{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:26:17Z","timestamp":1791465977574,"version":"4.3.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This prospective study was carried out to investigate molecular characteristics and antimicrobial susceptibility patterns of <jats:italic>Citrobacter<\/jats:italic> spp. from extraintestinal infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty-six clinical <jats:italic>Citrobacter<\/jats:italic> spp. isolates were isolated from hospital patients with extraintestinal infections and analyzed by multilocus sequence typing (MLST) using seven housekeeping genes. Antimicrobial susceptibility testing was performed by disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. Adhesion and cytotoxicity to HEp-2 cells were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 46 clinical <jats:italic>Citrobacter<\/jats:italic> spp. isolates were typed into 38 sequence types (STs), 9 of which belonged to four clonal complexes (CCs). None of the isolates shared the same ST or CCs with isolates from other countries or from other parts of China. Over half of the isolates were multidrug-resistant (MDR), with 17\/26 C<jats:italic>. freundii<\/jats:italic>, 5\/6 C<jats:italic>. braakii<\/jats:italic>, and 3\/14 C<jats:italic>. koseri<\/jats:italic> isolates being MDR. Moreover, four isolates were carbapenem resistant with resistance to imipenem or meropenem. Among eight quinolone resistant <jats:italic>C. freundii<\/jats:italic>, all had a mutation in codon 59 (Thr59Ile) in quinolone resistance determining region of the <jats:italic>gyrA<\/jats:italic> gene. Only a small proportion of the isolates were found to be highly cytotoxic and adhesive with no correlation to sample sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There was a diverse range of <jats:italic>Citrobacter<\/jats:italic> isolates causing extraintestinal infections and a high prevalence of MDR.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.737636","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T05:27:35Z","timestamp":1630646855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":49,"title":["Antimicrobial Resistance and Molecular Characterization of Citrobacter spp. Causing Extraintestinal Infections"],"prefix":"10.3389","volume":"11","author":[{"given":"Liyun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiting","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.1093\/jac\/dkx325","article-title":"Carbapenem-Resistant Citrobacter Spp. Isolated in Spain From 2013 to 2015 Produced a Variety of Carbapenemases Including VIM-1, OXA-48, KPC-2, NDM-1 and VIM-2","volume":"72","author":"Arana","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e33054","DOI":"10.1371\/journal.pone.0033054","article-title":"Isolation and Characterization of Cytotoxic, Aggregative Citrobacter Freundii","volume":"7","author":"Bai","year":"2012","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.7150\/ijms.6251","article-title":"Citrobacter Peritoneal Dialysis Peritonitis: Rare Occurrence With Poor Outcomes","volume":"10","author":"Chao","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B4","article-title":"Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement","year":"2016","journal-title":"CLSI Document M100-S26"},{"key":"B5","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1592\/phco.27.2.191","article-title":"Predictors of in-Hospital Mortality for Bloodstream Infections Caused by Enterobacter Species or Citrobacter Freundii","volume":"27","author":"Deal","year":"2007","journal-title":"Pharmacotherapy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.meegid.2018.10.020","article-title":"Characterization of a Multidrug Resistant Citrobacter Amalonaticus Clinical Isolate Harboring Bla(NDM-1) and Mcr-1.5 Genes","volume":"67","author":"Faccone","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-87","article-title":"PHYLOViZ: Phylogenetic Inference and Data Visualization for Sequence Based Typing Methods","volume":"13","author":"Francisco","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e714","DOI":"10.1016\/j.ijid.2013.02.007","article-title":"Outbreak of Citrobacter Freundii Carrying VIM-1 in an Italian Hospital, Identified During the Carbapenemases Screening Actions, June 2012","volume":"17","author":"Gaibani","year":"2013","journal-title":"Int. J. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1093\/jac\/dkaa279","article-title":"Arrival of the Rare Carbapenemase OXA-204 in Canada Causing a Multispecies Outbreak Over 3\u2009Years","volume":"75","author":"Gobeille Par\u00e9","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.1093\/jac\/dkw289","article-title":"Use of WGS Data for Investigation of a Long-Term NDM-1-Producing Citrobacter Freundii Outbreak and Secondary In Vivo Spread of blaNDM-1 to Escherichia Coli, Klebsiella Pneumoniae and Klebsiella Oxytoca","volume":"71","author":"Hammerum","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jiac.2016.07.003","article-title":"Bacteremia Due to Citrobacter Braakii: A Case Report and Literature Review","volume":"22","author":"Hirai","year":"2016","journal-title":"J. Infect. Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/ajcp\/70.1.37","article-title":"Clinical Significance of Citrobacter Isolates","volume":"70","author":"Hodges","year":"1978","journal-title":"Am. J. Clin. Pathol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"166","DOI":"10.4103\/0300-1652.104389","article-title":"Prevalence and Pattern of Bacteria and Intestinal Parasites Among Food Handlers in the Federal Capital Territory of Nigeria","volume":"53","author":"Ifeadike","year":"2012","journal-title":"Niger. Med. J."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.PLAS-0006-2013","article-title":"Plasmid Mediated Quinolone Resistance","volume":"2","author":"Jacoby","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1093\/jac\/dkr283","article-title":"High Prevalence of Extended-Spectrum \u03b2-Lactamases and Qnr Determinants in Citrobacter Species From Japan: Dissemination of CTX-M-2","volume":"66","author":"Kanamori","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.burns.2007.12.008","article-title":"Profile of Microorganisms and Antimicrobial Resistance at a Tertiary Care Referral Burn Centre in Iran: Emergence of Citrobacter Freundii as a Common Microorganism","volume":"34","author":"Khorasani","year":"2008","journal-title":"Burns"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2013-008714","article-title":"Multidrug Resistant Citrobacter: An Unusual Cause of Liver Abscess","volume":"2013","author":"Kumar","year":"2013","journal-title":"BMJ Case Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis Across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.jhin.2010.06.006","article-title":"Bacteraemia Caused by Non-Freundii, Non-Koseri Citrobacter Species in Taiwan","volume":"76","author":"Lai","year":"2010","journal-title":"J. Hosp. Infect."},{"key":"B20","doi-asserted-by":"publisher","first-page":"837","DOI":"10.12659\/pjr.903276","article-title":"Multiple Brain Abscesses Caused by Citrobacter Koseri in a Preterm Neonate - Case Report","volume":"82","author":"Lechowicz","year":"2017","journal-title":"Pol. J. Radiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jmii.2013.08.010","article-title":"Risk Factors of Community-Onset Urinary Tract Infections Caused by Plasmid-Mediated AmpC \u03b2-Lactamase-Producing Enterobacteriaceae","volume":"48","author":"Lee","year":"2015","journal-title":"J.\u00a0Microbiol. Immunol. Infect."},{"key":"B22","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12879-016-1495-1","article-title":"High Prevalence of Multidrug Resistant Enterobacteriaceae Isolated From Outpatient Urine Samples But Not the Hospital Environment in Bo, Sierra Leone","volume":"16","author":"Leski","year":"2016","journal-title":"BMC Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.meegid.2015.07.011","article-title":"Characterization of Chromosomal qnrB and ampC alleles in Citrobacter freundii Isolates From Different Origins","volume":"35","author":"Liao","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00233","article-title":"Genetic Diversity, Multidrug Resistance, and Virulence of Citrobacter Freundii From Diarrheal Patients and Healthy Individuals","volume":"8","author":"Liu","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01357","article-title":"Antimicrobial Resistance and Cytotoxicity of Citrobacter Spp. In Maanshan Anhui Province, China","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3390\/pathogens9030195","article-title":"Lineage, Antimicrobial Resistance and Virulence of Citrobacter Spp","volume":"9","author":"Liu","year":"2020","journal-title":"Pathogens"},{"key":"B27","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.jmii.2016.08.016","article-title":"Citrobacter Freundii Bacteremia: Risk Factors of Mortality and Prevalence of Resistance Genes","volume":"51","author":"Liu","year":"2018","journal-title":"J.\u00a0Microbiol. Immunol. Infect."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00248-020-01645-z","article-title":"Population Structure and Multidrug Resistance of Non-O1\/Non-O139 Vibrio Cholerae in Freshwater Rivers in Zhejiang, China","author":"Luo","year":"2021","journal-title":"Microb. Ecol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1590\/s1517-838220120004000010","article-title":"Mutations in the Quinolone Resistance-Determining Regions of gyrA and parC in Enterobacteriaceae Isolates From Brazil","volume":"43","author":"Minarini","year":"2012","journal-title":"Braz. J. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jinf.2006.01.015","article-title":"Citrobacter Infections in a Tertiary Care Hospital in Northern India","volume":"54","author":"Mohanty","year":"2007","journal-title":"J. Infect."},{"key":"B31","first-page":"181","article-title":"A Small Outbreak of Third Generation Cephem-Resistant Citrobacter Freundii Infection on a Surgical Ward","volume":"57","author":"Nada","year":"2004","journal-title":"Jpn. J. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.2174\/1871526516666161005155847","article-title":"Citrobacter Braakii Bacteremia: Case Report and Review of the Literature","volume":"17","author":"Oyeka","year":"2017","journal-title":"Infect. Disord. Drug Targets"},{"key":"B33","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1093\/jac\/dkm266","article-title":"Prevalence and Diversity of qnr Alleles in AmpC-Producing Enterobacter cloacae, Enterobacter Aerogenes, Citrobacter Freundii and Serratia Marcescens: A Multicentre Study from Korea","volume":"60","author":"Park","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"5694","DOI":"10.1073\/pnas.1322678111","article-title":"Global Dissemination of a Multidrug Resistant Escherichia Coli Clone","volume":"111","author":"Petty","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B35","doi-asserted-by":"publisher","first-page":"6331","DOI":"10.1128\/aac.03168-14","article-title":"First Description of a blaVIM-2-Carrying Citrobacter Freundii Isolate in Spain","volume":"58","author":"Porres-Osante","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.ijantimicag.2008.05.008","article-title":"First Identification of VIM-1-Producing Citrobacter Freundii in Greece","volume":"32","author":"Protonotariou","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab209","article-title":"Three Clusters of Carbapenemase-Producing Citrobacter Freundii in Finland 2016-20","author":"R\u00e4is\u00e4nen","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"B38","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3390\/pathogens9020089","article-title":"Pathogenomic Analysis of a Novel Extensively Drug-Resistant Citrobacter Freundii Isolate Carrying a Bla(NDM-1) Carbapenemase in South Africa","volume":"9","author":"Ramsamy","year":"2020","journal-title":"Pathogens"},{"key":"B39","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.idcr.2017.09.005","article-title":"Strongyloides Hyperinfection Syndrome Causing Fatal Meningitis and Septicemia by Citrobacter Koseri","volume":"10","author":"Reyes","year":"2017","journal-title":"IDCases"},{"key":"B40","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s10096-008-0598-z","article-title":"Citrobacter Infections in a General Hospital: Characteristics and Outcomes","volume":"28","author":"Samonis","year":"2009","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jgar.2016.09.010","article-title":"Genetically Unrelated Multidrug- and Carbapenem-Resistant Citrobacter Freundii Detected in Outpatients Admitted to a Portuguese Hospital","volume":"8","author":"Santos","year":"2017","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00276","article-title":"Plasmid-Mediated Transmission of KPC-2 Carbapenemase in Enterobacteriaceae in Critically Ill Patients","volume":"10","author":"Schweizer","year":"2019","journal-title":"Front. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"137","DOI":"10.4314\/ejhs.v20i3.69442","article-title":"Microbial Flora and Food Borne Pathogens on Minced Meat and Their Susceptibility to Antimicrobial Agents","volume":"20","author":"Tassew","year":"2010","journal-title":"Ethiop. J. Health Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"bcr1020114941","DOI":"10.1136\/bcr.10.2011.4941","article-title":"Sepsis, Meningitis and Cerebral Abscesses Caused by Citrobacter Koseri","volume":"2012","author":"Vaz Marecos","year":"2012","journal-title":"BMJ Case Rep."},{"key":"B45","first-page":"258","article-title":"Comparison of Antimicrobial Susceptibility of Citrobacter Freundii Isolates in Two Different Time Periods","volume":"33","author":"Wang","year":"2000","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1128\/aac.42.10.2661","article-title":"gyrA Mutations Associated With Fluoroquinolone Resistance in Eight Species of Enterobacteriaceae","volume":"42","author":"Weigel","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"B47","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1080\/00365540600868388","article-title":"First Detection of a VIM-1 Metallo-Beta-Lactamase in a Carbapenem-Resistant Citrobacter Freundii Clinical Isolate in an Acute Hospital in Germany","volume":"39","author":"Weile","year":"2007","journal-title":"Scand. J. Infect. Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"10653","DOI":"10.1038\/s41598-018-28879-9","article-title":"Multidrug-Resistant Citrobacter Freundii ST139 Co-Producing NDM-1 and CMY-152 From China","volume":"8","author":"Yang","year":"2018","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1264\/jsme2.ME11308","article-title":"High Prevalence of qnr and aac(6\u2019)-Ib-cr Genes in Both Water-Borne Environmental Bacteria and Clinical Isolates of Citrobacter freundii in China","volume":"27","author":"Zhang","year":"2012","journal-title":"Microb. Environ."},{"key":"B50","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1099\/jmm.0.47576-0","article-title":"High-Level Carbapenem Resistance in a Citrobacter Freundii Clinical Isolate Is Due to a Combination of KPC-2 Production and Decreased Porin Expression","volume":"57","author":"Zhang","year":"2008","journal-title":"J. Med. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.737636\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T05:27:40Z","timestamp":1630646860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.737636\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":50,"alternative-id":["10.3389\/fcimb.2021.737636"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.737636","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]},"article-number":"737636"}}