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Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiellapneumoniae infections.
Wannigama, Dhammika Leshan; Sithu Shein, Aye Mya; Hurst, Cameron; Monk, Peter N; Hongsing, Parichart; Phattharapornjaroen, Phatthranit; Fox Ditcham, William Graham; Ounjai, Puey; Saethang, Thammakorn; Chantaravisoot, Naphat; Wapeesittipan, Pattama; Luk-In, Sirirat; Sae-Joo, Sasipen; Nilgate, Sumanee; Rirerm, Ubolrat; Tanasatitchai, Chanikan; Kueakulpattana, Naris; Laowansiri, Matchima; Liao, Tingting; Kupwiwat, Rosalyn; Rojanathanes, Rojrit; Ngamwongsatit, Natharin; Tungsanga, Somkanya; Leelahavanichkul, Asada; Devanga Ragupathi, Naveen Kumar; Badavath, Vishnu Nayak; Hosseini Rad, S M Ali; Kanjanabuch, Talerngsak; Hirankarn, Nattiya; Storer, Robin James; Cui, Longzhu; Amarasiri, Mohan; Ishikawa, Hitoshi; Higgins, Paul G; Stick, Stephen M; Kicic, Anthony; Chatsuwan, Tanittha; Abe, Shuichi.
Affiliation
  • Wannigama DL; Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan.
  • Sithu Shein AM; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Hurst C; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Monk PN; School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia.
  • Hongsing P; Biofilms and Antimicrobial Resistance Consortium of ODA Receiving Countries, The University of Sheffield, Sheffield, UK.
  • Phattharapornjaroen P; Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan.
  • Fox Ditcham WG; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Ounjai P; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Saethang T; Molly Wardaguga Research Centre, Charles Darwin University, Brisbane, QLD, Australia.
  • Chantaravisoot N; Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, UK.
  • Wapeesittipan P; Mae Fah Luang University Hospital, Chiang Rai, Thailand.
  • Luk-In S; School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand.
  • Sae-Joo S; Department of Emergency Medicine, Center of Excellence, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
  • Nilgate S; Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Academy, Gothenburg University, 40530 Gothenburg, Sweden.
  • Rirerm U; School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia.
  • Tanasatitchai C; Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • Kueakulpattana N; Department of Computer Science, Faculty of Science, Kasetsart University, Bangkok, Thailand.
  • Laowansiri M; Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Liao T; Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Kupwiwat R; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Rojanathanes R; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
  • Ngamwongsatit N; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Tungsanga S; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Leelahavanichkul A; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Devanga Ragupathi NK; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Badavath VN; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Hosseini Rad SMA; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Kanjanabuch T; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Hirankarn N; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Storer RJ; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Cui L; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Amarasiri M; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • Ishikawa H; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Higgins PG; Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Stick SM; Center of Excellence for Microcirculation, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Kicic A; Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan.
  • Chatsuwan T; Department of Dermatology. Faculty of Medicine Siriraj Hospital. Mahidol University, Bangkok, Thailand.
  • Abe S; Center of Excellence in Materials and Bio-Interfaces, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
iScience ; 26(7): 107215, 2023 Jul 21.
Article in En | MEDLINE | ID: mdl-37496674
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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: IScience Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: IScience Year: 2023 Document type: Article Affiliation country: Country of publication: