{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:45Z","timestamp":1787026305229,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      Carbapenem-resistant\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study investigated the\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      activity of meropenem\/vaborbactam (MEV) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopedic oncologic surgery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing identified the isolates as ST101 and ST307, harboring resistance determinants including\n                      <jats:italic>\n                        bla\n                        <jats:sub>KPC-3<\/jats:sub>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        bla\n                        <jats:sub>OXA-1<\/jats:sub>\n                      <\/jats:italic>\n                      , distributed across IncFII and IncFIB plasmid replicons. Both isolates exhibited extensive resistance to \u03b2-lactams, aminoglycosides, and fluoroquinolones but remained susceptible to MEV. Phenotypic assays revealed enhanced biofilm formation and metabolic activity compared to the reference strain Kp ATCC 13883 in the absence of hypervirulence-associated genes. MEV demonstrated bactericidal activity against both planktonic and biofilm-associated cells, with minimum bactericidal concentration (MBC\n                      <jats:sub>90<\/jats:sub>\n                      ) and minimum biofilm eradication concentration (MBEC\n                      <jats:sub>90<\/jats:sub>\n                      ) values of 0.5\/8 \u03bcg\/ml for CRKP ST101, 0.12\/8 \u03bcg\/ml for CRKP ST307, and 0.25\/8 \u03bcg\/ml for the Kp ATCC 13883 strain. In the\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      infection model, MEV significantly improved larval survival following the CRKP challenge.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that MEV exhibits activity against planktonic and biofilm-associated CRKP cells and highlight the need for further investigation in managing catheter-related bloodstream infections caused by multidrug-resistant\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1616353","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T06:08:13Z","timestamp":1753942093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Meropenem\/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections"],"prefix":"10.3389","volume":"15","author":[{"given":"Francesca","family":"Sivori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Francalancia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Truglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cavallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelina","family":"Pronesti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Fabrizio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Celesti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cazzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Furzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvia","family":"Pimpinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enea Gino","family":"Di Domenico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.ijantimicag.2015.07.014","article-title":"Evaluation of antibiotic efficacy against infections caused by planktonic or biofilm cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae in Galleria mellonella","volume":"46","author":"Benthall","year":"2015","journal-title":"Int. J. Antimicrobial. Agents"},{"key":"B3","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1093\/jac\/dkae450","article-title":"In vitro activity and genomic characterization of KPC-producing Klebsiella pneumoniae clinical blood culture isolates resistant to ceftazidime\/avibactam, meropenem\/vaborbactam, imipenem\/relebactam: an Italian nationwide multicentre observational study, (2022\u201323)","volume":"80","author":"Bianco","year":"2025","journal-title":"J. Antimicrobial. Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"W46","DOI":"10.1093\/nar\/gkad344","article-title":"antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation","volume":"51","author":"Blin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0132936","DOI":"10.1371\/journal.pone.0132936","article-title":"An Update of the Evolving Epidemic of blaKPC Carrying Klebsiella pneumoniae in Sicily, Italy 2014: emergence of multiple non-ST258 clones","volume":"10","author":"Bonura","year":"2015","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1111\/apm.12666","article-title":"Carbapenemases-producing Klebsiella pneumoniae in hospitals of two regions of Southern Italy","volume":"125","author":"Calia","year":"2017","journal-title":"APMIS"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using plasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.561741","article-title":"Biofilm production by carbapenem-resistant klebsiella pneumoniae significantly increases the risk of death in oncological patients","volume":"10","author":"Di Domenico","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e00550","DOI":"10.1128\/Spectrum.00550-21","article-title":"The impact of bacterial biofilms on end-organ disease and mortality in patients with hematologic Malignancies developing a bloodstream infection","volume":"9","author":"Di Domenico","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10071259","article-title":"The current knowledge on the pathogenesis of tissue and medical device-related biofilm infections","volume":"10","author":"Di Domenico","year":"2022","journal-title":"Microorganisms"},{"key":"B11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/14787210.2024.2305854","article-title":"Carbapenem-resistant Klebsiella pneumoniae : the role of plasmids in emergence, dissemination, and evolution of a major clinical challenge","volume":"22","author":"Di Pilato","year":"2024","journal-title":"Expert Rev. Anti-infective Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"Ewels","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1432883","article-title":"Efficacy of sodium hypochlorite in overcoming antimicrobial resistance and eradicating biofilms in clinical pathogens from pressure ulcers","volume":"15","author":"Fabrizio","year":"2024","journal-title":"Front. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1186\/s12879-019-4565-3","article-title":"Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy","volume":"19","author":"Fasciana","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10050536","article-title":"Epidemiology of meropenem\/vaborbactam resistance in KPC-producing klebsiella pneumoniae causing bloodstream infections in northern Italy","volume":"10","author":"Gaibani","year":"2021","journal-title":"Antibiotics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1093\/bioinformatics\/btv271","article-title":"kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome","volume":"31","author":"Gardner","year":"2015","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"20489","DOI":"10.2807\/ese.18.22.20489-en","article-title":"Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011","volume":"18","author":"Giani","year":"2013","journal-title":"Euro Surveill"},{"key":"B19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s10096-024-04986-6","article-title":"Meropenem-vaborbactam as intrathecal-sparing therapy for the treatment of carbapenem-resistant K. pneumoniae shunt-related ventriculitis: two case reports and review of the literature","volume":"44","author":"Giuliano","year":"2025","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/apm.12665","article-title":"Central venous catheters and biofilms: where do we stand in 2017","volume":"125","author":"Gominet","year":"2017","journal-title":"APMIS"},{"key":"B21","doi-asserted-by":"publisher","first-page":"W484","DOI":"10.1093\/nar\/gkad326","article-title":"Proksee: in-depth characterization and visualization of bacterial genomes","volume":"51","author":"Grant","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e02215","DOI":"10.1128\/spectrum.02215-24","article-title":"Virulence profile of carbapenem-resistant Klebsiella pneumoniae strains by an in vivo model of Galleria mellonella","author":"Guembe","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1564010","article-title":"Corrigendum: Klebsiella pneumoniae biofilms and their role in disease pathogenesis","volume":"15","author":"Guerra","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1186\/s13104-017-2757-8","article-title":"Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials","volume":"10","author":"Ignasiak","year":"2017","journal-title":"BMC Res. Notes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/phar.2092","article-title":"Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae","volume":"38","author":"Jorgensen","year":"2018","journal-title":"Pharmacotherapy"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000800","article-title":"Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex","volume":"8","author":"Lam","year":"2022","journal-title":"Microbial. Genomics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4188","DOI":"10.1038\/s41467-021-24448-3","article-title":"A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex","volume":"12","author":"Lam","year":"2021","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1007\/s15010-023-02055-2","article-title":"Continuous infusion of meropenem\u2013vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance","volume":"51","author":"Larcher","year":"2023","journal-title":"Infection"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0251010","article-title":"Changing epidemiology of catheter-related bloodstream infections in neutropenic oncohematological patients","volume":"16","author":"Lendak","year":"2021","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"W78","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive Tree of Life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool","volume":"52","author":"Letunic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12941-020-00366-y","article-title":"Emerging high-risk ST101 and ST307 carbapenem-resistant Klebsiella pneumoniae clones from bloodstream infections in Southern Italy","volume":"19","author":"Loconsole","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s13059-016-0997-x","article-title":"Mash: fast genome and metagenome distance estimation using MinHash","volume":"17","author":"Ondov","year":"2016","journal-title":"Genome Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: going on the offense with a strong defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e00190","DOI":"10.1128\/mSystems.00190-20","article-title":"Bactopia: a flexible pipeline for complete analysis of bacterial genomes","volume":"5","author":"Petit","year":"2020","journal-title":"mSystems"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1016\/j.scib.2023.09.040","article-title":"Superbugs\u201d with hypervirulence and carbapenem resistance in Klebsiella pneumoniae: the rise of such emerging nosocomial pathogens in China","volume":"68","author":"Pu","year":"2023","journal-title":"Sci. Bull."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/S0140-6736(21)00351-2","article-title":"Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)\u2013non-inferiority (peripheral arterial catheter) trial","volume":"397","author":"Rickard","year":"2021","journal-title":"Lancet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioflm.2024.100222","article-title":"Staphylococcus aureus colonizing the skin microbiota of adults with severe atopic dermatitis exhibits genomic diversity and convergence in biofilm traits","volume":"8","author":"Sivori","year":"2024","journal-title":"Biofilm"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-024-04758-2","article-title":"Real-world experience with meropenem\/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae","author":"Tiseo","year":"2024","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae273","article-title":"Outcomes and predictors of mortality in patients with KPC-kp infections treated with meropenem vaborbactam: an observational multicenter study","volume":"11","author":"Tumbarello","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1111\/jam.13533","article-title":"Biofilm formation and antibiotic resistance in Klebsiella pneumoniae urinary strains","volume":"123","author":"Vuotto","year":"2017","journal-title":"J. Appl. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1099\/jmm.0.037523-0","article-title":"Acinetobacter baumannii virulence is enhanced in Galleria mellonella following biofilm adaptation","volume":"61","author":"Wand","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009802","article-title":"Polypolish: Short-read polishing of long-read bacterial genome assemblies","volume":"18","author":"Wick","year":"2022","journal-title":"PloS Comput. Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/s41579-019-0315-1","article-title":"Population genomics of Klebsiella pneumoniae","volume":"18","author":"Wyres","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1221428","article-title":"Convergence of plasmid-mediated Colistin and Tigecycline resistance in Klebsiella pneumoniae","volume":"14","author":"Zhao","year":"2024","journal-title":"Front. Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/j.1574-695X.2012.00938.x","article-title":"Pathogenesis and treatment concepts of orthopaedic biofilm infections","volume":"65","author":"Zimmerli","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1616353\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T06:08:13Z","timestamp":1753942093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1616353\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":46,"alternative-id":["10.3389\/fcimb.2025.1616353"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1616353","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"article-number":"1616353"}}