A total of 1721 new cases of CDAD were identified during the 13-year study period, 1658 (96.3%) of which had a positive cytotoxin assay result. Of those without a positive cytotoxin assay result, 59 had endoscopic changes typical of pseudomembranous colitis, and 4 were diagnosed on histopathological grounds. shows the incidence of CDAD among residents of Sherbrooke during the study period. The annual incidence increased from 35.6 per 100 000 population in 1991 to 156.3 per 100 000 in 2003. Among residents in the Estrie region outside of Sherbrooke, the incidence remained stable from 1991 to 2002 (22.2 and 25.2 per 100 000 respectively) and increased in 2003 (92.2 per 100 000); however, incidence rates are probably underestimated, since referral of cases and specimens was incomplete and may have changed over time. Age-specific incidence rates in Sherbrooke are also shown in . The incidence among children decreased after 1996, when the cytotoxin assay had to be specifically requested. Among people aged 18–64 years, the incidence increased only in 2003. Among people aged 65 years or more, the annual incidence increased 10-fold during the study period, up to 866.5 cases per 100 000 in 2003; the incidence was 1681 per 100 000 among those aged 80 years or more.
The case-fatality rate and the proportion of cases that were considered complicated more than doubled over time, as measured among the 1675 new cases for whom enough information was available to assess these outcomes (). The absolute number of patients who had megacolon, perforation or shock requiring vasopressor therapy, who needed a colectomy or who died within 30 days after diagnosis of CDAD increased dramatically, from 6–10 such cases per year during 1991–1998 to 71 cases in 2003. After adjustment for age, sex, initial treatment of CDAD, immune status, and tube feeding and surgery in the 2 months preceding diagnosis, cases diagnosed in 2003 had a higher likelihood of having complicated CDAD than those diagnosed in previous years. In these models, the peak leukocyte counts and creatinine levels were not included because these parameters are clearly on the causal pathway between year of diagnosis and the outcomes.
From 1991 to 2002 the proportion of cases in which complicated CDAD developed and the proportion of cases in which death occurred within 30 days after diagnosis were 25.4% (68/268) and 19.0% (51/268) respectively among patients with a high leukocyte count (20.0 х 109/L or greater), an elevated creatinine level (200 μmol/L or greater) or both. The corresponding proportions among patients with lower leukocyte counts and creatinine levels were 6.0% (40/666) and 4.2% (28/666). In 2003, the proportion of cases with complicated CDAD and the proportion of cases in which death occurred within 30 days after diagnosis increased, both among patients with high leukocyte counts, creatinine levels or both (40.9% [45/110] and 25.5% [28/110] respectively) and among those with lower leukocyte counts and creatinine levels (12.3% [25/204] and 11.3% [23/204] respectively). In 2003, of the 110 patients with high leukocyte counts, creatinine levels, or both, 87 were initially given metronidazole; complicated CDAD developed in 34 (39.1%) of them, including 20 (23.0%) who died within 30 days after diagnosis. Only 2 such patients were initially given vancomycin, none of whom had complicated CDAD.
Factors associated with complicated CDAD, in univariate and multivariate analyses, are shown in . The population for these analyses included inpatients of the CHUS and the outpatients for whom enough information was available to assess whether they had complicated CDAD. Sex and fever were no longer significant in the multivariate analysis. The independent factors associated with complicated CDAD were age of 65 years or more, hospital-acquired CDAD, tube feeding in the 2 months preceding diagnosis, not having had surgery in the 2 months preceding diagnosis, immunosuppression, a peak leukocyte count of 20.0 х 109/L or greater and renal failure. After adjusting for these confounding factors, initial treatment with vancomycin was associated with a 79% lower risk of complicated CDAD compared with initial treatment with metronidazole (adjusted odds ratio 0.2, 95% confidence interval 0.06–0.8, p = 0.02). In contrast, initial treatment with metronidazole was not associated with a more favourable outcome compared with no treatment. In these models, which attempted to document short-term correlates of adverse outcomes, peak leukocyte count and creatinine level were included, and year of diagnosis was no longer found to enhance significantly the fit of the models, because part of the enhanced severity of CDAD in recent years was captured by leukocyte count and creatinine level.
shows the variations over time in the distribution of antibiotics that seemed to provoke CDAD among 1364 patients (515 with community-acquired CDAD and 849 with hospital-acquired infection) for whom information was available on the use of antibiotics in the 2 months preceding diagnosis. Overall, more than two-thirds of the CDAD cases had received cephalosporins in the 2 months before diagnosis. The proportion of patients who had received quinolones increased progressively, up to 55% in 2003, whereas the proportion who had received aminoglycosides decreased. This might to some extent reflect changes in patterns of use of antimicrobial agents and in the distribution of hospital- versus community-acquired cases. Thus, in we show the rate of hospital-acquired CDAD per 1000 patient-days of antibiotic use among all CHUS inpatients. For the calculation of this rate, the numerator corresponds to the number of CHUS patients (regardless of city of residence) with hospital-acquired CDAD who received a given class of antibiotic in the 2 months before diagnosis, and the denominator corresponds to the number of patient-days that this class of antibiotic was used among all CHUS inpatients during these years. Compared with the rates in 1999– 2002, the rate in 2003 was higher for all classes of antibiotics except cotrimoxazole. Antibiotics associated with the highest risk of CDAD were macrolides, third- and second-generation cephalosporins, clindamycin and quinolones.