Risk factors for Clostridium difficile colonisation and toxin production.

OBJECTIVES: to examine risk factors for patients becoming Clostridium difficile culture and toxin positive. DESIGN: prospective cohort study. SETTING: two medicine for the elderly wards. PARTICIPANTS: patients admitted to the wards over a 17-month period. MEASUREMENT: presence of Clostridium difficile on culture of stool specimens and toxins A and/or B. Patient's age, sex, source of admission, antibiotic, laxative, antacid and steroid use, presence/absence of colonic disease, neoplasia, leukaemia and nasogastric or percutaneous endoscopic gastrostomy tube feeding. RESULTS: 390 of 865 patients admitted provided a total of 1003 faecal specimens. Age (OR 1.04, 95% CI 1.001-1.07 per year), admission from another hospital (OR 2.13, 95% CI 1.29-3.50), non-cephalosporin antibiotics (OR 2.08, 95% CI 1.25-3.46) and cephalosporin use (OR 8.45, 95% CI 2.99-23.9) increased risk of becoming Clostridium difficile culture positive. Becoming toxin-positive was associated with antibiotic use only (OR 3.02, 95% CI 1.15-7.92), specifically amoxycillin (OR 8.72, 95% CI 1.66-45.9) and cephalosporins other than ceftriaxone (OR 7.28, 95% CI 1.34-39.6). CONCLUSION: different risk factors are important for the two stages leading to Clostridium difficile diarrhoea. Age, source of admission and third generation cephalosporins increase risk of becoming culture positive, whilst only antibiotic use is associated with the step of becoming toxin-positive. Understanding these differential risks may aid infection control strategies.

Clostridium difficile in a geriatric unit: a prospective epidemiological study employing a novel S-layer typing method.

Clostridium difficile is the major identifiable cause of antibiotic-associated diarrhoea in the UK. The aim of this study was to employ traditional culture, toxin detection and a novel typing method to determine the level of C. difficile colonization and disease in a population of elderly patients and to investigate the association between strains in the patients and their environment. Three hundred and ninety patients between 62 and 101 years of age admitted to a geriatric unit in the Royal Victoria Hospital (RVH), Edinburgh, were investigated for the presence of C. difficile. C. difficile was cultured from 100 (26 %) patients using pre-reduced cycloserine-cefoxitin egg yolk agar, and toxin(s) was detected in the faeces of 34 of these patients using the Techlab ELISA test kit for the detection of C. difficile toxins A and/or B. Toxin(s) was detected in a further 18 patients from whom no C. difficile was detected in culture. Of the patients in whom C. difficile was detected, 49 % had diarrhoea, with the highest proportion of patients with diarrhoea being both culture- and toxin-positive for C. difficile. Environmental sampling of the patient environment yielded C. difficile from 14 % of samples. The organism was most frequently isolated from floors, sluice-rooms and toilet areas. The variation in the molecular mass of the C. difficile S-layer proteins was exploited as the basis of a novel typing method for C. difficile. Isolates from patients in the RVH were given a four-digit 'S-type' number based on their S-layer protein profile. A total of seven S-types were identified, with one type, toxigenic S-type 5236, accounting for 73 % of all clinical isolates and 91 % of environmental isolates.

Changes in sensitivity patterns to selected antibiotics in Clostridium difficile in geriatric in-patients over an 18-month period.

Clostridium difficile-associated disease continues to be a major problem in hospitals and long-term care facilities throughout the developed world. Administration of certain antibiotics such as amoxycillin, oral cephalosporins and clindamycin is associated with the greatest risk of developing C. difficile disease. The two antibiotics used for treatment of C. difficile disease are vancomycin and metronidazole, to which there is currently very little resistance. Randomly selected isolates (186) from 90 patients being investigated during an 18-month epidemiological study into the disease were tested for their susceptibility to vancomycin, metronidazole, amoxycillin, clindamycin, cefoxitin and ceftriaxone by the NCCLS agar dilution method. There was a narrow range of MIC for the two treatment agents (vancomycin and metronidazole), from 0.5 to 4 microg ml(-1), with no evidence of resistance. All strains were resistant to cefoxitin (MIC 64-256 microg ml(-1)), the antibiotic used in most selective media. All strains were of similar sensitivity to amoxycillin (MIC(90)= 4 microg ml(-1)). Most strains were resistant to ceftriaxone (MIC > or = 64 microg ml(-1)) or of intermediate resistance (MIC > or = 32 microg ml(-1)), with only two sensitive strains (MIC 16 microg ml(-1)). Clindamycin resistance was common, with 67 % of strains resistant (MIC > or = 8 microg ml(-1)), 25 % with intermediate resistance (MIC > or = 4 microg ml(-1)) and only 8 % sensitive (MIC < or = 2 microg ml(-1)). Twelve isolates from six different patients had very high resistance to clindamycin (MIC > or = 128 microg ml(-1)). 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 appeared to become more resistant while others became less resistant. No differences were seen in the MIC(50) and MIC(90) of the different S-types of C. difficile identified, although some S-types were present in very small numbers. There was no correlation between the antibiotics prescribed and susceptibility.