iScience (Jul 2023)
Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections
- 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
Affiliations
- Dhammika Leshan Wannigama
- Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia; Biofilms and Antimicrobial Resistance Consortium of ODA Receiving Countries, The University of Sheffield, Sheffield, UK; Pathogen Hunter’s Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Corresponding author
- Aye Mya Sithu Shein
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Cameron Hurst
- Molly Wardaguga Research Centre, Charles Darwin University, Brisbane, QLD, Australia
- Peter N. Monk
- Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, UK
- Parichart Hongsing
- Mae Fah Luang University Hospital, Chiang Rai, Thailand; School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand; Corresponding author
- Phatthranit Phattharapornjaroen
- Department of Emergency Medicine, Center of Excellence, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Academy, Gothenburg University, 40530 Gothenburg, Sweden
- William Graham Fox Ditcham
- School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
- Puey Ounjai
- Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand
- Thammakorn Saethang
- Department of Computer Science, Faculty of Science, Kasetsart University, Bangkok, Thailand
- Naphat Chantaravisoot
- Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Pattama Wapeesittipan
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Sirirat Luk-in
- Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
- Sasipen Sae-Joo
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Sumanee Nilgate
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Ubolrat Rirerm
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Chanikan Tanasatitchai
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Naris Kueakulpattana
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Matchima Laowansiri
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Tingting Liao
- Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Microcirculation, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Rosalyn Kupwiwat
- Pathogen Hunter’s Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Department of Dermatology. Faculty of Medicine Siriraj Hospital. Mahidol University, Bangkok, Thailand
- Rojrit Rojanathanes
- Center of Excellence in Materials and Bio-Interfaces, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
- Natharin Ngamwongsatit
- Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand
- Somkanya Tungsanga
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of General Internal Medicine-Nephrology Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Asada Leelahavanichkul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
- Naveen Kumar Devanga Ragupathi
- Pathogen Hunter’s Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Department of Chemical and Biological Engineering, The University of Sheffield, Sheffield, UK; Department of Clinical Microbiology, Christian Medical College, Vellore, India
- Vishnu Nayak Badavath
- School of Pharmacy & Technology Management, SVKM’s Narsee Monjee Institute of Management Studies (NMIMS), Hyderabad 509301, India
- S.M. Ali Hosseini Rad
- Department of Microbiology and Immunology, University of Otago, Dunedin, Otago 9010, New Zealand; Center of Excellence in Immunology and Immune-Mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand
- Talerngsak Kanjanabuch
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Kidney Metabolic Disorders, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Dialysis Policy and Practice Program (DiP3), School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Peritoneal Dialysis Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Nattiya Hirankarn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Immunology and Immune-Mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand
- Robin James Storer
- Office of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Longzhu Cui
- Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
- Mohan Amarasiri
- Laboratory of Environmental Hygiene, Department of Health Science, School of Allied Health Sciences, Kitasato University, Kitasato, Sagamihara-Minami, Kanagawa 252-0373, Japan
- Hitoshi Ishikawa
- Yamagata Prefectural University of Health Sciences, Kamiyanagi, Yamagata 990-2212, Japan
- Paul G. Higgins
- Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; German Centre for Infection Research, Partner site Bonn-Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50935 Cologne, Germany
- Stephen M. Stick
- Telethon Kids Institute, University of Western Australia, Nedlands, WA 6009, Australia; Centre for Cell Therapy and Regenerative Medicine, Medical School, The University of Western Australia, Nedlands, WA 6009, Australia; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA 6009, Australia
- Anthony Kicic
- Telethon Kids Institute, University of Western Australia, Nedlands, WA 6009, Australia; Centre for Cell Therapy and Regenerative Medicine, Medical School, The University of Western Australia, Nedlands, WA 6009, Australia; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA 6009, Australia; School of Public Health, Curtin University, Bentley, WA 6102, Australia; Corresponding author
- Tanittha Chatsuwan
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Corresponding author
- Shuichi Abe
- Biofilms and Antimicrobial Resistance Consortium of ODA Receiving Countries, The University of Sheffield, Sheffield, UK; Pathogen Hunter’s Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 7
p. 107215
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.
