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Lowering C. Diff Infections but Risking Long-Term Resistance

February 09, 2017

When rates of Clostridium difficile (C. diff) began to increase at the Hospital of the University of Pennsylvania, clinical pharmacist Alex Ganetsky, PharmD, and his colleagues at Penn’s Abramson Cancer Center decided to administer oral vancomycin to bone marrow transplant (BMT) patients — who are at particular risk of suffering hospital-acquired infection — before C. diff occurred. The preventative program demands a balancing act between lowering short-term infection and avoiding long-term antibiotic resistance. For Dr. Ganetsky, the risk is worth the reward when trying to protect compromised patients from the devastating consequences of C. diff infection.

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How troubling is the C. diff problem?

It’s becoming an epidemic across the country. Patients who are immunocompromised are at a higher risk of infection, so it’s more of an issue for cancer patients undergoing chemotherapy and BMT patients. Incidence of C. diff among BMT patients is 20 to 30% and 1 out of every 5 patients gets an infection within 2 to 3 weeks of transplant. That’s a staggering number and much higher than rates we saw 20 years ago. The significant increase in infection risk is multifactorial. There’s a heightened incidence of C. diff, so providers are testing for it more often. Antibiotics, which increase resistance, are used much more frequently than in years past. We’re also treating more cancer patients with immunosuppressive therapy, which increases the risk of C. diff. Because of all those factors, incidences of infection will likely continue to increase.

How are pharmacists promoting the appropriate use of antibiotics?

They run antibiotic stewardship programs, develop antibiotic use guidelines, and work as active approvers of antibiotic therapy. They’re tasked with working with infectious disease physicians to develop guidelines for antibiotic use, specifically for antibiotics that are more likely to produce side effects or resistance. There’s a high rate of quinolones resistance at our facility, so the stewardship service must approve their use before they’re administered to patients. We’ve also expanded the stewardship program, so approval is now needed before approximately 30% of antibiotics are used. Medical teams present their case as to why certain antibiotics are needed and infectious disease pharmacists review the patient’s case to see if the requested antibiotic is appropriate. If it’s not appropriate, pharmacists help the medical team figure out an alternative therapy.

Why did you start using vancomycin to prevent infection in bone marrow transplant patients?

We’ve experienced an epidemic of C. diff in general, but it has been the most pronounced in BMT patients. C. diff is problematic because they are the most profoundly immunocompromised patients who are cared for in our hospital, and any infection has the potential to lead to significant morbidity and possible mortality. Infection is clearly not a good outcome, but C. diff has also been identified as an independent risk factor for graft vs. host disease, which is an immune mediated response where the graft attacks healthy recipient tissue and the leading cause of non-relapse-related death in BMT patients. Given the severe consequences of infection in these patients, we thought it was important to figure out a strategy to help mitigate the risk. There are case reports of BMT patients who didn’t develop infection after receiving preventative vancomycin — 2 times daily instead of the FDA-approved 4 times daily to treat C. diff — so we decided to give it a try.

Have your efforts been effective?

We launched a pilot program that involved treating 10 BMT patients with preemptive vancomycin therapy — it’s begun on the day of admission and continued for about a month until the day of discharge — and none of them suffered an infection. We’ve currently treated approximately 95 consecutive patients without a single case of C. diff. It’s been impressive — no one expected the infection rate to decrease to zero. We’re still evaluating whether there’s a secondary benefit of using vancomycin to prevent graft vs. host disease, but it terms of preventing the incidence of C. diff, preemptive use of the antibiotic appears to be working.

Are you worried about vancomycin resistance?

We are. Our hospital’s hematologists, pharmacists, and infectious disease specialists discussed that as a group, and we decided the benefits of using vancomycin to prevent infection would outweigh the risks, because BMT patients basically have no immune system for weeks after transplantation. Given the grave possible sequela of an inappropriately treated infection, we thought it’d be worth piloting a preventative program, while watching closely for the development of resistance. We’re about 14 months into the program and fortunately we haven’t seen any signs of resistance. Does that mean it won’t occur 2 years from now? We’re not sure, but right now there are no signs that resistance is an issue.

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