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Title: Antibiotics and Clostridium difficile
Author: Caproni, Lisa J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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The aims of this thesis were to investigate the antibiotic susceptibility patterns of C. difficile with relation to the S-type of the isolates over a period of 18 months. Detailed growth curves were performed on strains NCTC 11223, the sequenced strain 630 and an endemic isolate 338a. Toxin A was shown to be produced upon entry to stationary phase in agreement with other studies. OD600 was found to be a good predictor of growth phase and allowed this measurement to be used for subsequent experiments. MICs were performed on 186 random isolates of C. difficile collected during an 18-month epidemiological study to investigate the patterns of sensitivity to six different antibiotics. No evidence of resistance was seen to the two treatment antibiotics and all strains were resistant to cefoxitin (MICs 64-256mg/ml), the antibiotic used in most selective media. Most strains (98.9%) had intermediate resistance to ceftriaxone. The MIC50 and MIC90 of the strains to amoxicillin and clindamycin were very close (8 and 16 for amoxicillin and 16 for clindamycin) but the range of MICs was great. Clindamycin resistance was common with 67% of strains resistant (MICs of > 8mg/ml), 25% with intermediate resistance (MIC > 4mg/ml) and only 8% sensitive (MICs of < 2mg/ml). Twelve isolates from six different patients had very high resistance to clindamycin with MICs > 128mg/ml. Multiple isolates from the same patient, taken at different times, showed changes in susceptibility patterns over time. The only major change in susceptibility over the time period was in clindamycin resistance; some strains appearing to become more resistant while others became less resistant. No differences were apparent in the MIC50 and MIC90 of the different S-types of C. difficile identified, although some S-types were present in very small numbers. No links between antibiotics prescribed and susceptibility patterns were found. Three strains (NCTC 11223, strain 630 and endemic isolate 338a) were cultured in sub-lethal concentrations of the six antibiotics (1/2,1/4 and1/8 of the MIC) over 104 hours and growth and toxin A measured three times a day. The effects varied between strain and antibiotic. The most common effect on the growth of the strains was to increase the initial lag period by ca. 4h compared to the antibiotic-free controls through the clindamycin resistant strain NCTC 11223, (MIC >512mg/ml) showed not lag whatsoever in comparison to the controls when grown in this antibiotic. The most common effect on toxin A production was in the onset of toxin elaboration. Normally toxin began to appear in low levels in early stationary phase before accumulating to high levels by the start of decline.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available