Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections

Aye Mya Sithu Shein, Dhammika Leshan Wannigama, Paul G. Higgins, Cameron Hurst, Shuichi Abe, Parichart Hongsing, Naphat Chantaravisoot, Thammakorn Saethang, Sirirat Luk-in, Tingting Liao, Sumanee Nilgate, Ubolrat Rirerm, Naris Kueakulpattana, Matchima Laowansiri, Sukrit Srisakul, Netchanok Muhummudaree, Teerasit Techawiwattanaboon, Lin Gan, Chenchen Xu, Rosalyn KupwiwatPhatthranit Phattharapornjaroen, Rojrit Rojanathanes, Asada Leelahavanichkul, Tanittha Chatsuwan

Research output: Contribution to journalArticlepeer-review

Abstract

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25–1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

Original languageEnglish
Article number21676
Pages (from-to)1-13
Number of pages13
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

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