Rifaximin Effective in Treating Non-Responsive C Difficile Infections

A large proportions of patients with C difficile infections do not respond to metronidazole.

New research suggests rifaximin could be an effective treatment option for patients with clostridium difficile infections (CDI) who do not respond to metronidazole.

A team, led by Muhammad Wagas, evaluated the efficacy of rifaximin in metronidazole non-responsive patients with C difficile infections.

Rifaximin is an antibiotic that has only shown marginal resistance against C difficile bacteria. However, metronidazole is also ineffective in many cases because of resistant strains.

“The exact cause of failure is unknown but the possibilities include the emerging resistance of bacteria, increasing disease severity, and poor immune-mediated response in patients,” the authors wrote.

The Study

In the cross-sectional study, the investigators examined 200 cases of C difficile in patients at the Lahore General Hospital in Pakistan. The mean age of the patient population in the treatment group was 45.41 ± 8.54 years. The majority were aged between 35-50 years.

Included in the study were patients who developed diarrhea following antibiotic treatment for 7 days and had stool test positive for C difficile as detected by the enzyme immunoassay and were unresponsive to metronidazole.

The patients were either treated with 200 mg tablets of rifaximin 3 times daily for 10 days or not given new treatments.

Efficacy

The investigators defined efficacy of the treatment as the resolution of diarrhea after 2 weeks of therapy and a negative stool test.

Most patients had watery diarrhea, abdominal cramping, and the loss of appetite on presentation. The investigators found rifaximin was significantly effective in the resolution of symptoms of CDI in patients who were previously unresponsive to metronidazole (P <0.00001).

Patients who had diarrhea for more than 3 weeks were also significantly associated with failure of therapy (P = 0.03).

“We concluded that rifaximin therapy is effective for patients of CDI non-responsive to metronidazole in more than 65% of the cases,” the authors wrote. “Even though several new developments are made to address the concerned subject, such as microbiota transplantation, antibiotics, and immunotherapy, rifaximin can be considered for patients with metronidazole non-responsive CDI.”

RBX2660

There are several new treatments for C difficile in the form of live microbiome therapeutics, which are based on the success of fecal microbiota therapeutics.

One such treatment is RBX2660, which is being tested for patients with recurrent C difficile infections.

RBX2660 is a standardized, stabilized, investigational microbiota-based live therapeutic. Currently, standard-of-care for patients with recurrent C difficile infections is antibiotics, with consideration of fecal microbiota transplantation following multiple recurrences.

However, it is unlikely the US Food and Drug Administration (FDA) approves FMT as a viable treatment, paving the way for live microbiome therapeutics like RBX2660 to fill the gap.

Overall, the treatment success rate was 78.9% (n = 112) in the RBX2660 group, compared to 30.7% (n = 23) for the historical control cohort (P <0.0001).

In the post-hoc analysis, 91% (n = 88) of evaluable RNX2660 responders remained CDI incidence-free for the 24 months following treatment.

The study, “Rifaximin Therapy for Patients With Metronidazole-Unresponsive Clostridium difficile Infection,” was published online in Cureus.