Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85209720118
Journal Title
Scientific Reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Shein A.M.S., Wannigama D.L., Hurst C., Monk P.N., Amarasiri M., Wongsurawat T., Jenjaroenpun P., Phattharapornjaroen P., Ditcham W.G.F., Ounjai P., Saethang T., Chantaravisoot N., Badavath V.N., Luk-in S., Nilgate S., Rirerm U., Srisakul S., Kueakulpattana N., Laowansiri M., Rad S.M.A.H., Wacharapluesadee S., Rodpan A., Ngamwongsatit N., Thammahong A., Ishikawa H., Storer R.J., Leelahavanichkul A., Ragupathi N.K.D., Classen A.Y., Kanjanabuch T., Pletzer D., Miyanaga K., Cui L., Hamamoto H., Higgins P.G., Kicic A., Chatsuwan T., Hongsing P., Abe S. Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-024-79924-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102212
Title
Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae
Author(s)
Shein A.M.S.
Wannigama D.L.
Hurst C.
Monk P.N.
Amarasiri M.
Wongsurawat T.
Jenjaroenpun P.
Phattharapornjaroen P.
Ditcham W.G.F.
Ounjai P.
Saethang T.
Chantaravisoot N.
Badavath V.N.
Luk-in S.
Nilgate S.
Rirerm U.
Srisakul S.
Kueakulpattana N.
Laowansiri M.
Rad S.M.A.H.
Wacharapluesadee S.
Rodpan A.
Ngamwongsatit N.
Thammahong A.
Ishikawa H.
Storer R.J.
Leelahavanichkul A.
Ragupathi N.K.D.
Classen A.Y.
Kanjanabuch T.
Pletzer D.
Miyanaga K.
Cui L.
Hamamoto H.
Higgins P.G.
Kicic A.
Chatsuwan T.
Hongsing P.
Abe S.
Wannigama D.L.
Hurst C.
Monk P.N.
Amarasiri M.
Wongsurawat T.
Jenjaroenpun P.
Phattharapornjaroen P.
Ditcham W.G.F.
Ounjai P.
Saethang T.
Chantaravisoot N.
Badavath V.N.
Luk-in S.
Nilgate S.
Rirerm U.
Srisakul S.
Kueakulpattana N.
Laowansiri M.
Rad S.M.A.H.
Wacharapluesadee S.
Rodpan A.
Ngamwongsatit N.
Thammahong A.
Ishikawa H.
Storer R.J.
Leelahavanichkul A.
Ragupathi N.K.D.
Classen A.Y.
Kanjanabuch T.
Pletzer D.
Miyanaga K.
Cui L.
Hamamoto H.
Higgins P.G.
Kicic A.
Chatsuwan T.
Hongsing P.
Abe S.
Author's Affiliation
Yamagata Prefectural Central Hospital
Medizinische Fakultät
Faculty of Science, Mahidol University
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Yamagata Prefectural University of Health Sciences
Perth Children's Hospital
Jichi Medical University
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Chulalongkorn University
Yamagata University Faculty of Medicine
Chulabhorn Royal Academy
King Chulalongkorn Memorial Hospital
Kasetsart University
Mae Fah Luang University
University of Otago
Faculty of Medicine, Thammasat University
Mahidol University
Thammasat University
The Sheffield Medical School
Tohoku University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
The Kids Research Institute Australia
Partner Site Bonn-Cologne
Medizinische Fakultät
Faculty of Science, Mahidol University
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Yamagata Prefectural University of Health Sciences
Perth Children's Hospital
Jichi Medical University
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Chulalongkorn University
Yamagata University Faculty of Medicine
Chulabhorn Royal Academy
King Chulalongkorn Memorial Hospital
Kasetsart University
Mae Fah Luang University
University of Otago
Faculty of Medicine, Thammasat University
Mahidol University
Thammasat University
The Sheffield Medical School
Tohoku University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
The Kids Research Institute Australia
Partner Site Bonn-Cologne
Corresponding Author(s)
Other Contributor(s)
Abstract
The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 and K2/wzi-2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae. Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages’ selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo.