Synergistic Combination of AS101 and Azidothymidine against Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae

Pathogens

Po-Liang Lu¹  Lin Lin²  Liang-Chun Wang³  Sung-Pin Tseng⁴  Chung-Lin Sung⁴  Tsung-Ying Yang⁴  Wei-Chun Hung⁵ 

[1] Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Department of Culinary Art, I-Shou University, Kaohsiung 84001, Taiwan;Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan;Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;

关键词: carbapenem-resistant Enterobacteriaceae (CRE);    synergistic activity;    AS101;    azidothymidine;   

DOI  :  10.3390/pathogens10121552

来源: DOAJ

【 摘 要 】

Owing to the over usage of carbapenems, carbapenem resistance has become a vital threat worldwide, and, thus, the World Health Organization announced the carbapenem-resistant Enterobacteriaceae (CRE) as the critical priority for antibiotic development in 2017. In the current situation, combination therapy would be one solution against CRE. Azidothymidine (AZT), a thymidine analog, has demonstrated its synergistically antibacterial activities with other antibiotics. The unexpected antimicrobial activity of the immunomodulator ammonium trichloro(dioxoethylene-o,o’)tellurate (AS101) has been reported against carbapenem-resistant Klebsiella pneumoniae (CRKP). Here, we sought to investigate the synergistic activity between AS101 and AZT against 12 CRKP clinical isolates. According to the gene detection results, the bla_OXA-1 (7/12, 58.3%)_, bla_DHA (7/12, 58.3%), and bla_KPC (7/12, 58.3%) genes were the most prevalent ESBL, AmpC, and carbapenemase genes, respectively. The checkerboard analysis demonstrated the remarkable synergism between AS101 and AZT, with the observable decrease in the MIC value for two agents and the fractional inhibitory concentration (FIC) index ≤0.5 in all strains. Hence, the combination of AS101 and azidothymidine could be a potential treatment option against CRKP for drug development.

【 授权许可】

Unknown