Prevalence of toxigenic C. difficile carriers on hospital admission
During the study period, 1,045 out of the 1,586 patients admitted to the Division of Infectious Diseases of our hospital were of older age (≥65 years). PCR screening for toxigenic C. difficile carriage was conducted for 628 (60.1%) out of these 1,045 patients (Fig. 1). PCR screening was not performed in the remaining 417 patients because stool samples or rectal swab specimens could not be collected within 48 hours of admission or the patient refused to provide rectal swabs or undergo a stool examination.
Of the 628 screened patients, 101 (16.1%) were toxigenic C. difficile carriers. The monthly prevalence of toxigenic C. difficile carriage at admission ranged from 4.0 to 15.9 per 10,000 patient-days, with an average of 8.8 per 10,000 patient-days during the study period (Fig. 2). The demographic and clinical characteristics of the screened patients are shown in Table 1. Of the 101 patients with positive PCR test results, 55 (54.5%) were diagnosed with symptomatic CDI (45 healthcare-associated and 10 community-acquired cases) and underwent antibiotic therapy for CDI. In particular, nine patients were diagnosed with symptomatic CDI at admission, and 24, including these patients, started CDI treatment within 48 hours of admission.
Construction of the clinical prediction model
Carriers of toxigenic C. difficile among our screened patients were more likely to reside in a facility than at home and be exposed to medical procedures 30 days before admission than those who were non-carriers (Table 1). Carriers had more neurological, chronic pulmonary, and connective tissue as well as hematologic diseases than non-carriers (Table 1). Only three patients with toxigenic C. difficile had a history of CDI 90 days before admission. Multidrug-resistant microorganisms, such as carbapenem-resistant Acinetobacter baumannii or methicillin-resistant Staphylococcus aureus were more commonly isolated from clinical samples during hospitalization in carriers than in non-carriers (Table 1).
In the multivariable logistic regression model, septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors were significant risk factors associated with toxigenic C. difficile carriage at the time of admission in older patients admitted to the Division of Infectious Diseases, Department of Internal Medicine (Table 2).
We calculated the predictive probability of patients being toxigenic C. difficile carriers using the following formula:
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)
A: If septic shock, positive = 1 / negative = 0; B: If connective tissue diseases, positive = 1 / negative = 0; C: If anemia, positive = 1 / negative = 0; D: If recent use of antibiotics, positive = 1 / negative = 0; and E: If recent use of proton-pump inhibitors, positive = 1 / negative = 0
When a cut-off value of ≥0.45 was applied to the clinical prediction model, the AUC value was 0.80, with a 95% confidence interval (CI) of 0.74–0.86 in the derivation cohort. The sensitivity, specificity, positive predictive value, and negative predictive value of this prediction rule were 75.3% (95% CI, 65.7–83.3), 74.3% (95% CI, 64.6–82.4), 74.5% (95% CI, 67.3–80.6), and 75.0% (95% CI: 67.7–81.1), respectively (Table 3). As shown in Table 3, the test and training data sets had similar accuracy, sensitivity, and specificity. The Hosmer–Lemeshow goodness-of-fit test result for the final model was P=0.58, yielding no evidence for a lack of fit.
Validation of the clinical prediction model
The validation cohort included 170 patients who underwent PCR screening upon admission for toxigenic C. difficile carriage between April 2021 and October 2021. PCR screening was not performed in 33 patients because stool samples or rectal swab specimens could not be collected within 48 hours of admission. This prediction risk model showed an AUC of 0.84 (95% CI, 0.78–0.90) in the validation dataset. The sensitivity, specificity, positive predictive value, and negative predictive value of this prediction rule were 78.3% (95% CI, 56.3–92.5), 70.75% (95% CI, 62.7–78.0), 29.5% (95% CI, 23.1–36.8), and 95.4% (95% CI, 90.5–97.8), respectively (Table 3). Of the 170 screened patients, 23 were positive for C. difficile toxin and 147 were negative. Our prediction rule confirmed that 27 were false positives and six were false negatives.