Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections
Issued Date
2023-07-21
Resource Type
eISSN
25890042
Scopus ID
2-s2.0-85164719438
Journal Title
iScience
Volume
26
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
iScience Vol.26 No.7 (2023)
Suggested Citation
Wannigama D.L., Sithu Shein A.M., Hurst C., Monk P.N., Hongsing P., Phattharapornjaroen P., Fox Ditcham W.G., Ounjai P., Saethang T., Chantaravisoot N., Wapeesittipan P., Luk-in S., Sae-Joo S., Nilgate S., Rirerm U., Tanasatitchai C., Kueakulpattana N., Laowansiri M., Liao T., Kupwiwat R., Rojanathanes R., Ngamwongsatit N., Tungsanga S., Leelahavanichkul A., Devanga Ragupathi N.K., Badavath V.N., Hosseini Rad S.M.A., Kanjanabuch T., Hirankarn N., Storer R.J., Cui L., Amarasiri M., Ishikawa H., Higgins P.G., Stick S.M., Kicic A., Chatsuwan T., Abe S. Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections. iScience Vol.26 No.7 (2023). doi:10.1016/j.isci.2023.107215 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/88060
Title
Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections
Author(s)
Wannigama D.L.
Sithu Shein A.M.
Hurst C.
Monk P.N.
Hongsing P.
Phattharapornjaroen P.
Fox Ditcham W.G.
Ounjai P.
Saethang T.
Chantaravisoot N.
Wapeesittipan P.
Luk-in S.
Sae-Joo S.
Nilgate S.
Rirerm U.
Tanasatitchai C.
Kueakulpattana N.
Laowansiri M.
Liao T.
Kupwiwat R.
Rojanathanes R.
Ngamwongsatit N.
Tungsanga S.
Leelahavanichkul A.
Devanga Ragupathi N.K.
Badavath V.N.
Hosseini Rad S.M.A.
Kanjanabuch T.
Hirankarn N.
Storer R.J.
Cui L.
Amarasiri M.
Ishikawa H.
Higgins P.G.
Stick S.M.
Kicic A.
Chatsuwan T.
Abe S.
Sithu Shein A.M.
Hurst C.
Monk P.N.
Hongsing P.
Phattharapornjaroen P.
Fox Ditcham W.G.
Ounjai P.
Saethang T.
Chantaravisoot N.
Wapeesittipan P.
Luk-in S.
Sae-Joo S.
Nilgate S.
Rirerm U.
Tanasatitchai C.
Kueakulpattana N.
Laowansiri M.
Liao T.
Kupwiwat R.
Rojanathanes R.
Ngamwongsatit N.
Tungsanga S.
Leelahavanichkul A.
Devanga Ragupathi N.K.
Badavath V.N.
Hosseini Rad S.M.A.
Kanjanabuch T.
Hirankarn N.
Storer R.J.
Cui L.
Amarasiri M.
Ishikawa H.
Higgins P.G.
Stick S.M.
Kicic A.
Chatsuwan T.
Abe S.
Author's Affiliation
Yamagata Prefectural Central Hospital
Medizinische Fakultät
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Yamagata Prefectural University of Health Sciences
Perth Children's Hospital
Jichi Medical University
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Universitetet i Bergen
Chulalongkorn University
Sahlgrenska Akademin
King Chulalongkorn Memorial Hospital
Kasetsart University
Mae Fah Luang University
University of Otago
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Mahidol University
The Sheffield Medical School
Kitasato University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
Telethon Kids Institute
Partner Site Bonn-Cologne
Medizinische Fakultät
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Yamagata Prefectural University of Health Sciences
Perth Children's Hospital
Jichi Medical University
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Universitetet i Bergen
Chulalongkorn University
Sahlgrenska Akademin
King Chulalongkorn Memorial Hospital
Kasetsart University
Mae Fah Luang University
University of Otago
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Mahidol University
The Sheffield Medical School
Kitasato University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
Telethon Kids Institute
Partner Site Bonn-Cologne
Other Contributor(s)
Abstract
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.