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Abstract
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 blaOXA-1 (7/12, 58.3%), blaDHA (7/12, 58.3%), and blaKPC (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.
Highlights
Carbapenem-resistant Enterobacteriaceae (CRE) was announced as the critical priority for antibiotic development in 2017 [1]
In a phase I clinical trial for the combination of AZT and colistin, the results revealed that a dosage of 2 million IU CMS plus 100 mg AZT twice a day might be sufficient for urinary tract infections (UTIs) [15]
Previous efforts posed that AS101 could be a potential option to treat carbapenem-resistant Klebsiella pneumoniae (CRKP), our study described that the minimum inhibitory concentration (MIC) values of AS101 against CRKP was up to 32 μg/mL [23], which is not far away from its 50% cytotoxicity level (145 μg/mL) [21]
Summary
Carbapenem-resistant Enterobacteriaceae (CRE) was announced as the critical priority for antibiotic development in 2017 [1]. The COVID-19 pandemic promoted the spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) [2], highlighting an urgent need for novel treatment options. The high carbapenem-resistant rates were revealed in some parts of Europe [3], especially Southern Europe. A regional resistance surveillance program in Asia-Pacific reported 25% carbapenem-resistant rate in K. pneumoniae for India and 5% for both the Philippines and Thailand [5]. A more recent surveillance conducted in Taiwan, 2018, described a 7.2% carbapenem-resistant rate in 346 K. pneumoniae isolates [6]. In view of the aforementioned reports, the development of novel therapeutic options to address CRKP is urgently needed
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