Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections
IntroductionCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices.MethodsThis study investigated the in vitro and in vivo activity of meropenem/vaborbactam (MEV) aga...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1616353/full |
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| author | Francesca Sivori Massimo Francalancia Mauro Truglio Ilaria Cavallo Carmelina Pronesti Giorgia Fabrizio Ilaria Celesti Andrea Cazzani Lorenzo Furzi Fulvia Pimpinelli Enea Gino Di Domenico |
| author_facet | Francesca Sivori Massimo Francalancia Mauro Truglio Ilaria Cavallo Carmelina Pronesti Giorgia Fabrizio Ilaria Celesti Andrea Cazzani Lorenzo Furzi Fulvia Pimpinelli Enea Gino Di Domenico |
| author_sort | Francesca Sivori |
| collection | DOAJ |
| description | IntroductionCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices.MethodsThis study investigated the in vitro and in vivo activity of meropenem/vaborbactam (MEV) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopedic oncologic surgery.ResultsWhole-genome sequencing identified the isolates as ST101 and ST307, harboring resistance determinants including blaKPC-3 and blaOXA-1, distributed across IncFII and IncFIB plasmid replicons. Both isolates exhibited extensive resistance to β-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 (MBC90) and minimum biofilm eradication concentration (MBEC90) values of 0.5/8 μg/ml for CRKP ST101, 0.12/8 μg/ml for CRKP ST307, and 0.25/8 μg/ml for the Kp ATCC 13883 strain. In the Galleria mellonella infection model, MEV significantly improved larval survival following the CRKP challenge.DiscussionThese 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 K. pneumoniae. |
| format | Article |
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| issn | 2235-2988 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-ec2c808ff1fb47e29a68c39d009a9d192025-07-31T06:08:09ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.16163531616353Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infectionsFrancesca Sivori0Massimo Francalancia1Mauro Truglio2Ilaria Cavallo3Carmelina Pronesti4Giorgia Fabrizio5Ilaria Celesti6Andrea Cazzani7Lorenzo Furzi8Fulvia Pimpinelli9Enea Gino Di Domenico10Microbiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyHospital Infection Control Committee, Istituti Fisioterapici Ospitalieri (IFO), Rome, ItalyDepartment of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyMicrobiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, ItalyIntroductionCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices.MethodsThis study investigated the in vitro and in vivo activity of meropenem/vaborbactam (MEV) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopedic oncologic surgery.ResultsWhole-genome sequencing identified the isolates as ST101 and ST307, harboring resistance determinants including blaKPC-3 and blaOXA-1, distributed across IncFII and IncFIB plasmid replicons. Both isolates exhibited extensive resistance to β-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 (MBC90) and minimum biofilm eradication concentration (MBEC90) values of 0.5/8 μg/ml for CRKP ST101, 0.12/8 μg/ml for CRKP ST307, and 0.25/8 μg/ml for the Kp ATCC 13883 strain. In the Galleria mellonella infection model, MEV significantly improved larval survival following the CRKP challenge.DiscussionThese 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 K. pneumoniae.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1616353/fullcarbapenem-resistant Klebsiella pneumoniaemultidrug-resistant plasmidmeropenem/vaborbactamcatheter-related bloodstream infectionsbiofilm-associated infectionssurgical site infection |
| spellingShingle | Francesca Sivori Massimo Francalancia Mauro Truglio Ilaria Cavallo Carmelina Pronesti Giorgia Fabrizio Ilaria Celesti Andrea Cazzani Lorenzo Furzi Fulvia Pimpinelli Enea Gino Di Domenico Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections Frontiers in Cellular and Infection Microbiology carbapenem-resistant Klebsiella pneumoniae multidrug-resistant plasmid meropenem/vaborbactam catheter-related bloodstream infections biofilm-associated infections surgical site infection |
| title | Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections |
| title_full | Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections |
| title_fullStr | Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections |
| title_full_unstemmed | Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections |
| title_short | Meropenem/vaborbactam activity against carbapenem-resistant Klebsiella pneumoniae from catheter-related bloodstream infections |
| title_sort | meropenem vaborbactam activity against carbapenem resistant klebsiella pneumoniae from catheter related bloodstream infections |
| topic | carbapenem-resistant Klebsiella pneumoniae multidrug-resistant plasmid meropenem/vaborbactam catheter-related bloodstream infections biofilm-associated infections surgical site infection |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1616353/full |
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