| Summary: | Central nervous system (CNS) infection remains a major cause of mortality and morbidity worlwide. This thesis focuses on the causes, prognostic markers, and pathogenesis of meningitis in adults in Viet Nam and explores the pharmacokinetic properties of fluoroquinolones in the treatment of tuberculous meningitis (TBM). Chapter One provides an introduction to infections of the CNS in Viet Nam. Chapter Two describes the clinical studies of CNS infections at the Hospital for Tropical Diseases in Viet Nam which underpin this thesis. Mycobacterium tuberculosis is the most common cause of CNS infections with the three commonest causes of acute pyogenic meningitis Streptococcus suis, Streptococcus pneumoniae and Neisseria meningitidis. In Chapter Three, I report on a study of the pathogenesis of meningitis and encephalitis in particular the role for Metalloproteinase/Tissue Inhibitor of Metalloproteinase. One of the most challenging situations is to distinguish partially treated pyogenic meningitis from TBM and viral meningitis and encephalitis. I identified two major clinical factors that can help distinguish TBM from pyogenic meningitis- gingivo-herpes and deafness are very much more common in pyogenic meningitis than in TBM (Odds Ratio 32). In Chapter Four, I develop a clinical aligorithm and in Chapter Five, a prognostic system to determine which variables can be used to predict the clinical outcome.TBM remains very difficult to treat. In Chapter Six, I report the results of a pharmacokinetic study aimed to identify the optimal fluoroquinolone to be used for the treatment of TBM. My results demonstrate levofloxacin has a better pharmacokinetic profile than ciprofloxacin or gatifloxacin for the treatment of TBM.
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