Sivori Francesca, Francalancia Massimo, Truglio Mauro, Cavallo Ilaria, Pronesti Carmelina, Fabrizio Giorgia, Celesti Ilaria, Cazzani Andrea, Furzi Lorenzo, Pimpinelli Fulvia, Di Domenico Enea Gino
Microbiology and Virology, San Gallicano Dermatological Institute IRCCS, Rome, Italy.
Hospital Infection Control Committee, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.
Front Cell Infect Microbiol. 2025 Jul 31;15:1616353. doi: 10.3389/fcimb.2025.1616353. eCollection 2025.
Carbapenem-resistant (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices.
This study investigated the and activity of meropenem/vaborbactam (MEV) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopedic oncologic surgery.
Whole-genome sequencing identified the isolates as ST101 and ST307, harboring resistance determinants including and , 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 (MBC) and minimum biofilm eradication concentration (MBEC) 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 infection model, MEV significantly improved larval survival following the CRKP challenge.
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 .
耐碳青霉烯类肺炎克雷伯菌（CRKP）因其多重耐药性以及在植入式医疗器械上形成生物膜的能力，在肿瘤治疗环境中构成了重大威胁。
本研究调查了美罗培南/巴罗巴坦（MEV）对从接受骨科肿瘤手术患者的导管相关血流感染中分离出的两株CRKP菌株的抗菌活性。
全基因组测序确定这些分离株为ST101和ST307，携带包括blaNDM-1和blaOXA-48在内的耐药决定簇，分布在IncFII和IncFIB质粒复制子上。两株分离株均对β-内酰胺类、氨基糖苷类和氟喹诺酮类药物表现出广泛耐药，但对MEV仍敏感。表型分析显示，在没有高毒力相关基因的情况下，与参考菌株肺炎克雷伯菌ATCC 13883相比，生物膜形成和代谢活性增强。MEV对浮游菌和生物膜相关细胞均表现出杀菌活性，CRKP ST101的最低杀菌浓度（MBC）和最低生物膜清除浓度（MBEC）值为0.5/8μg/ml，CRKP ST307为0.12/8μg/ml，肺炎克雷伯菌ATCC 13883菌株为0.25/8μg/ml。在幼虫感染模型中，CRKP攻击后MEV显著提高了幼虫存活率。
这些发现表明MEV对浮游菌和生物膜相关的CRKP细胞具有活性，并强调需要进一步研究以管理由多重耐药菌引起的导管相关血流感染。
