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.

An economic argument in favour of endoscopic third ventriculostomy as a treatment for obstructive hydrocephalus.

This project was undertaken to examine the health resource implications of performing endoscopic third ventriculostomy as an alternative to CSF shunting in appropriate patients. We carried out a retrospective study of case records and X-rays of patients shunted de novo at the INS, Glasgow for the two year period 1990-1991. We identified all those patients who would have been suitable for endoscopic third ventriculostomy and examined the shunt complications and extra days in hospital required by these patients. A total of 150 new shunts was inserted during the two year period. Of these, 23 patients (15%)were judged suitable for endoscopic third ventriculostomy as an alternative to CSF shunting. Eight out of 23 patients required a total of 29 repeat operations and an extra 230 days in hospital due to shunt complications. Assuming an 80% success (shunt free) rate for endoscopic third ventriculostomy, we calculate that 9 operations and 74 bed days per year could be saved by using this technique. We conclude that in units undertaking a large number of CSF shunt insertions, investment in neuroendoscopic equipment, training, and expertise has the potential to release significant resources for other uses.