Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae
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.
Authors
- Apaporn Rodpan
- Supaporn Wacharapluesadee (ORCID: https://orcid.org/0000-0001-7636-1900)
- Piroon Jenjaroenpun (ORCID: https://orcid.org/0000-0002-1555-401X)
- Naphat Chantaravisoot (ORCID: https://orcid.org/0000-0003-3946-1798)
- Phatthranit Phattharapornjaroen (ORCID: https://orcid.org/0000-0002-4391-2929)
- Asada Leelahavanichkul (ORCID: https://orcid.org/0000-0002-5566-6403)
- Sumanee Nilgate
- Puey Ounjai (ORCID: https://orcid.org/0000-0002-3335-6199)
- William Ditcham
- Thidathip Wongsurawat (ORCID: https://orcid.org/0000-0002-3659-2074)
- Mohan Amarasiri (ORCID: https://orcid.org/0000-0002-3509-3433)
- Matchima Laowansiri
- Longzhu Cui (ORCID: https://orcid.org/0000-0002-8909-3885)
- Natharin Ngamwongsatit (ORCID: https://orcid.org/0000-0001-9569-396X)
- Talerngsak Kanjanabuch (ORCID: https://orcid.org/0000-0002-2996-8934)
- Anthony Kicic (ORCID: https://orcid.org/0000-0002-0008-9733)
- Naris Kueakulpattana (ORCID: https://orcid.org/0000-0003-0451-6509)
- Parichart Hongsing (ORCID: https://orcid.org/0000-0002-2031-3472)
- Dhammika Leshan Wannigama (ORCID: https://orcid.org/0000-0001-6316-1221)
- Cameron Hurst (ORCID: https://orcid.org/0000-0002-4577-8962)
- Thammakorn Saethang (ORCID: https://orcid.org/0000-0002-0397-7111)
- Tanittha Chatsuwan (ORCID: https://orcid.org/0000-0003-1717-1167)
- Daniel Pletzer (ORCID: https://orcid.org/0000-0001-5750-7505)
- Peter N. Monk (ORCID: https://orcid.org/0000-0003-4637-3059)
- Hitoshi Ishikawa (ORCID: https://orcid.org/0000-0002-0046-9787)
- Annika Y. Claßen (ORCID: https://orcid.org/0000-0003-2905-5139)
- Hiroshi Hamamoto (ORCID: https://orcid.org/0000-0001-9315-7442)
- Vishnu Nayak Badavath (ORCID: https://orcid.org/0000-0002-6433-2691)
- Shuichi Abe
- Robin James Storer (ORCID: https://orcid.org/0000-0003-0157-2919)
- Arsa Thammahong (ORCID: https://orcid.org/0000-0002-0482-4176)
- Aye Mya Sithu Shein
- Kazuhiko Miyanaga (ORCID: https://orcid.org/0000-0002-3483-9491)
- Sukrit Srisakul
- Naveen Kumar Devanga Ragupathi (ORCID: https://orcid.org/0000-0001-8667-7132)
- Seyed Mohammad Ali Hosseini Rad (ORCID: https://orcid.org/0000-0002-7107-3528)
- Paul G. Higgins (ORCID: https://orcid.org/0000-0001-8677-9454)
- Ubolrat Rirerm
- Sirirat Luk-in (ORCID: https://orcid.org/0000-0003-0869-7562)
Institutions
- Thammasat University (TH)
- Yamagata University (JP)
- Thai Red Cross Society (TH)
- Siriraj Hospital (TH)
- Jichi Medical University (JP)
- Chulalongkorn University (TH)
- Christian Medical College, Vellore (IN)
- The Kids Research Institute Australia (AU)
- The University of Western Australia (AU)
- University of Cologne (DE)
- Kasetsart University (TH)
- Tohoku University (JP)
- Curtin University (AU)
- Narsee Monjee Institute of Management Studies (IN)
- Mahidol University (TH)
- Princess Margaret Hospital for Children (AU)
- King Chulalongkorn Memorial Hospital (TH)
- Charles Darwin University (AU)
- Mae Fah Luang University (TH)
- Chulabhorn Hospital (TH)
- German Center for Infection Research (DE)
- Yamagata Prefectural Central Hospital (JP)
- University Hospital Cologne (DE)
- Yamagata University Hospital (JP)
- University of Otago (NZ)
- University of Sheffield (GB)
- Yamagata Prefectural University of Health Sciences (JP)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-11-22
- DOI
- https://doi.org/10.1038/s41598-024-79924-9
- Citations
- 18
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 8.26
Funders
- Chulalongkorn University
- Mahidol University
- National Research Council of Thailand
- Thailand Science Research and Innovation