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

doi:10.1016/j.biopha.2023.115793

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

Molly Wardaguga Research Centre

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5 Citations (Scopus)

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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 language	English
Article number	115793
Pages (from-to)	1-6
Number of pages	6
Journal	Biomedicine and Pharmacotherapy
Volume	168
DOIs	https://doi.org/10.1016/j.biopha.2023.115793
Publication status	Published - Dec 2023

Bibliographical note

Funding Information:
This research is funded by Thailand Science Research and Innovation Fund Chulalongkorn University ( CU_FRB65_hea(43)_050_30_31 ). Aye Mya Sithu Shein was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship). Dhammika Leshan Wannigama was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship), the University of Western Australia (Overseas Research Experience Fellowship), and Yamagata Prefectural Central Hospital , Yamagata, Japan (Clinical Residency Fellowship). AK is a Rothwell Family Fellow . The sponsor(s) had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Publisher Copyright:
© 2023 The Authors

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Shein, A. M. S., Wannigama, D. L., Hurst, C., Monk, P. N., Amarasiri, M., Badavath, V. N., Phattharapornjaroen, P., Ditcham, W. G. F., Ounjai, P., Saethang, T., Chantaravisoot, N., Thuptimdang, W., Luk-in, S., Nilgate, S., Rirerm, U., Tanasatitchai, C., Kueakulpattana, N., Laowansiri, M., Liao, T., ... Abe, S. (2023). Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection. Biomedicine and Pharmacotherapy, 168, 1-6. Article 115793. https://doi.org/10.1016/j.biopha.2023.115793

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title = "Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection",

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.",

keywords = "Antibiotic resistance, CaEDTA, Combination therapy, Infection, Intranasal, Lung, Phage, Pseudomonas aeruginosa",

author = "Shein, {Aye Mya Sithu} and Wannigama, {Dhammika Leshan} and Cameron Hurst and Monk, {Peter N.} and Mohan Amarasiri and Badavath, {Vishnu Nayak} and Phatthranit Phattharapornjaroen and Ditcham, {William Graham Fox} and Puey Ounjai and Thammakorn Saethang and Naphat Chantaravisoot and Wanwara Thuptimdang and Sirirat Luk-in and Sumanee Nilgate and Ubolrat Rirerm and Chanikan Tanasatitchai and Naris Kueakulpattana and Matchima Laowansiri and Tingting Liao and Rosalyn Kupwiwat and Rojrit Rojanathanes and Natharin Ngamwongsatit and Arsa Thammahong and Hitoshi Ishikawa and Daniel Pletzer and Asada Leelahavanichkul and Ragupathi, {Naveen Kumar Devanga} and Pattama Wapeesittipan and {Ali Hosseini Rad}, {S. M.} and Talerngsak Kanjanabuch and Storer, {Robin James} and Kazuhiko Miyanaga and Longzhu Cui and Hiroshi Hamamoto and Higgins, {Paul G.} and Anthony Kicic and Tanittha Chatsuwan and Parichart Hongsing and Shuichi Abe",

note = "Funding Information: This research is funded by Thailand Science Research and Innovation Fund Chulalongkorn University ( CU_FRB65_hea(43)_050_30_31 ). Aye Mya Sithu Shein was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship). Dhammika Leshan Wannigama was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship), the University of Western Australia (Overseas Research Experience Fellowship), and Yamagata Prefectural Central Hospital , Yamagata, Japan (Clinical Residency Fellowship). AK is a Rothwell Family Fellow . The sponsor(s) had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = dec,

doi = "10.1016/j.biopha.2023.115793",

language = "English",

volume = "168",

pages = "1--6",

journal = "Biomedicine and Pharmacotherapy",

issn = "0753-3322",

publisher = "Elsevier Masson",

}

Shein, AMS, Wannigama, DL, Hurst, C, Monk, PN, Amarasiri, M, Badavath, VN, Phattharapornjaroen, P, Ditcham, WGF, Ounjai, P, Saethang, T, Chantaravisoot, N, Thuptimdang, W, Luk-in, S, Nilgate, S, Rirerm, U, Tanasatitchai, C, Kueakulpattana, N, Laowansiri, M, Liao, T, Kupwiwat, R, Rojanathanes, R, Ngamwongsatit, N, Thammahong, A, Ishikawa, H, Pletzer, D, Leelahavanichkul, A, Ragupathi, NKD, Wapeesittipan, P, Ali Hosseini Rad, SM, Kanjanabuch, T, Storer, RJ, Miyanaga, K, Cui, L, Hamamoto, H, Higgins, PG, Kicic, A, Chatsuwan, T, Hongsing, P & Abe, S 2023, 'Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection', Biomedicine and Pharmacotherapy, vol. 168, 115793, pp. 1-6. https://doi.org/10.1016/j.biopha.2023.115793

Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection. / Shein, Aye Mya Sithu; Wannigama, Dhammika Leshan; Hurst, Cameron et al.
In: Biomedicine and Pharmacotherapy, Vol. 168, 115793, 12.2023, p. 1-6.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection

AU - Shein, Aye Mya Sithu

AU - Wannigama, Dhammika Leshan

AU - Hurst, Cameron

AU - Monk, Peter N.

AU - Amarasiri, Mohan

AU - Badavath, Vishnu Nayak

AU - Phattharapornjaroen, Phatthranit

AU - Ditcham, William Graham Fox

AU - Ounjai, Puey

AU - Saethang, Thammakorn

AU - Chantaravisoot, Naphat

AU - Thuptimdang, Wanwara

AU - Luk-in, Sirirat

AU - Nilgate, Sumanee

AU - Rirerm, Ubolrat

AU - Tanasatitchai, Chanikan

AU - Kueakulpattana, Naris

AU - Laowansiri, Matchima

AU - Liao, Tingting

AU - Kupwiwat, Rosalyn

AU - Rojanathanes, Rojrit

AU - Ngamwongsatit, Natharin

AU - Thammahong, Arsa

AU - Ishikawa, Hitoshi

AU - Pletzer, Daniel

AU - Leelahavanichkul, Asada

AU - Ragupathi, Naveen Kumar Devanga

AU - Wapeesittipan, Pattama

AU - Ali Hosseini Rad, S. M.

AU - Kanjanabuch, Talerngsak

AU - Storer, Robin James

AU - Miyanaga, Kazuhiko

AU - Cui, Longzhu

AU - Hamamoto, Hiroshi

AU - Higgins, Paul G.

AU - Kicic, Anthony

AU - Chatsuwan, Tanittha

AU - Hongsing, Parichart

AU - Abe, Shuichi

N1 - Funding Information: This research is funded by Thailand Science Research and Innovation Fund Chulalongkorn University ( CU_FRB65_hea(43)_050_30_31 ). Aye Mya Sithu Shein was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship). Dhammika Leshan Wannigama was supported by Chulalongkorn University (Second Century Fund- C2F Fellowship), the University of Western Australia (Overseas Research Experience Fellowship), and Yamagata Prefectural Central Hospital , Yamagata, Japan (Clinical Residency Fellowship). AK is a Rothwell Family Fellow . The sponsor(s) had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: © 2023 The Authors

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - Antibiotic resistance

KW - CaEDTA

KW - Combination therapy

KW - Infection

KW - Intranasal

KW - Lung

KW - Phage

KW - Pseudomonas aeruginosa

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U2 - 10.1016/j.biopha.2023.115793

DO - 10.1016/j.biopha.2023.115793

M3 - Article

AN - SCOPUS:85175030390

SN - 0753-3322

VL - 168

SP - 1

EP - 6

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

M1 - 115793

ER -

Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection

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