Journal
MICROORGANISMS
Volume 8, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms8121964
Keywords
Klebsiella pneumoniae; azidothymidine; caenorhabditis elegans
Categories
Funding
- Ministry of Science and Technology of Taiwan [MOST 109-2320-B-037-027]
- Kaohsiung Medical University Research Foundation [M109001]
- Kaohsiung Medical University Research Center Grant [KMU-TC109B02]
- National Sun Yat-sen University-Kaohsiung Medical University (NSYSU-KMU) Joint Research Project [NSYSUKMU 109-I005]
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Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the last-resort antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of <= 0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT-colistin combination could be a potentially favorable therapeutic option for treating CCRKP.
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