CHICAGO – Initial vancomycin monotherapy was associated with significantly higher rates of subsequent Clostridium difficile infection among 101 patients with inflammatory bowel disease in a retrospective observational study.
The rate of C. difficile infection (CDI) recurrence over the following year was 39.4% for patients initially treated with vancomycin (Vancocin), 14.5% for patients treated with metronidazole (Flagyl), and 13.3% for those given combination metronidazole and vancomycin. The difference was statistically significant between vancomycin and both metronidazole and combination therapy (P less than .05 for both), lead author Dr. Amar Naik said at the annual Digestive Disease Week.
No significant differences were found between groups in terms of disease duration or inflammatory bowel disease (IBD) maintenance therapy. There were 48 metronidazole patients, 38 vancomycin patients, and 15 combination patients, and each treatment group comprised almost equal numbers of men and women.
The cohort included 62 patients with Crohn’s disease and 39 patients with ulcerative colitis who were followed at a single IBD center. A total of 89% were on maintenance immunosuppression for their IBD. The overall CDI recurrence rate was 24% (24 patients), with a mean time to recurrence of 6 months.
Of the 24 patients with CDI recurrence, 7 (29%) were women and 17 (71%) were men.
Patients initially diagnosed as inpatients were also less likely to experience recurrence than were those diagnosed as outpatients, but this difference did not reach statistical significance (17% vs. 27%), he said.
Steroid use within 3 months of CDI was significantly associated with a higher recurrence rate, compared with no steroid use (32% vs. 15.7%, P less than .05), said Dr. Naik, a gastroenterologist with the Medical College of Wisconsin in Milwaukee.
In a multivariate analysis, the only two significant predictors of CDI recurrence were initial vancomycin monotherapy (odds ratio 7.45, P = .04) and female gender (OR 0.26, P = .02).
"Combination therapy with metronidazole and vancomycin in IBD immunosuppressed patients with C. difficile infection might be more efficacious at preventing CDI recurrence over the following year," Dr. Naik said.
During a discussion of the study, an attendee asked whether there is something about vancomycin that makes CDI recurrence more likely or whether severity may have played a role in the findings.
Dr. Naik replied that there may be an IBD disease severity issue, but also that vancomycin has a profound impact on the gut microbiome. He went on to say that after CDI treatment, there may also be increased rates of vancomycin-resistant enterococcus infection, which could potentially affect the microbiome.
The latest Ontario Ministry of Health report cites a sharp increase in the number of confirmed cases of vancomycin-resistant enterococcus, from 834 in 2006 to 1,154 in 2009, the latest year for which figures were available. At the same time, the rate of CDI dropped from 4,536 to 3,266, although CDI-related diarrhea caused 478 deaths in 2009. In a study cited by Dr. Naik, vancomycin was shown to be superior to metronidazole in treating patients with severe CDI-associated diarrhea (Clin. Infect. Dis. 2007;45:302-7).
Initial antibiotic treatment in the current study included a 14-day course of metronidazole 250 mg t.i.d., or vancomycin 250 mg q.i.d., or metronidazole 250 mg t.i.d. plus vancomycin 250 mg q.i.d..
Initial CDI was confirmed based on symptoms, positive ELISA toxin A/B testing, or a positive nucleic acid amplification test (NAAT). Subsequent CDI was identified according to symptom recurrence and a positive toxin A/B or NAAT test.
Finally, an attendee noted that there have been anecdotal recommendations from some of Dr. Naik’s colleagues to use vancomycin as first choice for CDI treatment, and asked whether the study findings have changed practice at the Medical College of Wisconsin. Dr. Naik said further prospective studies are needed before changing clinical practice, but added, "This actually shows [that] some caution is needed." When pressed as to what he prescribes for his patients, he said that for inpatients, combination therapy with vancomycin and metronidazole should be considered.
Dr. Naik and his coauthors reported no conflicts of interest.