Outcomes for Severe Complicated Clostridium difficile Infection Treated with Vancomycin Enemas

Abstract

Introduction: The prevalence of Clostridium difficile infection (CDI) is increasing. Serious, complicated infections have been linked to a virulent strain (BI/NAP1), which produces elevated levels of toxin and can lead to colectomy or death. For these infections, standard of care is now concomitant treatment with IV metronidazole (IVM) and per oral vancomycin (POV). Some institutions use add-on therapy with vancomycin per rectum (VPR) to increase colonic drug delivery when there is a concern about delayed transit. Our purpose was to look at clinical outcomes of consecutive patients with CDI treated with VPR at our hospital. Methods: Using pharmacy records and manual chart review, we identified inpatients prescribed VPR from 1/2003 to 12/2013. Included patients had diarrhea, a positive stool test for Clostridium difficile toxin by ELISA, and no alternative cause for symptoms. Patients were required to have been in the ICU at the initiation of treatment and to have received ≥4 doses of VPR. Patients were followed to discharge or death. Results: We identified 43 CDI patients who received VPR during the study period. We excluded 18 patients because they did not receive ≥4 doses of VPR and 1 patient who received VPR after colonic surgery. There were 11 males and 13 females, mean age was 61.8±15.9 years (range: 21-93). The dose of VPR (IV solution mixed in 100 cc of tap water) ranged from 125 to 250 mg Q 6-8 hrs. Most patients received concomitant therapy with POV (n=17) and/or IVM (n=20). Four patients (16.7%) underwent colectomy and 3 died post-op. Mortality was 11/24 (45.8%) including the 3 post-op deaths. The mean number of doses of VPR in those who survived versus died was 22.3±6.9 vs. 19.3±19.4 (P=0.62). Similarly, there were no significant differences (all P>0.05) in age (64.5±16.7 vs. 59.1±15.3 years), WBC (24.6±11.5 vs. 25.7±17.9K), or interval rise in creatinine (91.6% vs. 100%) between those who survived versus died or those who survived versus the combined endpoint of surgery/death. There was notably a shorter median time interval between initiation of CDI treatment and initiation of VPR for those who survived and avoided surgery (3.5 days; IQR 1-15.25 vs. 8.5 days; IQR 2-19.5), but this was not statistically significant (P=0.47). Conclusion: In our study, the largest case series reported to date on the use of VPR for severe, complicated CDI, 50.0% of patients ultimately died or had a colectomy. Based on our modest sample size and high rate of morbidity and mortality we cannot strongly advocate for the use of VPR at this time. It appeared that earlier initiation of VPR may be beneficial. Controlled trials are needed to better assess this therapy.