학술논문
Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections
Document Type
article
Author
Dhammika Leshan Wannigama; Aye Mya Sithu Shein; Cameron Hurst; Peter N. Monk; Parichart Hongsing; Phatthranit Phattharapornjaroen; William Graham Fox Ditcham; Puey Ounjai; Thammakorn Saethang; Naphat Chantaravisoot; Pattama Wapeesittipan; Sirirat Luk-in; Sasipen Sae-Joo; Sumanee Nilgate; Ubolrat Rirerm; Chanikan Tanasatitchai; Naris Kueakulpattana; Matchima Laowansiri; Tingting Liao; Rosalyn Kupwiwat; Rojrit Rojanathanes; Natharin Ngamwongsatit; Somkanya Tungsanga; Asada Leelahavanichkul; Naveen Kumar Devanga Ragupathi; Vishnu Nayak Badavath; S.M. Ali Hosseini Rad; Talerngsak Kanjanabuch; Nattiya Hirankarn; Robin James Storer; Longzhu Cui; Mohan Amarasiri; Hitoshi Ishikawa; Paul G. Higgins; Stephen M. Stick; Anthony Kicic; Tanittha Chatsuwan; Shuichi Abe
Source
iScience, Vol 26, Iss 7, Pp 107215- (2023)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mortality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations provide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.