Nimish Patel, PharmD, PhD, describes his study, which compared fidaxomicin with oral vancomycin in early targeted therapy of C diff.
Segment Description: Nimish Patel, PharmD, PhD, associate professor of pharmacy practice, Albany College of Pharmacy and Health Sciences, describes his study, which compared fidaxomicin with vancomycin in early targeted therapy of C diff.
Interview transcript (modified slightly for readability):
“The study that I did was at the Upstate New York Veterans Health care Administration; that comprises 5 hospitals in Upstate New York: Albany, Bath, Canandaigua, Syracuse, and Buffalo. Because we know that Clostridium difficile infection (C diff) is associated with considerable morbidity, mortality, and health care expenditures, we wanted to look at fidaxomicin versus oral vancomycin, particularly when used as early targeted therapy.
We performed a retrospective cohort study and we included patients who are adults who received either oral fidaxomicin or oral vancomycin within the first 5 days—and that’s really the threshold we used to define early targeted therapy—for at least 48 hours, and started therapy as an inpatient.
They had to have a positive stool sample for C diff and in addition to that, they also had to have symptoms consistent with C diff—more than 3 loose stools within the preceding 24 hours or an ileus—and all other causes of diarrhea ruled out.
Within the study, we had manually collected data from patient’s medical records—demographics, co-morbid conditions, prior antibiotic exposures, their current course of hospitalization, antibiotic history—and the most important part of this, what we were trying to examine and compare, were the outcomes. The outcomes that we were interested in were vital status at 30 days and 60 days post-positive stool sample, and then recurrence after 60 days of completing therapy.
We also looked at total hospital length of stay, given the enormous health care expenditures associated with C diff infections and then we looked at a composite outcome that included both 60-day mortality as well as 60-day recurrence.
We had roughly 195 patients who received oral vancomycin and we had 95 patients who received fidaxomicin. When doing these retrospective studies, given the non-randomized nature of the study design, it’s really, really important to make sure that the groups are balanced.
Overall, the groups appeared to be balanced with respect to most of the covariates, although there were some that seemed to be disproportionate between vancomycin recipients and fidaxomicin recipients, specifically, the components of the Heinz VA severity index, which is a measure of C diff disease severity.
The bottom line is that patients who are on vancomycin appear to have a slightly higher disease severity than patients on fidaxomicin, and that will be important to consider when interpreting our findings.
We did observe a significant difference in hospital length of stay, so certainly, an enormous impact for cost effectiveness as well. When we looked at our individual outcomes of 30-day, 60-day mortality as well as 60-day recurrence, while proportionally they appear to have different proportions of those outcomes, statistically they were not different.
It wasn’t until we looked at our composite outcome which included 60-day mortality and 60-day recurrence where we saw a significant difference between fidaxomicin and oral vancomycin, favoring fidaxomicin. Keep in mind, at baseline when we compared our 2 treatment groups, they did appear to have some subtle differences with respect to disease severity.
We performed a multivariate analysis to control for that and adjust for disease severity. And even after adjusting for disease severity, C diff treatment, specifically vancomycin, was associated with the outcomes that we were evaluating—specifically 60-day recurrence and 60-day mortality as a composite outcome.
We also looked at out outcomes in specific sub-populations that we know are just at a higher risk for achieving poor outcomes. In those patients in the intensive care unit we saw a consistent trend as well as those patients who are above the age of 75.”