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 KupwiwatRojrit 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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number115793
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume168
DOIs
Publication statusPublished - Dec 2023

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