug\u2014And Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program","volume":"67","author":"Satlin","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","unstructured":"Shionogi Inc. (2021). Fetcroja (cefiderocol). Prescribing Information, Shionogi Inc.. Available online: https:\/\/www.shionogi.com\/content\/dam\/shionogi\/si\/products\/pdf\/fetroja.pdf."},{"key":"ref_61","unstructured":"European Medicines Agency (2024, July 20). Fetcroja (cefiderocol). An overview of Fetcroja and Why It Is Authorised in the EU. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/fetcroja."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S1473-3099(18)30554-1","article-title":"Cefiderocol versus Imipenem-Cilastatin for the Treatment of Complicated Urinary Tract Infections Caused by Gram-Negative Uropathogens: A Phase 2, Randomised, Double-Blind, Non-Inferiority Trial","volume":"18","author":"Portsmouth","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1473-3099(20)30731-3","article-title":"Cefiderocol versus High-Dose, Extended-Infusion Meropenem for the Treatment of Gram-Negative Nosocomial Pneumonia (APEKS-NP): A Randomised, Double-Blind, Phase 3, Non-Inferiority Trial","volume":"21","author":"Wunderink","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S1473-3099(20)30796-9","article-title":"Efficacy and Safety of Cefiderocol or Best Available Therapy for the Treatment of Serious Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria (CREDIBLE-CR): A Randomised, Open-Label, Multicentre, Pathogen-Focused, Descriptive, Phase 3 Trial","volume":"21","author":"Bassetti","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Losito, A.R., Raffaelli, F., Del Giacomo, P., and Tumbarello, M. (2022). New Drugs for the Treatment of Pseudomonas aeruginosa Infections with Limited Treatment Options: A Narrative Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11050579"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e02712-21","DOI":"10.1128\/spectrum.02712-21","article-title":"In Vitro Activity of Cefiderocol against U.S. and European Gram-Negative Clinical Isolates Collected in 2020 as Part of the SENTRY Antimicrobial Surveillance Program","volume":"10","author":"Shortridge","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cmi.2023.08.029","article-title":"Global Prevalence of Cefiderocol Non-Susceptibility in Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia: A Systematic Review and Meta-Analysis","volume":"30","author":"Karakonstantis","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1556\/030.2024.02309","article-title":"Genomic Insights into NDM-1-Producing Pseudomonas aeruginosa: Current Status in a Bulgarian Tertiary Hospital and on the Balkans","volume":"71","author":"Strateva","year":"2024","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Stoikov, I., Ivanov, I.N., Donchev, D., Teneva, D., Dobreva, E., Hristova, R., and Sabtcheva, S. (2023). Genomic Characterization of IMP-Producing Pseudomonas aeruginosa in Bulgaria Reveals the Emergence of IMP-100, a Novel Plasmid-Mediated Variant Coexisting with a Chromosomal VIM-4. Microorganisms, 11.","DOI":"10.20944\/preprints202307.2054.v1"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Glen, K.A., and Lamont, I.L. (2021). \u03b2-Lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects. Pathogens, 10.","DOI":"10.3390\/pathogens10121638"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00524-19","DOI":"10.1128\/msystems.00524-19","article-title":"Regulation of AmpC-Driven \u03b2-Lactam Resistance in Pseudomonas aeruginosa: Different Pathways, Different Signaling","volume":"4","author":"Torrens","year":"2019","journal-title":"mSystems"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3201\/eid0703.017322","article-title":"VEB-1-like Extended-Spectrum \u00df-Lactamases in Pseudomonas aeruginosa, Kuwait","volume":"7","author":"Poirel","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1128\/CMR.00019-15","article-title":"A Structure-Based Classification of Class A \u03b2-Lactamases, a Broadly Diverse Family of Enzymes","volume":"29","author":"Philippon","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1179\/joc.2007.19.2.140","article-title":"Widespread Detection of VEB-1-Type Extended-Spectrum Beta-Lactamases Among Nosocomial Ceftazidime-Resistant Pseudomonas aeruginosa Isolates in Sofia, Bulgaria","volume":"19","author":"Strateva","year":"2007","journal-title":"J. Chemother."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1099\/jmm.0.46986-0","article-title":"Problematic Clinical Isolates of Pseudomonas aeruginosa from the University Hospitals in Sofia, Bulgaria: Current Status of Antimicrobial Resistance and Prevailing Resistance Mechanisms","volume":"56","author":"Strateva","year":"2007","journal-title":"J. Med. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1089\/mdr.2013.0004","article-title":"Molecular Epidemiology and Multidrug Resistance Mechanisms of Pseudomonas aeruginosa Isolates from Bulgarian Hospitals","volume":"19","author":"Mulet","year":"2013","journal-title":"Microb. Drug Resist."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1128\/AAC.00047-16","article-title":"Identification of Novel VEB \u03b2-Lactamase Enzymes and Their Impact on Avibactam Inhibition","volume":"60","author":"Lahiri","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Laudy, A.E., R\u00f3g, P., Smoli\u0144ska-Kr\u00f3l, K., \u0106miel, M., S\u0142oczy\u0144ska, A., Patzer, J., Dzier\u017canowska, D., Wolinowska, R., Staro\u015bciak, B., and Tyski, S. (2017). Prevalence of ESBL-Producing Pseudomonas aeruginosa Isolates in Warsaw, Poland, Detected by Various Phenotypic and Genotypic Methods. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180121"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13756-020-00838-y","article-title":"\u03b2-Lactamase-Mediated Resistance in MDR-Pseudomonas aeruginosa from Qatar","volume":"9","author":"Khan","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ferous, S., Anastassopoulou, C., Pitiriga, V., Vrioni, G., and Tsakris, A. (2024). Antimicrobial and Diagnostic Stewardship of the Novel \u03b2-Lactam\/\u03b2-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa. Antibiotics, 13.","DOI":"10.3390\/antibiotics13030285"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1128\/AAC.02522-13","article-title":"Class D \u03b2-Lactamases: Are They All Carbapenemases?","volume":"58","author":"Antunes","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1128\/AAC.48.6.2043-2048.2004","article-title":"Biochemical Characterization of the Naturally Occurring Oxacillinase OXA-50 of Pseudomonas aeruginosa","volume":"48","author":"Girlich","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/14756366.2017.1344235","article-title":"Beta-Lactamase Database (BLDB)\u2014Structure and Function","volume":"32","author":"Naas","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1099\/jmm.0.001106","article-title":"First Detected OXA-50 Carbapenem-Resistant Clinical Isolates Pseudomonas aeruginosa from Bulgaria and Interplay between the Expression of Main Efflux Pumps, OprD and Intrinsic AmpC","volume":"68","author":"Petrova","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1046\/j.1469-0691.2001.00204.x","article-title":"Modified Hodge and EDTA-Disk Synergy Tests to Screen Metallo-\u03b2-Lactamase-Producing Strains of Pseudomonas and Acinetobacter Species","volume":"7","author":"Lee","year":"2001","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1128\/JCM.05602-11","article-title":"Sensitive and Specific Modified Hodge Test for KPC and Metallo-Beta- Lactamase Detection in Pseudomonas aeruginosa by Use of a Novel Indicator Strain, Klebsiella pneumoniae ATCC 700603","volume":"49","author":"Pasteran","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1089\/mdr.2019.0147","article-title":"Mutational Variation Analysis of oprD Porin Gene in Multidrug-Resistant Clinical Isolates of Pseudomonas aeruginosa","volume":"26","author":"Suresh","year":"2020","journal-title":"Microb. Drug Resist."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1128\/JB.187.4.1246-1253.2005","article-title":"Mutations in PA2491 (mexS) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa","volume":"187","author":"Sobel","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1093\/infdis\/jiw299","article-title":"Host and Pathogen Biomarkers for Severe Pseudomonas aeruginosa Infections","volume":"215","author":"Juan","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e00032-13","DOI":"10.1128\/mBio.00032-13","article-title":"Type III Secretion of ExoU Is Critical during Early Pseudomonas aeruginosa Pneumonia","volume":"4","author":"Howell","year":"2013","journal-title":"mBio"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/cid\/ciu866","article-title":"Influence of Virulence Genotype and Resistance Profile in the Mortality of Pseudomonas aeruginosa Bloodstream Infections","volume":"60","author":"Pena","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1086\/379372","article-title":"Secretion of the Toxin ExoU Is a Marker for Highly Virulent Pseudomonas aeruginosa Isolates Obtained from Patients with Hospital-Acquired Pneumonia","volume":"188","author":"Schulert","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1099\/00221287-147-10-2659","article-title":"Prevalence of Type III Secretion Genes in Clinical and Environmental Isolates of Pseudomonas aeruginosa","volume":"147","author":"Feltman","year":"2001","journal-title":"Microbiology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrmicro2199","article-title":"The Type III Secretion System of Pseudomonas aeruginosa: Infection by Injection","volume":"7","author":"Hauser","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1099\/jmm.0.018283-0","article-title":"Virulence Gene Distribution in Clinical, Nosocomial and Environmental Isolates of Pseudomonas aeruginosa","volume":"59","author":"Bradbury","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/1758-2229.12653","article-title":"Environmental Reservoirs for exoS+ and exoU+ Strains of Pseudomonas aeruginosa","volume":"10","author":"Rutherford","year":"2018","journal-title":"Env. Microbiol. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1128\/JCM.42.12.5783-5792.2004","article-title":"Genome Diversity of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients and the Hospital Environment","volume":"42","author":"Finnan","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Morales-Espinosa, R., Delgado, G., Espinosa, L.F., Isselo, D., M\u00e9ndez, J.L., Rodriguez, C., Miranda, G., and Cravioto, A. (2017). Fingerprint Analysis and Identification of Strains ST309 as a Potential High Risk Clone in a Pseudomonas aeruginosa Population Isolated from Children with Bacteremia in Mexico City. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00313"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"36","DOI":"10.34172\/ajcmi.2018.07","article-title":"Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas aeruginosa Isolates","volume":"5","author":"Rostami","year":"2017","journal-title":"Avicenna J. Clin. Microbiol. Infect."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Horna, G., Amaro, C., Palacios, A., Guerra, H., and Ruiz, J. (2019). High Frequency of the exoU+\/exoS+ Genotype Associated with Multidrug-Resistant \u201cHigh-Risk Clones\u201d of Pseudomonas aeruginosa Clinical Isolates from Peruvian Hospitals. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-47303-4"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.hlife.2023.02.001","article-title":"Emergence of Hypervirulent Pseudomonas aeruginosa Pathotypically Armed with Co-Expressed T3SS Effectors ExoS and ExoU","volume":"1","author":"Song","year":"2023","journal-title":"hLife"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e2164","DOI":"10.1002\/hsr2.2164","article-title":"High Prevalence of Multidrug-resistant Pseudomonas aeruginosa Carrying Integron and exoA, exoS, and exoU Genes Isolated from Burn Patients in Ahvaz, Southwest Iran: A Retrospective Study","volume":"7","author":"Akrami","year":"2024","journal-title":"Health Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e01759-19","DOI":"10.1128\/AAC.01759-19","article-title":"Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence","volume":"64","author":"Recio","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"R17","DOI":"10.1186\/cc13697","article-title":"Pseudomonas aeruginosa Serotypes in Nosocomial Pneumonia: Prevalence and Clinical Outcomes","volume":"18","author":"Lu","year":"2014","journal-title":"Crit. 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