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A systematic review was conducted to explicitly identify interventions that alone, or in combination, were effective in improving antibiotic prescribing. The citation search strategy used in the present review provided a database of 365077 studies, of which only twenty-five were included in the final review (“review studies”). Analysis of the interventions used within the review studies indicated that a combination of “guidelines” and “pharmacy” interventions have the greatest potential to improve antibiotic prescribing. Two types of qualitative research were conducted, semi-structured interviews and the collection of naturally occurring data. Semi-structured interviews were conducted in order to determine NHS managers? perceptions of current policies used to improve antibiotic prescribing within selected Primary Care Trusts and highlighted the importance of pharmacy intervention, formularies or guidelines and improved prescribing analysis (IT based intervention) on improving antibiotic prescribing. This was supported by the collection of naturally occurring data, which was used to provide further insight into interventions used to improve antibiotic prescribing. The Specialist Antibiotic Pharmacist (HD) produced and implemented an innovative electronic antibiotic prescribing analysis tool (the Antibiotic Database) to analyse and improve antibiotic prescribing in a consistent manner. The key advantage of the Antibiotic Database was the time and money saved on producing visual electronic outputs containing an inaccurate outcome measure or time period for analysis. The results concluded that an IT based intervention, such as the Antibiotic Database should be used, in addition to the use of antibiotic guidelines and pharmacy intervention, within all sectors of the NHS in order to improve antibiotic prescribing and its analysis.

Fluoroquinolones are amongst the most effective antimicrobials used to treat infectious diseases caused by members of the Enterobacteriaceae. The rapid spread of fluoroquinolone resistant Enterobacteriaceae threatens the future effectiveness of this widely used group of antimicrobial compounds. Fluoroquinolone resistance in Enterobacteriaceae in Vietnam highlights an approaching crisis in antimicrobial therapy of Enterobacteriaceae infections as fluoroquinolone resistant infections may require expensive alternative treatments. Furthermore, a lack of alternative drugs for treating fluoroquinolone resistant bacteria also contributes to the difficulty in treating such infections. The aim of this study was to investigate the prevalence and mechanisms of fluoroquinolone resistance in commensal Enterobacteriaceae isolated from two different populations resident in Ho Chi Minh City; hospitalized patients and healthy volunteers. I investigated the prevalence of mutations in the DNA gyrase and the topoisomerase gene, the target of the fluoroquinolones and the main resistance mechanisms in Enterobacteriaceae. Additionally, I investigated the spectrum of plasmid-mediated quinolone resistance (PMQR) determinants, a more contemporary mechanism of fluoroquinolone resistance. By using whole plasmid sequencing, bioinformatics and a miniaturized DNA nanoarray, an association of PMQR determinants with other antimicrobial resistance genes including blaLAP_2, which confers resistance to ~-lactam antimicrobials, was found. Moreover, diverse patterns of antimicrobial resistance between isolates from hospital and community populations were revealed. An increase in the quantity ofPMQR determinants isolated from rectal swabs of children treated with antimicrobials was also demonstrated using a gene specific real-time PCR. I surmise that variety antimicrobial classes might contribute to an increase in copy number and eo- selection of PMQR determinants in Ho Chi Minh City. Fluoroquinolone resistance in Enterobacteriaceae has increased oyer time and this class of antimicrobial is still commonly used, to treat infection caused by such organisms. Understanding fluoroquinolone resistance mechanisms and their relationship to other antimicrobial resistance mechanisms in Enterobacteriaceae should play an important role in the control of the spread of antimicrobial resistance genes and aid treatment strategies for clinicians in Vietnam.

A survey of 48 isolates of the entomopathogenic fungus Metarhizium anisopliae for production of the anti-cancer indolizidine alkaloid swainsonine revealed that 55% of the strains of the haploid variety anisopliae produced swainsonine as did 30% of the strains of the diploid variety majus. There was no evidence of either geographical restriction of producer strains or of any host preference. Only two isolates of M anisopliae vaL anisopliae produced high concentrations of swain so nine in submerged liquid culture and one of these (lMl 147690) was used to investigate the physiology of swainsonine production in shake flask cultures and 3.5 litre fermentations. Conditions were optimised and the process was scaled up to production from a 400 litre fermentation that was estimated to have produced over 30g of swainsonine after 87 hours. A simple and efficient isolation process was developed to purify swainsonine from the fermentation broth and despite minor technical problems during the isolation, the final yield of 10.36g was considerably higher than previously reported from other fermentations of this species. These improvements could be commercially important should this currently expensive alkaloid progress further through clinical trials. Swainsonine was also shown for the first time to be produced by M. anisopfiae during insect parasitism. Analysis oflepidopteran larvae artificially infected with isolate IMI 147 690 showed the presence of other polyhydroxylated alkaloids which appear to be novel natural products from tentative identification. These seem to be related biosynthetically to swainsonine. Some aspects of the biological activity of swainsonine were also investigated and it was found that it did not inhibit the growth of a range of saprophytic fungi and bacteria but it was effective against several species of plant-parasitic nematodes both in vitro and in vivo. It displayed systemic activity after foliar application and persisted in the tissues of tomato plants for over 5 weeks with no apparent phytotoxicity.