Biomedicine & Pharmacotherapy (Dec 2023)
Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection
- Aye Mya Sithu Shein,
- Dhammika Leshan Wannigama,
- Cameron Hurst,
- Peter N. Monk,
- Mohan Amarasiri,
- Vishnu Nayak Badavath,
- Phatthranit Phattharapornjaroen,
- William Graham Fox Ditcham,
- Puey Ounjai,
- Thammakorn Saethang,
- Naphat Chantaravisoot,
- Wanwara Thuptimdang,
- Sirirat Luk-in,
- Sumanee Nilgate,
- Ubolrat Rirerm,
- Chanikan Tanasatitchai,
- Naris Kueakulpattana,
- Matchima Laowansiri,
- Tingting Liao,
- Rosalyn Kupwiwat,
- Rojrit Rojanathanes,
- Natharin Ngamwongsatit,
- Arsa Thammahong,
- Hitoshi Ishikawa,
- Daniel Pletzer,
- Asada Leelahavanichkul,
- Naveen Kumar Devanga Ragupathi,
- Pattama Wapeesittipan,
- S.M. Ali Hosseini Rad,
- Talerngsak Kanjanabuch,
- Robin James Storer,
- Kazuhiko Miyanaga,
- Longzhu Cui,
- Hiroshi Hamamoto,
- Paul G. Higgins,
- Anthony Kicic,
- Tanittha Chatsuwan,
- Parichart Hongsing,
- Shuichi Abe
Affiliations
- 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
- Dhammika Leshan Wannigama
- 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; Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia; Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, United Kingdom; Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Yamagata Prefectural University of Health Sciences, Kamiyanagi, Yamagata 990-2212, Japan; Corresponding authors at: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
- Cameron Hurst
- Molly Wardaguga Research Centre, Charles Darwin University, Queensland, Australia
- Peter N. Monk
- Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, United Kingdom
- Mohan Amarasiri
- Laboratory of Environmental Hygiene, Department of Health Science, School of Allied Health Sciences, Kitasato University, Kitasato, Sagamihara-Minami, Kanagawa 252-0373, Japan
- Vishnu Nayak Badavath
- School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Hyderabad 509301, India
- 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, Western Australia, 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
- Wanwara Thuptimdang
- Institute of Biomedical Engineering, Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
- Sirirat Luk-in
- Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol 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
- Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
- 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, 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
- Arsa Thammahong
- Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
- Hitoshi Ishikawa
- Yamagata Prefectural University of Health Sciences, Kamiyanagi, Yamagata 990-2212, Japan
- Daniel Pletzer
- Department of Microbiology and Immunology, University of Otago, 720 Cumberland St., 9054 Dunedin, New Zealand
- Asada Leelahavanichkul
- Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, 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, United Kingdom; Department of Clinical Microbiology, Christian Medical College, Vellore, India
- Pattama Wapeesittipan
- Department of Clinical Science, University of Bergen, Bergen, Norway
- S.M. Ali Hosseini Rad
- Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, 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
- Robin James Storer
- Office of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Kazuhiko Miyanaga
- Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
- Longzhu Cui
- Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
- Hiroshi Hamamoto
- Department of Infectious Diseases, Faculty of Medicine Yamagata University, Yamagata, 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
- Anthony Kicic
- Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, Medical School, The University of Western Australia, Nedlands 6009, Western Australia, Australia; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands 6009, Western Australia, Australia; School of Public Health, Curtin University, Bentley 6102, Western Australia, Australia; Corresponding author at: Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia.
- 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 authors at: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
- Parichart Hongsing
- School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand; Mae Fah Luang University Hospital, Chiang Rai, Thailand; Corresponding author at: School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand.
- Shuichi Abe
- Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, United Kingdom; Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan; Corresponding author at: Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, United Kingdom
- Journal volume & issue
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Vol. 168
p. 115793
Abstract
Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant combination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.
