{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:18:48Z","timestamp":1791566328169,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Carbapenem-resistant\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) infections pose a major clinical challenge due to multidrug resistance. This study evaluated the clinical features, antibiotic resistance mechanisms, virulence factors, and the potential therapeutic impact of berberine hydrochloride (a traditional Chinese medicine) in CRKP infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ninety-four CRKP isolates from bloodstream infections at the First Affiliated Hospital of Zhejiang Chinese Medical University were characterized for carbapenemase genes, antibiotic susceptibility, and virulence determinants. Clinical data were analyzed to identify risk factors for CRKP infection, and the\n                      <jats:italic>in vitro<\/jats:italic>\n                      antibacterial activity of berberine hydrochloride was assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most of the isolates (71.3%) were from the intensive care unit (ICU) patients. The\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC<\/jats:sub>\n                      gene was the predominant resistance mechanism (62.77%), while the virulence genes\n                      <jats:italic>uge<\/jats:italic>\n                      (93.62%) and\n                      <jats:italic>wabG<\/jats:italic>\n                      (92.55%) were highly prevalent. ICU admission, male sex, respiratory diseases, invasive procedures, prior use of third-generation cephalosporinase inhibitors, and absence of traditional Chinese medicine treatment were linked to poorer outcomes. Importantly, berberine hydrochloride inhibited CRKP growth\n                      <jats:italic>in vitro<\/jats:italic>\n                      , with a minimum inhibitory concentration (MIC) of 125 mg\/mL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals the multifaceted resistance and virulence profiles of CRKP in bloodstream infections and highlights the potential clinical value of berberine hydrochloride as an adjunctive therapeutic agent. These findings support further clinical investigations into incorporating traditional Chinese medicine to improve outcomes in patients with CRKP bloodstream infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1541704","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T01:52:16Z","timestamp":1741312336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Characterization of carbapenem-resistant Klebsiella pneumoniae in bloodstream infections: antibiotic resistance, virulence, and treatment strategies"],"prefix":"10.3389","volume":"15","author":[{"given":"Chenglin","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1089\/mdr.2018.0181","article-title":"First report of extended-spectrum betalactamase-producing klebsiella pneumoniae among fecal carriage in Iran: high diversity of clonal relatedness and virulence factor profiles","volume":"26","author":"Aghamohammad","year":"2020","journal-title":"Microb. Drug Resist."},{"key":"B2","first-page":"3","article-title":"Carbapenemase-producing Enterobacteriaceae in animals and methodologies for their detection","volume":"84","author":"Anderson","year":"2020","journal-title":"Can. J. Vet. Res."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00432-19","article-title":"Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC","volume":"63","author":"Barnes","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1086\/675611","article-title":"Statewide surveillance of carbapenem-resistant enterobacteriaceae in Michigan","volume":"35","author":"Brennan","year":"2014","journal-title":"Infect. Control Hosp Epidemiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/aac.01009-09","article-title":"Updated functional classification of beta-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1128\/aac.39.6.1211","article-title":"A functional classification scheme for beta-lactamases and its correlation with molecular structure","volume":"39","author":"Bush","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"867","DOI":"10.18388\/abp.2015_1148","article-title":"Klebsiella pneumoniae: characteristics of carbapenem resistance and virulence factors","volume":"62","author":"Candan","year":"2015","journal-title":"Acta Biochim. Pol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3390\/antibiotics9100719","article-title":"Relationship between virulence and resistance among gram-negative bacteria","volume":"9","author":"Cepas","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/s1473-3099(17)30517-0","article-title":"Convergence of carbapenem-resistance and hypervirulence in Klebsiella pneumoniae","volume":"18","author":"Chen","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B10","unstructured":"Changes in antimicrobial resistance of pathogenic bacteria from blood specimens in China from 2014 to 2019 [in Chinese]\n          \n          124\n          133\n          \n          10.12138\/j.issn.1671-9638.20216173\n          Chinese J. Infect. Control\n          20\n          2021"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/srep24748","article-title":"Role of berberine in the treatment of methicillin-resistant staphylococcus aureus infections","volume":"6","author":"Chu","year":"2016","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24743","article-title":"The making of hypervirulent Klebsiella pneumoniae","volume":"36","author":"Dai","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112551","article-title":"Epitopes in the capsular polysaccharide and the porin OmpK36 receptors are required for bacteriophage infection of Klebsiella pneumoniae","volume":"42","author":"Dunstan","year":"2023","journal-title":"Cell Rep."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1003783","article-title":"Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae","volume":"13","author":"Han","year":"2022","journal-title":"Front. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"671","DOI":"10.16718\/j.1009-7708.2020.06.015","article-title":"Consensus statement on laboratory detection and clinical report of carbapenemases among Enterobacterales","volume":"20","author":"Hua","year":"2020","journal-title":"Chin. J. Infect. Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jhin.2012.10.012","article-title":"Impact of carbapenem resistance on the outcome of patients\u2019 hospital-acquired bacteraemia caused by Klebsiella pneumoniae","volume":"83","author":"Hussein","year":"2013","journal-title":"J. Hosp Infect."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007338","article-title":"Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic clearance by modulating cell death machinery","volume":"14","author":"Jondle","year":"2018","journal-title":"PloS Pathog."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1038\/s41598-023-31086-w","article-title":"Virulence analysis and antibiotic resistance of Klebsiella pneumoniae isolates from hospitalised patients in Poland","volume":"13","author":"Kot","year":"2023","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.jgar.2019.09.006","article-title":"Risk factors for carbapenem-resistant Klebsiella pneumoniae infection: A meta-analysis","volume":"21","author":"Li","year":"2020","journal-title":"J. Global Antimicrobial Resistance"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.660431","article-title":"A potential combination therapy of berberine hydrochloride with antibiotics against multidrug-resistant acinetobacter baumannii","volume":"11","author":"Li","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2024.106774","article-title":"Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa","volume":"193","author":"Liu","year":"2024","journal-title":"Microbial Pathogenesis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.2147\/idr.S276975","article-title":"Antibiogram and genetic characterization of carbapenem-resistant gram-negative pathogens incriminated in healthcare-associated infections","volume":"13","author":"Makharita","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B23","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13756-019-0477-7","article-title":"Evaluation of co-transfer of plasmid-mediated fluoroquinolone resistance genes and bla(NDM) gene in Enterobacteriaceae causing neonatal septicaemia","volume":"8","author":"Mitra","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1093\/jac\/dkt487","article-title":"Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae. J","volume":"69","author":"Naparstek","year":"2014","journal-title":"Antimicrob. Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1128\/cmr.00001-07","article-title":"Carbapenemases: the versatile beta-lactamases","volume":"20","author":"Queenan","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"210","DOI":"10.4103\/ijmm.IJMM_19_157","article-title":"Characterisation of virulence genes associated with pathogenicity in Klebsiella pneumoniae","volume":"37","author":"Remya","year":"2019","journal-title":"Indian J. Med. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1017\/ice.2018.63","article-title":"Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae","volume":"39","author":"Scheuerman","year":"2018","journal-title":"Infect. Control Hosp Epidemiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/genes8010039","article-title":"The complex relationship between virulence and antibiotic resistance","volume":"8","author":"Schroeder","year":"2017","journal-title":"Genes (Basel)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/viru.22718","article-title":"Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed","volume":"4","author":"Shon","year":"2013","journal-title":"Virulence"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041505","article-title":"Functional characterization of a novel outer membrane porin KpnO, regulated by PhoBR two-component system in Klebsiella pneumoniae NTUH-K2044","volume":"7","author":"Srinivasan","year":"2012","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1276383","article-title":"The antibacterial activity of berberine against Cutibacterium acnes: its therapeutic potential in inflammatory acne","volume":"14","author":"Sun","year":"2023","journal-title":"Front. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"6278","DOI":"10.3390\/ijerph17176278","article-title":"The characteristic of virulence, biofilm and antibiotic resistance of klebsiella pneumoniae","volume":"17","author":"Wang","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"6583","DOI":"10.3390\/molecules19056583","article-title":"Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative staphylococcus strains in vitro","volume":"19","author":"Wojtyczka","year":"2014","journal-title":"Molecules"},{"key":"B34","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1080\/22221751.2022.2049458","article-title":"Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae in China","volume":"11","author":"Yang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"B35","doi-asserted-by":"publisher","first-page":"388","DOI":"10.13350\/j.cjpb.160502","article-title":"Analysis of the bacteriostatic action of Scutelaria baicalensis on Klebsiela pneumoniae and the mechanisms of that action","volume":"11","author":"Yin","year":"2016","journal-title":"J. Pathogen Bioogy"},{"key":"B36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.2147\/idr.S223243","article-title":"Risk factors for carbapenem-resistant klebsiella pneumoniae bloodstream infections and outcomes","volume":"13","author":"Yuan","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.2147\/idr.S298530","article-title":"Risk factors for and clinical outcomes of carbapenem-resistant klebsiella pneumoniae nosocomial infections: A retrospective study in a tertiary hospital in Beijing, China","volume":"14","author":"Zhang","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"B38","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s12879-018-3160-3","article-title":"Risk factors for carbapenem-resistant K. pneumoniae bloodstream infection and predictors of mortality in Chinese paediatric patients","volume":"18","author":"Zhang","year":"2018","journal-title":"BMC Infect. Dis."},{"key":"B39","first-page":"303","article-title":"Influence of forsythoside B on efflux pump activity of Klebsiella pneumoniae","volume":"32","author":"Zhong Haiqin","year":"2013","journal-title":"Chin. J. New Drugs Clin. Rem"},{"key":"B40","doi-asserted-by":"publisher","first-page":"7313","DOI":"10.2147\/idr.S431256","article-title":"Potentiation and mechanism of berberine as an antibiotic adjuvant against multidrug-resistant bacteria","volume":"16","author":"Zhou","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"B41","doi-asserted-by":"publisher","first-page":"6671","DOI":"10.2147\/idr.S383010","article-title":"Antibiotic resistance, molecular characteristics and risk factors of carbapenem-resistant klebsiella pneumoniae in clinical isolates","volume":"15","author":"Zhu","year":"2022","journal-title":"Infect. Drug Resist."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1541704\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T01:52:22Z","timestamp":1741312342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1541704\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":41,"alternative-id":["10.3389\/fcimb.2025.1541704"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1541704","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,7]]},"article-number":"1541704"}}