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

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

Health of adults living with a clinically significant haemoglobinopathy in New South Wales, Australia.

AIM: To comprehensively review the health needs of patients living with clinically significant haemoglobinopathies (thalassaemia and sickle-cell disease (SCD)) in New South Wales, Australia. METHODS: A survey-based health needs assessment was undertaken in outpatients cared for at five tertiary institutions in metropolitan and regional centres. Sixty-three of 121 adults (approximately 80-90% of adult patients with transfusion-requiring haemoglobinopathies in New South Wales) completed an in-house and commercial health-related quality assessment survey (SF-36v2). RESULTS: Subjects came from more than eight world regions, with those with SCD being more likely to be born outside of Australia than subjects with thalassaemia (P < 0.001, likelihood ratio 20.64) as well as more likely to have been refugees (26% vs 2%). The population contained socially disadvantaged subjects with 13 subjects (20.6%) having incomes below the Australian poverty line. Complications of thalassaemia were comparable to previous international reports although our subjects had a high rate of secondary amenorrhea (>12 months = 27%) and surgical splenectomy (55.6%). Use of hydroxyurea in SCD was less than expected with only 46.6% of subjects having prior use. Lack of universal access to magnetic resonance imaging-guided chelation (international best practice) was evident, although 65.5% had been able to access magnetic resonance imaging through clinical trial, or self-funding. CONCLUSIONS: Patients with SCD and thalassaemia experience considerable morbidity and mortality and require complex, multidisciplinary care. This study revealed both variance from international best practice and between specialist units. The results of this research may provide the impetus for the development of clinical and research networks to enable the uniform delivery of health services benchmarked against international standards.

Isolation and identification of hydroxythiohomosildenafil in herbal dietary supplements sold as sexual performance enhancement products.

An unknown compound is detected and isolated from two herbal dietary supplements bought on the internet. The structure of the unknown compound is elucidated using ESI-MS/MS, NMR, UV and IR. The compound, named hydroxythiohomosildenafil, is identified as an analogue of sildenafil in which the oxygen atom is substituted with a sulfur atom in the pyrazolopyrimidine moiety, and a hydroxyethyl group instead of a methyl group is attached to the piperazinyl nitrogen. It is the first report of this compound being detected in herbal dietary supplements. The UV, IR and completely assigned NMR data of hydroxythiohomosildenafil is recorded.