TY - JOUR
T1 - Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections
AU - Shein, Aye Mya Sithu
AU - Wannigama, Dhammika Leshan
AU - Higgins, Paul G.
AU - Hurst, Cameron
AU - Abe, Shuichi
AU - Hongsing, Parichart
AU - Chantaravisoot, Naphat
AU - Saethang, Thammakorn
AU - Luk-in, Sirirat
AU - Liao, Tingting
AU - Nilgate, Sumanee
AU - Rirerm, Ubolrat
AU - Kueakulpattana, Naris
AU - Laowansiri, Matchima
AU - Srisakul, Sukrit
AU - Muhummudaree, Netchanok
AU - Techawiwattanaboon, Teerasit
AU - Gan, Lin
AU - Xu, Chenchen
AU - Kupwiwat, Rosalyn
AU - Phattharapornjaroen, Phatthranit
AU - Rojanathanes, Rojrit
AU - Leelahavanichkul, Asada
AU - Chatsuwan, Tanittha
N1 - Funding Information:
This work was supported by a grant from the 90th Year Anniversary Ratchadapiseksompotch Endowment Fund from the Faculty of Medicine and Graduate School, Chulalongkorn University, Bangkok, Thailand and Ratcha-dapiseksompotch Fund, Chulalongkorn University Bangkok, Thailand (grant No. CU_GR_63_119_30_26). Aye Mya Sithu Shein was supported under the Chulalongkorn University Graduate Scholarship Program for ASEAN Countries. Dhammika Leshan Wannigama was supported by Chulalongkorn University (Second Century Fund-C2F Fellowship), and the University of Western Australia (Overseas Research Experience Fellowship). The sponsor(s) had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118684781&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-01052-5
DO - 10.1038/s41598-021-01052-5
M3 - Article
C2 - 34737361
AN - SCOPUS:85118684781
VL - 11
SP - 1
EP - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 21676
ER -