Repurposing Zidovudine in combination with Tigecycline for treating carbapenem-resistant Enterobacteriaceae infections.

作者: S. M. S. Ng , J. S. P. Sioson , J. M. Yap , F. M. Ng , H. S. V. Ching

DOI: 10.1007/S10096-017-3114-5

关键词:

摘要: The global emergence of carbapenem-resistant Enterobacteriaceae (CRE) presents a significant clinical concern, prompting the WHO to prioritize CRE as top priority pathogen in their 2017 antibiotic-resistant bacteria list. Due fast-depleting antibiotic arsenal, clinicians are now resorting using once-abandoned, highly toxic antibiotics such polymyxins and aminoglycosides, creating an urgent need for new antibiotics. Drug repurposing, application approved drug therapeutic indication, is deemed plausible solution this problem. A total 1,163 FDA-approved drugs were screened activity against carbapenem- multidrug-resistant E. coli isolate single-point 10 μM assay. Hit compounds then assessed suitability repurposing. lead candidate was tested panel CREs, bactericidal/static determination assay, time-kill assay checkerboard evaluate its use combination with Tigecycline infections. Three identified. determined be Zidovudine (azidothymidine/AZT), oral anti-viral used HIV treatment. shown most promising treat systemic Further experiments should involve animal infection models.

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