Secondary Prophylaxis Did Not Significantly Reduce CDI Rates


While vancomycin SP reduced the recurrent rate 7.5%, compared to metronidazole, it was not statistically significance.

Clostridium difficile infection, C. diff, secondary prophylaxis, oral vancomycin, oral metronidazole, lV metronidazole

Secondary prophylaxis (SP) combined with oral vancomycin or oral/IV metronidazole when initiated with antibiotics for Clostridium difficile infection (C. diff) treatment, did not significantly reduce recurrence rates, according to a study conducted by University of Rochester/Highland Hospital.

The study’s purpose was to assess the efficacy of prophylaxis within a year of previous C. diff infection and determine the time frame in which prophylaxis offers protection against recurrent infections.

“Although the guidelines do suggest that metronidazole is still valid first-line treatment for mild disease now — for patients with just diarrhea and no systemic signs,” Daniel Freedberg, MD, MS, Columbia University, told MD Magazine. “But, really, there are 2 reasons why you would probably use metronidazole instead of vancomycin. One is cost. So, a metronidazole 10-day course costs about $10 instead of hundreds of dollars, which is the cost for vancomycin.”

Researchers looked at subsequent courses of antibiotics and C. diff in patients with initial positive C. diff testing from 2013—2016. A positive C. diff test within 90 days of antibiotics was considered a recurrence. The use of subsequent antibiotics courses in Highland Hospital, Strong Memorial Hospital and UR/Medicine outpatient clinics were noted, along with other factors associated with C. diff relapse: age, gender, date of birth, date of positive test (s), antibiotic exposure, oral vancomycin dose, antacid and probiotic usage, immunosuppressive conditions, fecal transplant, date of death and residence in a skilled nursing facility.

There were 597 antibiotic episodes in 230 patients, with 130 episodes (21.8%) of patients receiving SP, however the difference of recurrence rates with and without antibiotics were not statistically significant (9.2% versus 10.7%).

When used with metronidazole there was no difference in recurrence rates, however, vancomycin SP reduced the rate to 7.5%. Probiotics were also associated with a higher rate of recurrence (16.5% versus 8.9%).

The rate of relapse fell significantly with increasing time since the index case of C. diff.

The retrospective study does not support the routine use of metronidazole in subsequent antibiotic courses following C. diff infections. The limitations of the study do not eliminate the possibility of utilizing vancomycin as prophylaxis, but it requires further studies.

“Metronidazole is a difficult drug to take. It tastes terrible. It causes upset stomach. You can’t drink alcohol with it, so that’s an important point,” Lawrence Brandt, MD, Albert Einstein College of Medicine, told MD Magazine. “I think that the recurrence rates, which are a very real problem with Clostridium difficile, are greater with metronidazole than they are with vancomycin.”

Overall, secondary prophylaxis did not significantly reduce recurrence rates, as there was no real statistical significance with either metronidazole or vancomycin.

The study conducted by the University of Rochester/Highland Hospital fared differently to a similar study conducted in December 2016 measuring whether oral vancomycin as secondary prophylaxis reduced the risk of recurrence in patients recently diagnosed with C. diff undergoing subsequent antibiotic exposure.

Participants were diagnosed with C. diff between 2003—2011 and received antibiotics not targeted against C. diff within 90 days after diagnosis. Recurrence occurred after exposure to antibiotics in 181 (32.9%) of patients, while older patients endured a greater chance.

Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose C. diff antibiotic exposure was a recurrence, but not in those whose C. diff antibiotic exposure was an initial episode. In this instance, oral vancomycin prophylaxis appeared as an effective strategy for decreasing the risk of further C. diff recurrence in patients with a history of recurrent C. diff re-exposed to antibiotics.

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