Spotlight on Clostridioides difficile infection

Recent research on Clostridioides difficile infection found changing trends in infection rates at Veterans Health Administration hospitals and questioned common practices with regard to treatment.

Clostridioides difficile infection was the focus of three recent studies, which found that infection rates have decreased in recent years, that patients with inflammatory bowel disease (IBD) may benefit from longer duration of vancomycin therapy, and that dual therapy with IV metronidazole and oral vancomycin may not necessarily improve outcomes.

In the first study, researchers used a Veterans Health Administration (VA) database to assess temporal trends in C. difficile infection from Jan. 1, 2006, to Dec. 31, 2016. The retrospective cohort study included 472,346 adults who had stool testing for C. difficile at 119 acute care hospitals within the continental United States. A case of C. difficile infection was defined as any stool that tested positive for C. difficile via assay or culture, and lab tests with results that were indeterminate, canceled, or incomprehensible (null result) were excluded. Community-acquired and community-onset health care facility-associated C. difficile infection data were also excluded. Results were published online on Nov. 11 by Infection Control & Hospital Epidemiology.

Overall, 68,995 new cases of C. difficile infection were included in the incidence analysis. The incidence of total inpatient C. difficile per 10,000 patient-days decreased from 16.81 in 2006 to 13.63 in 2010. There was a brief increase to 15.23 in 2011, which was linked to the increased use of molecular testing within the VA in 2010 (P<0.0001). After that, C. difficile infection incidence gradually decreased again from 14.77 in 2012 to 13.66 in 2016. During the study period, the incidence of hospital-onset and health care facility-associated C. difficile infection also decreased from 10.87 to 6.41 per 10,000 patient-days. The overall crude 30-day mortality of patients with C. difficile infection decreased from 2.17 deaths per 10,000 patient-days in 2006 to 1.41 in 2016.

Coordinated antimicrobial stewardship efforts at the VA began in 2011 and led to decreases in antibiotic use. Decreased use of fluoroquinolones (P<0.0001), clindamycin (P=0.0006), and third-generation cephalosporins (P=0.0002) correlated with decreased rates of C. difficile infection. However, VA mandatory reporting of hospital-acquired C. difficile infection, which was implemented in 2012, did not influence C. difficile infection rates (P=0.24). Limitations of the study were its retrospective design and the fact that it included only records within VA hospitals, the authors said.

The other two studies focused on treatment of C. difficile infection. In one study of 134 patients with IBD (median age, 29 years; ulcerative colitis, n=57; Crohn's disease, n=77), researchers compared rates of C. difficile infection recurrence and re-infection in those receiving long-duration (n=57) versus short-duration (n=77) oral vancomycin therapy, defined as 21 to 42 days and 10 to 14 days, respectively. Recurrence and re-infection were defined as positive C. difficile toxin assay by polymerase chain reaction (PCR) within or after eight weeks of the end of antibiotic therapy, respectively. Results were published online on Nov. 7 by the American Journal of Gastroenterology.

Patients receiving long-duration vancomycin had a 1.8% incidence of C. difficile recurrence, compared with 11.7% in the short-duration group (odds ratio [OR], 0.13; P=0.043). Multivariate logistic regression models showed that patients treated with long-duration vancomycin had lower odds for recurrence than those who received short-duration vancomycin (OR, 0.03; P=0.021). However, C. difficile re-infection rates and time to re-infection were not significantly different between groups (14.0% with long-duration vs. 16.9% with short-duration; P=0.81).

The study was limited by its retrospective design and small cohort, the authors noted. “This study suggests that prescribing a longer duration of vancomycin for initial [C. difficile infection] in patients with IBD may be more effective at preventing recurrence than the current practice,” they concluded. “However, this strategy should also be considered from both cost-effectiveness and public health perspectives.”

The third and final study looked at whether dual therapy with IV metronidazole and oral vancomycin was associated with improved outcomes in patients with C. difficile infection compared to oral vancomycin alone. Researchers retrospectively assessed adults hospitalized in two centers from 2010 to 2018 who had a positive C. difficile PCR performed on an unformed stool and received oral vancomycin within two days of testing. The primary outcome was death or colectomy within 90 days after the index test. Results were published online on Nov. 12 by Clinical Infectious Diseases.

A total of 2,114 patients received dual therapy (n=993) or monotherapy (n=1,121), and 23% met the primary outcome. There was no association between dual therapy and death or colectomy within 90 days (adjusted OR, 1.07; 95% CI 0.79 to 1.45), even when the analysis was restricted to patients with fulminant C. difficile infection (adjusted OR, 1.17; 95% CI, 0.65 to 2.10). There was also no association between dual therapy and C. difficile infection recurrence.

The study's main limitations were its retrospective design and the potential for residual confounding, the authors said. They noted that guidelines from the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America currently recommend dual therapy for fulminant C. difficile infection. “The recommendation that IV metronidazole be added to oral vancomycin in patients with fulminant [C. difficile infection] merits re-consideration,” they concluded.