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Mechanisms and pharmacodynamics of antifungal agents for cryptococcal meningitis. (360G-Wellcome-209714_Z_17_Z)

Cryptococcal meningitis (CM) is an infection of the brain and surrounding tissues (the meninges). It is caused by a yeast called Cryptococcus and is responsible for approximately 180,000 deaths annually (26). The most effective drug is amphotericin B (AmB) which needs to be given for 2 weeks and causes dangerous side-effects. A modified formulation, liposomal amphotericin B (LAmB), may be easier to administer to patients because it can be given as a single dose, and appears to be as effective as 2-weeks of conventional AmB (12, 15, 23). This observation raises a number of questions: 1) What is the optimal dosing strategy for LAmB? I will measure drug levels and describe their relationship with reduction in Cryptococcus levels. 2) How does one dose of LAmB exert a prolonged effect? i will image the movement of LAmB in mouse brains and meninges to assess how long LAmB stays in these regions. During treatment for CM, the rate of decline of yeast in spinal fluid is highly variable (24, 25, 27). Therefore, another question is: 3) Do different groups of yeast vary in teir response to treatment? I will collect samples of Cryptococcus and characterise their survival ability in various conditions.

£0

30 Sep 2018

Grant details
Amount Awarded 0
Applicant Surname Stott
Approval Committee Internal Decision Panel
Award Date 2018-09-30T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title PhD Training Fellowship for Clinicians
Internal ID 209714/Z/17/Z
Lead Applicant Dr Katharine Stott
Planned Dates: End Date 2020-08-31T00:00:00+00:00
Planned Dates: Start Date 2017-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region North West
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