Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection - 11/11/23
Doi : 10.1016/j.biopha.2023.115793
Aye Mya Sithu Shein a, b, 1, Dhammika Leshan Wannigama a, b, c, d, e, f, g, ⁎, 2 
, Cameron Hurst h, 1, Peter N. Monk i, Mohan Amarasiri j, Vishnu Nayak Badavath k, Phatthranit Phattharapornjaroen l, m, William Graham Fox Ditcham d, Puey Ounjai n, Thammakorn Saethang o, Naphat Chantaravisoot p, q, Wanwara Thuptimdang r, Sirirat Luk-in s, Sumanee Nilgate a, b, Ubolrat Rirerm a, b, Chanikan Tanasatitchai f, Naris Kueakulpattana a, b, Matchima Laowansiri a, b, Tingting Liao t, u, Rosalyn Kupwiwat f, v, Rojrit Rojanathanes w, Natharin Ngamwongsatit x, Arsa Thammahong b, c, Hitoshi Ishikawa g, Daniel Pletzer y, Asada Leelahavanichkul b, z, Naveen Kumar Devanga Ragupathi f, aa, ab, Pattama Wapeesittipan ac, S.M. Ali Hosseini Rad ad, ae, Talerngsak Kanjanabuch af, ag, ah, ai, Robin James Storer aj, Kazuhiko Miyanaga ak, Longzhu Cui ak, Hiroshi Hamamoto al, Paul G. Higgins am, an, ao, 1, Anthony Kicic ap, aq, ar, as, ⁎ , Tanittha Chatsuwan a, b, ⁎ , Parichart Hongsing at, au, ⁎ , Shuichi Abe e, f, ⁎
, Cameron Hurst h, 1, Peter N. Monk i, Mohan Amarasiri j, Vishnu Nayak Badavath k, Phatthranit Phattharapornjaroen l, m, William Graham Fox Ditcham d, Puey Ounjai n, Thammakorn Saethang o, Naphat Chantaravisoot p, q, Wanwara Thuptimdang r, Sirirat Luk-in s, Sumanee Nilgate a, b, Ubolrat Rirerm a, b, Chanikan Tanasatitchai f, Naris Kueakulpattana a, b, Matchima Laowansiri a, b, Tingting Liao t, u, Rosalyn Kupwiwat f, v, Rojrit Rojanathanes w, Natharin Ngamwongsatit x, Arsa Thammahong b, c, Hitoshi Ishikawa g, Daniel Pletzer y, Asada Leelahavanichkul b, z, Naveen Kumar Devanga Ragupathi f, aa, ab, Pattama Wapeesittipan ac, S.M. Ali Hosseini Rad ad, ae, Talerngsak Kanjanabuch af, ag, ah, ai, Robin James Storer aj, Kazuhiko Miyanaga ak, Longzhu Cui ak, Hiroshi Hamamoto al, Paul G. Higgins am, an, ao, 1, Anthony Kicic ap, aq, ar, as, ⁎ , Tanittha Chatsuwan a, b, ⁎ , Parichart Hongsing at, au, ⁎ , Shuichi Abe e, f, ⁎ a Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
b Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
c Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
d School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
e Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, United Kingdom
f Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
g Yamagata Prefectural University of Health Sciences, Kamiyanagi, Yamagata 990-2212, Japan
h Molly Wardaguga Research Centre, Charles Darwin University, Queensland, Australia
i Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, United Kingdom
j Laboratory of Environmental Hygiene, Department of Health Science, School of Allied Health Sciences, Kitasato University, Kitasato, Sagamihara-Minami, Kanagawa 252-0373, Japan
k School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Hyderabad 509301, India
l Department of Emergency Medicine, Center of Excellence, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
m Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Academy, Gothenburg University, 40530 Gothenburg, Sweden
n Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand
o Department of Computer Science, Faculty of Science, Kasetsart University, Bangkok, Thailand
p Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
q Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
r Institute of Biomedical Engineering, Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
s Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
t Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
u Center of Excellence for Microcirculation, Faculty of Medicine, Chulalongkorn University, Thailand
v Department of Dermatology. Faculty of Medicine Siriraj Hospital. Mahidol University, Bangkok, Thailand
w Center of Excellence in Materials and Bio-Interfaces, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
x Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand
y Department of Microbiology and Immunology, University of Otago, 720 Cumberland St., 9054 Dunedin, New Zealand
z Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
aa Department of Chemical and Biological Engineering, The University of Sheffield, Sheffield, United Kingdom
ab Department of Clinical Microbiology, Christian Medical College, Vellore, India
ac Department of Clinical Science, University of Bergen, Bergen, Norway
ad Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand
ae Center of Excellence in Immunology and Immune-Mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand
af Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
ag Center of Excellence in Kidney Metabolic Disorders, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
ah Dialysis Policy and Practice Program (DiP3), School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
ai Peritoneal Dialysis Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
aj Office of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
ak Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
al Department of Infectious Diseases, Faculty of Medicine Yamagata University, Yamagata, Japan
am Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
an German Centre for Infection Research, Partner site Bonn-Cologne, Cologne, Germany
ao Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50935 Cologne, Germany
ap Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia
aq Centre for Cell Therapy and Regenerative Medicine, Medical School, The University of Western Australia, Nedlands 6009, Western Australia, Australia
ar Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands 6009, Western Australia, Australia
as School of Public Health, Curtin University, Bentley 6102, Western Australia, Australia
at School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand
au Mae Fah Luang University Hospital, Chiang Rai, Thailand
⁎Corresponding authors at: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkokThailand⁎⁎Corresponding author at: Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia.Telethon Kids Institute, University of Western AustraliaNedlandsWestern Australia6009Australia⁎⁎⁎Corresponding author at: School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand.School of Integrative Medicine, Mae Fah Luang UniversityChiang RaiThailand⁎⁎⁎⁎Corresponding author at: Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, United KingdomBiofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of SheffieldSheffieldUnited Kingdom
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | New treatments needed for multidrug-resistant Pseudomonas aeruginosa infections. |
• | Phage therapy is limited due to the resistance and biofilm penetration. |
• | CaEDTA demonstrated the ability to enhance the effectiveness of antibiotics. |
• | Inhaling phage + CaEDTA restores P. aeruginosa sensitivity to Ceftazidime/Avibactam. |
• | This shows potential as a therapy for chronic respiratory tract infections. |
Keywords : Intranasal, Phage, CaEDTA, Combination therapy, Pseudomonas aeruginosa, Lung, Infection, Antibiotic resistance
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© 2023
The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
Vol 168
Article 115793- décembre 2023 Retour au numéro
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