{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:13:44Z","timestamp":1784574824570,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H04664"],"award-info":[{"award-number":["17H04664"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Increase of extraintestinal pathogenic Escherichia coli (ExPEC) showing resistance to beta-lactams is a major public health concern. This study was conducted as a first molecular epidemiological study on ExPEC in Cuba, regarding prevalence of extended-spectrum beta-lactamases (ESBLs) and carbapenemase genes. A total of 306 ExPEC isolates collected in medical institutions in 16 regions in Cuba (2014\u20132018) were analyzed for their genotypes and presence of genes encoding ESBL, carbapenemase, plasmid-mediated quinolone resistance (PMQR) determinants by PCR and sequencing. The most common phylogenetic group of ExPEC was B2 (49%), followed by D (23%), A (21%), and B1 (7%). Among ESBL genes detected, blaCTX-M was the most common and detected in 61% of ExPEC, with blaCTX-M-15 being dominant and distributed to all the phylogenetic groups. NDM-1 type carbapenemase gene was identified in two isolates of phylogenetic group B1-ST448. Phylogenetic group B2 ExPEC belonged to mostly ST131 (or its single-locus variant) with O25b allele, harboring blaCTX-M-27, and included an isolate of emerging type ST1193. aac (6\u2019)-Ib-cr was the most prevalent PMQR gene (40.5%), being present in 54.5% of CTX-M-positive isolates. These results indicated high prevalence of CTX-M genes and the emergence of NDM-1 gene among recent ExPEC in Cuba, depicting an alarming situation.<\/jats:p>","DOI":"10.3390\/pathogens9010065","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T07:39:02Z","timestamp":1579246742000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["High Prevalence of CTX-M Type Extended-Spectrum Beta-Lactamase Genes and Detection of NDM-1 Carbapenemase Gene in Extraintestinal Pathogenic Escherichia coli in Cuba"],"prefix":"10.3390","volume":"9","author":[{"given":"Dianelys","family":"Qui\u00f1ones","sequence":"first","affiliation":[{"name":"Department of Bacteriology-Mycology, Pedro Kour\u00ed Institute of Tropical Medicine, Havana 17100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8402-5349","authenticated-orcid":false,"given":"Meiji Soe","family":"Aung","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenisel","family":"Carmona","sequence":"additional","affiliation":[{"name":"Department of Bacteriology-Mycology, Pedro Kour\u00ed Institute of Tropical Medicine, Havana 17100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Karla","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Bacteriology-Mycology, Pedro Kour\u00ed Institute of Tropical Medicine, Havana 17100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niurka","family":"Pereda","sequence":"additional","affiliation":[{"name":"Department of Bacteriology-Mycology, Pedro Kour\u00ed Institute of Tropical Medicine, Havana 17100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Microbiology Department, H\u00e9roes de Baire Hospital, Isla de La Juventud 25100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayrelis","family":"Rivero","sequence":"additional","affiliation":[{"name":"Microbiology Department, Enrique Cabrera hospital, Havana 10400, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Zayas","sequence":"additional","affiliation":[{"name":"Microbiology Department, Juan Bruno Zayas Hospital, Santiago de Cuba 90100, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7923","authenticated-orcid":false,"given":"Rosa","family":"del Campo","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Hospital, 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-567X","authenticated-orcid":false,"given":"Noriko","family":"Urushibara","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-6211","authenticated-orcid":false,"given":"Nobumichi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/1469-0691.12646","article-title":"Pandemic lineages of extraintestinal pathogenic Escherichia coli","volume":"20","author":"Riley","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00135-18","DOI":"10.1128\/CMR.00135-18","article-title":"Global Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages","volume":"32","author":"Manges","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1128\/AAC.01169-07","article-title":"Clinical and economic impact of common multidrug-resistant gram-negative bacilli","volume":"52","author":"Giske","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S1473-3099(08)70041-0","article-title":"Extended-spectrum beta-lactamase-producing Enterobacteriaceae: An emerging public-health concern","volume":"8","author":"Pitout","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/jac\/dkx146","article-title":"Global epidemiology of CTX-M \u03b2-lactamases: Temporal and geographical shifts in genotype","volume":"72","author":"Bevan","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1128\/JCM.00219-10","article-title":"Extended-spectrum-beta-lactamase, AmpC, and Carbapenemase issues","volume":"48","author":"Thomson","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/CMR.00036-08","article-title":"AmpC beta-Lactamases","volume":"22","author":"Jacoby","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.molmed.2012.03.003","article-title":"Carbapenem resistance in Enterobacteriaceae: Here is the storm!","volume":"18","author":"Nordmann","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/1469-0691.12719","article-title":"The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide","volume":"20","author":"Nordmann","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"976273","DOI":"10.1155\/2012\/976273","article-title":"Global fluoroquinolone resistance epidemiology and implications for clinical use","volume":"2012","author":"Dalhoff","year":"2012","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Poirel, L., Madec, J.Y., Lupo, A., Schink, A.K., Kieffer, N., Nordmann, P., and Schwarz, S. (2018). Antimicrobial Resistance in Escherichia coli. Microbiol. Spectr., 6.","DOI":"10.1128\/microbiolspec.ARBA-0026-2017"},{"key":"ref_12","first-page":"52","article-title":"Phenotypic and molecular identification of extended-spectrum beta-lactamase (ESBL) TEM and SHV produced by clinical isolates Escherichia coli and Klebsiella spp. in hospitals","volume":"59","author":"Alvarez","year":"2007","journal-title":"Rev. Cubana Med. Trop."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ijantimicag.2016.04.021","article-title":"Tigecycline antimicrobial activity tested against clinical bacteria from Latin American medical centres: Results from SENTRY Antimicrobial Surveillance Program (2011\u20132014)","volume":"48","author":"Sader","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.diagmicrobio.2012.04.007","article-title":"Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: Results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008\u20132010)","volume":"73","author":"Gales","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1128\/AAC.00666-12","article-title":"Prevalence and molecular characterization of extended-spectrum-\u03b2-lactamase-producing Enterobacteriaceae in a pediatric patient population","volume":"56","author":"Chandramohan","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"iv64","DOI":"10.1093\/jac\/dkz289","article-title":"Canadian Antimicrobial Resistance Alliance (CARA) and CANWARD. Dramatic rise in the proportion of ESBL-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates identified in Canadian hospital laboratories from 2007 to 2016","volume":"74","author":"Denisuik","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1128\/CMR.00125-13","article-title":"Escherichia coli ST131, an intriguing clonal group","volume":"27","author":"Bertrand","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.3201\/eid2211.160519","article-title":"Global Escherichia coli Sequence Type 131 Clade with blaCTX-M-27 Gene","volume":"22","author":"Matsumura","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12941-018-0265-x","article-title":"Genetic contexts related to the diffusion of plasmid-mediated CTX-M-55 extended-spectrum beta-lactamase isolated from Enterobacteriaceae in China","volume":"17","author":"Hu","year":"2018","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1128\/AEM.00522-13","article-title":"Molecular characterization of CTX-M \u03b2-lactamase and associated addiction systems in Escherichia coli circulating among cattle, farm workers, and the farm environment","volume":"79","author":"Tamang","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01269-19","DOI":"10.1128\/MRA.01269-19","article-title":"Complete Circular Genome Sequence of a Multidrug-Resistant Escherichia coli Strain from Cuba Obtained with Nanopore and Illumina Hybrid Assembly","volume":"8","author":"Brilhante","year":"2019","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jgar.2019.06.008","article-title":"Frequency distribution, genotypes and prevalent sequence types of New Delhi metallo-\u03b2-lactamase-producing Escherichia coli among clinical isolates around the world: A review","volume":"19","author":"Dadashi","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249856","DOI":"10.1155\/2014\/249856","article-title":"Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria","volume":"2014","author":"Dortet","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.3389\/fmicb.2017.02078","article-title":"A Multiplex SYBR Green Real-Time PCR Assay for the Detection of Three Colistin Resistance Genes from Cultured Bacteria, Feces, and Environment Samples","volume":"8","author":"Li","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1128\/AAC.00055-15","article-title":"Outbreak caused by Enterobacteriaceae harboring NDM-1 metallo-\u03b2-lactamase carried in an IncFII plasmid in a tertiary care hospital in Mexico City","volume":"59","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bocanegra-Ibarias, P., Garza-Gonz\u00e1lez, E., Morf\u00edn-Otero, R., Barrios, H., Villarreal-Trevi\u00f1o, L., Rodr\u00edguez-Noriega, E., Garza-Ramos, U., Petersen-Morfin, S., and Silva-Sanchez, J. (2017). Molecular and microbiological report of a hospital outbreak of NDM-1-carrying Enterobacteriaceae in Mexico. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179651"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.nmni.2015.06.002","article-title":"High prevalence of blaOXA-23 in Acinetobacter spp. and detection of blaNDM-1 in A. soli in Cuba: Report from National Surveillance Program (2010\u20132012)","volume":"7","author":"Carvajal","year":"2015","journal-title":"New Microbes New Infect."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alsharapy, S.A., Gharout-Sait, A., Muggeo, A., Guillard, T., Cholley, P., Brasme, L., Bertrand, X., Moghram, G.S., Touati, A., and De Champs, C. (2019). Characterization of Carbapenem-Resistant Enterobacteriaceae Clinical Isolates in Al Thawra University Hospital, Sana\u2019a, Yemen. Microb. Drug Resist.","DOI":"10.1089\/mdr.2018.0443"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1128\/AAC.04040-14","article-title":"Molecular characterization of blaNDM-5 carried on an IncFII plasmid in an Escherichia coli isolate from a nontraveler patient in Spain","volume":"59","author":"Pitart","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/jac\/dku055","article-title":"Emergence of a multiresistant KPC-3 and VIM-1 carbapenemase-producing Escherichia coli strain in Spain","volume":"69","author":"Undabeitia","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e01913-18","DOI":"10.1128\/AAC.01913-18","article-title":"Phylogenomic Analysis of Extraintestinal Pathogenic Escherichia coli Sequence Type 1193, an Emerging Multidrug-Resistant Clonal Group","volume":"63","author":"Johnson","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01664-18","DOI":"10.1128\/JCM.01664-18","article-title":"Rapid Emergence, Subsidence, and Molecular Detection of Escherichia coli Sequence Type 1193-fimH64, a New Disseminated Multidrug-Resistant Commensal and Extraintestinal Pathogen","volume":"57","author":"Johnson","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jgar.2019.01.014","article-title":"First report of the new emerging global clone ST1193 among clinical isolates of extended-spectrum \u03b2-lactamase (ESBL)-producing Escherichia coli from Germany","volume":"17","author":"Valenza","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_34","first-page":"96","article-title":"Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017","volume":"75","author":"Birgy","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jacoby, G.A., Strahilevitz, J., and Hooper, D.C. (2014). Plasmid-mediated quinolone resistance. Microbiol. Spectr., 2.","DOI":"10.1128\/microbiolspec.PLAS-0006-2013"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1111\/j.1365-2958.2006.05172.x","article-title":"Sex and virulence in Escherichia coli: An evolutionary perspective","volume":"60","author":"Wirth","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_37","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2020, January 15). Clinical Breakpoints-Bacteria v 6.0; 2016. Available online: http:\/\/www.eucast.org\/clinical_breakpoints\/."},{"key":"ref_38","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2014). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute (CLSI). Twenty-Fourth Informational Supplement, M100-S24."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1111\/j.1600-0463.2007.00722.x","article-title":"Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae","volume":"115","author":"Monstein","year":"2007","journal-title":"APMIS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1099\/jmm.0.46160-0","article-title":"Rapid and simple detection of blaCTX-M genes by multiplex PCR assay","volume":"54","author":"Xu","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.diagmicrobio.2010.12.002","article-title":"Multiplex PCR for detection of acquired carbapenemase genes","volume":"70","author":"Poirel","year":"2011","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1128\/JCM.40.6.2153-2162.2002","article-title":"Detection of plasmid-mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR","volume":"40","author":"Hanson","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_43","unstructured":"National Center for Biotechnology Information (2020, January 15). Basic Local Alignment Search Tool (BLAST), Available online: https:\/\/blast.ncbi.nlm.nih.gov\/Blast.cgi."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1099\/jmm.0.064428-0","article-title":"Development and evaluation of a multiplex PCR for eight plasmid-mediated quinolone-resistance determinants","volume":"62","author":"Ciesielczuk","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1128\/AEM.66.10.4555-4558.2000","article-title":"Rapid and simple determination of the Escherichia coli phylogenetic group","volume":"66","author":"Clermont","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1093\/jac\/dkn084","article-title":"The CTX-M-15-producing Escherichia coli diffusing clone belongs to a highly virulent B2 phylogenetic subgroup","volume":"61","author":"Clermont","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/infdis\/jis933","article-title":"Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli","volume":"207","author":"Johnson","year":"2013","journal-title":"J. Infect. Dis."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:05:15Z","timestamp":1760364315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,16]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["pathogens9010065"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9010065","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,16]]}}}