PPIs, histamine blockers may be OK during therapy for C difficile

Last Updated: 2015-03-11

By Larry Hand

NEW YORK (Reuters Health) - Individuals who develop Clostridium difficile-associated diarrhea (CDAD) while taking proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) do not have to stop their acid-suppressing drugs to avoid diarrhea recurrence, according to a new study.

"Our results show that development of CDAD does not require discontinuation of PPI or H2RA treatment in patients who have an indication for continuing such therapy," such as gastroesophageal reflux disease, Dr. Karl Weiss, of the Department of Infectious Diseases and Microbiology at the University of Montreal in Canada, told Reuters Health by email.

"Some studies have reported that PPI/H2RA use increased the risk of (diarrhea) recurrence, but the studies had small sample sizes and were not carefully controlled," he said.

Also, the U.S. Food and Drug Administration issued a safety communication in February 2012 recommending that patients "immediately contact their healthcare professional and seek care if they take PPIs and develop diarrhea that does not improve."

Dr. Weiss and colleagues conducted a post hoc analysis of two phase III trials involving 701 inpatients with CDAD randomized to receive either fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times a day) for 10 days.

Overall, 482 (69%) used PPIs or H2RAs at some time during the treatment, the researchers wrote March 2 online in BMJ Open Gastroenterology, including 380 (54%) who used PPIs, 55 (8%) who used H2LRAs, and 12 (2%) who used both.

During follow-up, 389 (55%) used PPIs, 54 (8%) used H2RAs, and 18 (3%) used both.

On multivariate analysis, PPI and/or H2RA use had no effect on CDAD recurrence rates or time to resolution of diarrhea.

Treatment with fidaxomicin, however, was a significant predictor, reducing the odds of diarrhea recurrence in half (odds ratio 0.498, p=0.003) compared with vancomycin.

Leukocytosis, elevated creatinine, and hypoalbuminemia were also associated with poor clinical responses.

"Although it is not our intention to encourage the use of PPIs or H2RAs, we have found that such concurrent treatment did not adversely affect CDAD treatment outcomes among inpatients with CDAD," the researchers write. "In conclusion, these data support a position that acid suppression therapy, when indicated, can be maintained during treatment of CDAD."

So what research is needed now? "There are two issues here in terms of future studies," Dr. Weiss said.

First, he would like to see a long-term study of the risk of CDAD during chronic PPI treatment - although this would be "costly and time-consuming," he admits.

And second, he said, "The major issue with C difficile is recurrence within 90 days of the initial episode. Fidaxomicin represents a breakthrough over the previous available options, but can we go for shorter treatment, combination therapy . . . notably in the elderly?"

The study was funded by Cubist Pharmaceuticals, which markets fidaxomicin as Dificid and Dificlir. Cubist employed one author and has financial relationships with two others. Another author was employed by bioMerieux.

SOURCE: http://bmj.co/1BwsLa4

BMJ Open Gastroenterol 2015.