[Truncated abstract] The prinicipal aim of this thesis was to explore the relationship between 3rd generation cephalosporin antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea (CDAD). This antibiotic class has been implicated in the aetiology of CDAD; therefore restriction of these antibiotics via antibiotic policies represents a potential strategy for prevention and control of CDAD. Successful control of CDAD in hospitals translates to improved quality of care for patients, and a reduction of pressure on hospital resources. Therefore, the objectives of this study were to determine whether 3rd generation cephalosporins were related to CDAD, to evaluate the effect of changes to antibiotic policy on the incidence of CDAD, and to determine the impact of CDAD on patient length of stay and hospital costs. The study was conducted in Sir Charles Gairdner Hospital (SCGH), a public teaching hospital located in Perth, the capital city of the state of Western Australia. Evidence for an association between 3rd generation cephalosporins and CDAD was obtained from studies of ecologic- and individual-level data. A time series analysis of the relationship between monthly consumption of 3rd generation cephalosporins and the incidence of CDAD in SCGH was undertaken covering the period 1994 to 2000. The results demonstrated a positive relationship between the use of 3rd generation cephalosporins and CDAD. A matched case-control study that involved 193 adult inpatients diagnosed with CDAD and 386 adult inpatients without CDAD, selected from the period 1996 to 2000, was conducted. Information was collected on exposure to 3rd generation cephalosporin antibiotics during hospitalisation, as well as exposure to other antibiotics and medications, procedures, and comorbidities. Results from conditional logistic regression analyses found CDAD cases were six times more likely to be exposed to 3rd generation cephalosporins during their admission, prior to the onset of diarrhoea, than controls (adjusted odds ratio [OR] = 6.17, 95% confidence interval [CI] = 1.56-24.37). Approximately one third of CDAD in the study population could be attributed to 3rd generation cephalosporins. CDAD cases were also four times more likely to have been exposed to either amoxicillin-clavulanate or ticarcillin-clavulanate (adjusted OR=4.23, 95% CI=1.81-9.93). In October 1998, an antibiotic policy was introduced at SCGH that restricted the use of ceftriaxone, the 3rd generation cephalosporin most commonly used by the hospital. During 1999 and 2000, the incidence of CDAD halved as ceftriaxone consumption fell in response to this policy. The effect of this policy was demonstrated in the time series model; during the post-policy period the relationship between ceftriaxone and CDAD that was evident prior to the policy was cancelled out. From the individual-level data, obtained from the case-control study, a reduction in the prevalence of exposure to 3rd generation cephalosporins from 11% to 1% accounted for a 30% reduction in the incidence of CDAD. Data from the case-control study was also used to analyse the independent contribution of CDAD to length of stay and admission costs using multiple linear regression