{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:35:59Z","timestamp":1780385759420,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type \u03b2-lactamase, and extended spectrum \u03b2-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin\/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffmannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin\/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57\/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25\u20135.06), received ventilator support (OR: 5.54, 95% CI: 2.25\u201312.03), steroid exposure (OR: 3.88, 95% CI: 1.91\u20137.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10\u20134.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions.<\/jats:p>","DOI":"10.3390\/pathogens11020151","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T21:07:11Z","timestamp":1643144831000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem-Nonsusceptible Enterobacter cloacae Complex Infections in a Taiwan University Hospital"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-5966","authenticated-orcid":false,"given":"Chao-Ju","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"},{"name":"College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7423-6783","authenticated-orcid":false,"given":"Po-Liang","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Huei","family":"Jian","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Ling","family":"Fu","sequence":"additional","affiliation":[{"name":"M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Laboratory Medicine, Kaohsiung Municipal Feng-Shan Hospital (Under the Management of Chang Gung Memorail Hospital), Kaohsiung 83062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.2217\/fmb.12.61","article-title":"Enterobacter cloacae complex: Clinical impact and emerging antibiotic resistance","volume":"7","author":"Mezzatesta","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1574-6968.2011.02479.x","article-title":"A dual approach employing MALDI-TOF MS and real-time PCR for fast species identification within the Enterobacter cloacae complex","volume":"328","author":"Pavlovic","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liu, S., Fang, R., Zhang, Y., Chen, L., Huang, N., Yu, K., Zhou, C., Cao, J., and Zhou, T. (2021). Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02250-x"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jean, S.S., Lee, Y.L., Liu, P.Y., Lu, M.C., Ko, W.C., and Hsueh, P.R. (2021). Multicenter surveillance of antimicrobial susceptibilities and resistance mechanisms among Enterobacterales species and non-fermenting Gram-negative bacteria from different infection sources in Taiwan from 2016 to 2018. J. Microbiol. Immunol. Infect.","DOI":"10.1016\/j.jmii.2021.07.015"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.drup.2016.09.002","article-title":"The rapid spread of carbapenem-resistant Enterobacteriaceae","volume":"29","author":"Potter","year":"2016","journal-title":"Drug Resist. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00002-19","DOI":"10.1128\/CMR.00002-19","article-title":"Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance","volume":"32","author":"Lavigne","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fmicb.2019.00044","article-title":"Multidrug-Resistant Enterobacter cloacae Complex Emerging as a Global, Diversifying Threat","volume":"10","author":"Annavajhala","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00661-21","DOI":"10.1128\/Spectrum.00661-21","article-title":"Revisiting Species Identification within the Enterobacter cloacae Complex by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry","volume":"9","author":"Godmer","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Singh, N.K., Bezdan, D., Checinska Sielaff, A., Wheeler, K., Mason, C.E., and Venkateswaran, K. (2018). Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains. BMC Microbiol., 18.","DOI":"10.1186\/s12866-018-1325-2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00527-20","DOI":"10.1128\/mSystems.00527-20","article-title":"Precise Species Identification for Enterobacter: A Genome Sequence-Based Study with Reporting of Two Novel Species, Enterobacter quasiroggenkampii sp. nov. and Enterobacter quasimori sp. nov","volume":"5","author":"Wu","year":"2020","journal-title":"mSystems"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00181-19","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in eskape pathogens","volume":"33","author":"Forde","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.3201\/eid2406.171648","article-title":"Genomic Epidemiology of Global Carbapenemase-Producing Enterobacter spp., 2008\u20132014","volume":"24","author":"Peirano","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","first-page":"392","article-title":"Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment","volume":"6","author":"Pages","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3201\/eid2305.162034","article-title":"Carbapenem-Resistant Enterobacter cloacae in Patients from the US Veterans Health Administration, 2006\u20132015","volume":"23","author":"Wilson","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e02091-17","DOI":"10.1128\/AAC.02091-17","article-title":"Molecular Characterization of IMP-1-Producing Enterobacter cloacae Complex Isolates in Tokyo","volume":"62","author":"Aoki","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.3389\/fmicb.2018.02888","article-title":"Carbapenem-Resistant Enterobacteriaceae Infections: Taiwan Aspects","volume":"9","author":"Jean","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, J., Tian, S., Nian, H., Wang, R., Li, F., Jiang, N., and Chu, Y. (2021). Carbapenem-resistant Enterobacter cloacae complex in a tertiary Hospital in Northeast China, 2010-2019. BMC. Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06250-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"627","DOI":"10.2147\/IDR.S194482","article-title":"Susceptibility rates of clinically important bacteria collected from intensive care units against colistin, carbapenems, and other comparative agents: Results from Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)","volume":"12","author":"Lai","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Suay-Garc\u00eda, B., and P\u00e9rez-Gracia, M.T. (2019). Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibioticcs, 8.","DOI":"10.3390\/antibiotics8030122"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jhin.2013.06.010","article-title":"Outbreak of ertapenem-resistant Enterobacter cloacae urinary tract infections due to a contaminated ureteroscope","volume":"85","author":"Chang","year":"2013","journal-title":"J. Hosp. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/mdr.2015.0311","article-title":"A Snapshot of Co-Resistance to Carbapenems and Tigecycline in Clinical Isolates of Enterobacter cloacae","volume":"23","author":"Huang","year":"2017","journal-title":"Microb. Drug Resist."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/jac\/dkw398","article-title":"Distribution of ESBLs, AmpC \u03b2-lactamases and carbapenemases among Enterobacteriaceae isolates causing intra-abdominal and urinary tract infections in the Asia-Pacific region during 2008\u20132014: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART)","volume":"72","author":"Jean","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, J.T., Wu, U.I., Lauderdale, T.L., Chen, M.C., Li, S.Y., Hsu, L.Y., and Chang, S.C. (2015). Carbapenem-nonsusceptible Enterobacteriaceae in Taiwan. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121668"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1128\/JCM.01263-11","article-title":"Characterization of ertapenem-resistant Enterobacter cloacae in a Taiwanese university hospital","volume":"50","author":"Yang","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1093\/cid\/cix113","article-title":"Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore","volume":"64","author":"Marimuthu","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13756-019-0578-3","article-title":"Molecular epidemiological analysis and risk factors for acquisition of carbapenemase-producing Enterobacter cloacae complex in a Japanese university hospital","volume":"8","author":"Tetsuka","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1093\/jac\/dky317","article-title":"Stability and low induction propensity of cefiderocol against chromosomal AmpC \u03b2-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae","volume":"73","author":"Ito","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e02349-16","DOI":"10.1128\/AAC.02349-16","article-title":"Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States","volume":"61","author":"Satlin","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.2147\/IDR.S244357","article-title":"Evaluation of Resistance Mechanisms in Carbapenem-Resistant Enterobacteriaceae","volume":"13","author":"Alizadeh","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.2147\/IDR.S327595","article-title":"Molecular mechanisms and epidemiology of carbapenem-resistant Enterobacter cloacae complex isolated from chinese patients during 2004\u20132018","volume":"14","author":"Liu","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.3389\/fmicb.2017.02343","article-title":"Molecular Characteristics of First IMP-4-Producing Enterobacter cloacae Sequence Type 74 and 194 in Korea","volume":"8","author":"Lee","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1128\/JCM.02458-09","article-title":"Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility","volume":"48","author":"Endimiani","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8468","DOI":"10.1038\/s41598-018-26691-z","article-title":"Carbapenem Nonsusceptible Klebsiella pneumoniae in Taiwan: Dissemination and Increasing Resistance of Carbapenemase Producers During 2012\u20132015","volume":"8","author":"Chiu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"715821","DOI":"10.3389\/fcimb.2021.715821","article-title":"Using Molecular Diagnostics to Develop Therapeutic Strategies for Carbapenem-Resistant Gram-Negative Infections","volume":"11","author":"Tenover","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1128\/JCM.02264-16","article-title":"Implementation of Rapid Molecular Infectious Disease Diagnostics: The Role of Diagnostic and Antimicrobial Stewardship","volume":"55","author":"Messacar","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/cid\/ciw741","article-title":"Comparing the Outcomes of Patients with Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia","volume":"64","author":"Tamma","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"716324","DOI":"10.3389\/fphar.2021.716324","article-title":"Clinical and Microbiological Characterization of Carbapenem-Resistant Enterobacteriales: A Prospective Cohort Study","volume":"12","author":"Lin","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_38","unstructured":"CLSI (2021). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [31st ed.]. CLSI Supplement M100."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.1128\/AEM.69.9.5306-5318.2003","article-title":"Population genetics of the nomenspecies Enterobacter cloacae","volume":"69","author":"Hoffmann","year":"2003","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1086\/501950","article-title":"Comparison of pulsed-field gel electrophoresis and amplified fragment-length polymorphism for epidemiological investigations of common nosocomial pathogens","volume":"22","author":"Gerrits","year":"2001","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1128\/jcm.33.9.2233-2239.1995","article-title":"Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: Criteria for bacterial strain typing","volume":"33","author":"Tenover","year":"1995","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chiu, S.K., Wu, T.L., Chuang, Y.C., Lin, J.C., Fung, C.P., Lu, P.L., Wang, J.T., Wang, L.S., Siu, L.K., and Yeh, K.M. (2013). National surveillance study on carbapenem non-susceptible Klebsiella pneumoniae in Taiwan: The emergence and rapid dissemination of KPC-2 carbapenemase. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069428"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1128\/AAC.48.2.533-537.2004","article-title":"Epidemiology of conjugative plasmid-mediated AmpC \u03b2-lactamases in the United States","volume":"48","author":"Alvarez","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1128\/AAC.48.4.1249-1255.2004","article-title":"Dissemination of CTX-M-type \u03b2-lactamases among clinical isolates of Enterobacteriaceae in Paris, France","volume":"48","author":"Eckert","year":"2004","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:07:22Z","timestamp":1760134042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,25]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["pathogens11020151"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11020151","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,25]]}}}