Methicillin resistant Staphylococcus aureus (MRSA) is the resistant subpopulation of the bacteria S. aureus that causes a large number of hospital-associated infections worldwide. These infections could be prevented if the mechanisms of transmission and isolate or clonal success were understood. The work presented in this thesis aims to link experimental measures of fitness (biological success) with mathematical models of clinical populations to generate insights into what makes a successful clone and thereby suggest novel infection control measures. Using a new experimental fitness assay it was shown that carriage of large antibiotic resistance plasmids had little effect on fitness, but that lineage and clonal background did. This implies antibiotic resistances are likely to be maintained long term and that CC22 SCCmecIV may be the dominant MRSA clone in the UK as it is the fittest. In the light of these differences, and in an epidemiological study using data from a UK hospital (St George’s Healthcare NHS Trust), three novel reasons for clonal success are suggested: high relative fitness, flexibility of resistance carriage and resistance to fluoroquinolones. The importance of these to clonal dynamics was confirmed in a deterministic model of clonal populations. The reasons for clonal success also generated a hypothesis that use of ciprofloxacin (a fluoroquinolone) was responsible for maintaining MRSA populations. This was tested, and the magnitude of the effect, compared to other infection control methods, estimated in a new stochastic model of MRSA transmission. In conclusion, due to the small fitness costs associated with antibiotic resistance carriage, a general decline in antibiotic use may not restore susceptibility. However, using a better understanding of near universal ciprofloxacin resistance, a new infection control method is proposed: decreased use of this antibiotic will decrease the main selective pressure on MRSA populations and lead to a decline in infection incidence.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:625907 |
| Date | January 2012 |
| Creators | Knight, G. M. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1364855/ |
Page generated in 0.0018 seconds