Alison Lew, PharmD: Vancomycin Prophylaxis for CDI Recurrence

Segment Description: Alison Lew, PharmD, PGY2 Infectious Diseases Pharmacy Resident, University of Michigan, spoke about her research on oral vancomycin prophylaxis to reduce CDI recurrence.

Interview transcript (modified slightly for readability):

Prior retrospective studies cast a fairly broad net and evaluated all hospitalized patients who had any history of CDI and were started on systemic antibiotics. [The studies] didn't really carve out patients who are at higher risk of CDI, and so we were trying to better target that patient population.

So, I think that oral vancomycin is worth exploring because we know that CDI is associated with significant morbidity and mortality and we're always trying to figure out different ways to reduce CDI. So, looking at reducing acid-suppressive medications and antibiotics that are associated with a higher risk of CDI such as clindamycin and fluoroquinolones and just trying to think of other methods that we can use to better reduce CDI recurrence.

My research project is a retrospective cohort study evaluating patients at high risk of CDI. We specifically characterize our patients as high-risk if they had at least 2 prior episodes of CDI in the last year prior to the initiation of broad-spectrum antibiotics. And so, we defined 2 prior episodes of CDI as having a positive CDI assay but then also being treated for the C diff episode because we wanted to make sure that we weren't really capturing those patients who may have just been colonized. We're pretty specific in our definition for broad-spectrum antibiotics including lincosamide antibiotics, carbapenems, fluoroquinolones but not necessarily antibiotics that are associated with a lower risk of CDI such as macrolides or tetracyclines. The 2 cohorts included patients who received at least greater than 50% of oral vancomycin for the duration of broad-spectrum antibiotics compared to patients who received no oral vancomycin prophylaxis.

And that greater than 50% of broad-spectrum antibiotics comes from a study where they found a difference in that population, but not in patients who received less than 50% of the duration. So, our primary endpoint was evaluating the incidence of CDI within 12 weeks of initiating broad-spectrum antibiotics and unfortunately, we didn't find a statistically significant difference. We included 108 patients in the study, 88 of which were in the no prophylaxis group compared to 20 in the prophylaxis group.

In the study, 14.8% of patients in the no prophylaxis group an incidence of CDI within 12 weeks and 10% in the oral vancomycin group had an event rate. So there appeared to be a numeric reduction of CDI incidents, but due to the low sample size we were unable to detect a significant difference. In terms of secondary endpoints, we looked at all-cause mortality, all-cause ICU stays, we also looked at VRE colonization to determine whether or not we were causing more VRE colonization which is certainly a concern with the overuse of oral vancomycin in this patient population; so, we don't want to cause harm. Unfortunately, we didn't routinely order VRE surveillance cultures in all of our patients and so didn't necessarily capture an accurate representation of that endpoint.

But I think the most interesting finding that we saw was that there seemed to be a delay in CDI recurrence with the use of oral vancomycin prophylaxis. The vast majority of patients who did not receive oral vancomycin prophylaxis had CDI recurrence with 30 days of broad-spectrum antibiotic initiation — with a few outliers past 30 days. But the patients who received oral vancomycin, only 2 patients had the primary endpoint who were in the world incubation group and those occurrences were out past 30 days and so that is hypothesis-generating in terms of potentially delaying the occurrence of CDI. This actually reduced our hospital-acquired CDI rates and so there were no patients who had hospital-acquired CDI in oral vancomycin prophylaxis group. There were four patients in oral vancomycin prophylaxis group that had hospital-acquired CDI.

I think the biggest takeaway is that oral vancomycin prophylaxis seems to be hypothesis-generating in terms of delaying CDI occurrence. I think that if we're able to reduce hospital-acquired CDI that could potentially help the patient in the more acute phase of their hospitalization if they're able to overcome their more acute illness, and then if they were to have CDI at least it could be less severe.

So, ideally, I think that future research should focus on oral vancomycin prophylaxis for the full duration of broad-spectrum antibiotic therapy and trying to again target that high-risk population who may be at the highest risk of CDI incidence or recurrence, so having multiple recent CDI episodes and initiated on higher risk antibiotics. Future studies should also look at VRE colonization more consistently to see if we're causing harm from that perspective.

Read more about Lew's research here.