Rifaximin Shows Promise in Patients With C Diff Infection That Does Not Respond to Metronidazole


Metronidazole is commonly used to treat Clostridium difficile infection, however, it has higher rates of therapy failure.

A new study indicates that individuals with recurrent Clostridium difficile infection (CDI) who failed to respond to treatment with metronidazole could benefit from rifaximin.

The study, published in Cureus, found that rifaximin produces optimal results in patients with diarrhea that has persisted for fewer than 3 weeks. The study investigators noted that the incidence and severity of CDI has been on the rise worldwide, which has mainly been driven by the growth of drug-resistant CDI strains.

Metronidazole is among the drugs that are typically used to treat CDI; however, the study authors noted it has higher rates of therapy failure, potentially because of greater bacterial resistance. Even when metronidazole is effective, up to 1 in 4 patients treated with the oral formulation or with oral vancomycin experience recurrence.

The study noted that the rate of recurrence is higher with subsequent rounds of treatment. The investigators sought to determine how antibiotic rifaximin may affect patients who no longer benefit from treatment with metronidazole.

“This drug has been used to counter the recurrence rate of CDI and the results have been enlightening,” they wrote in the study. “Rifaximin has also played a role in alleviating the risk of hepatic encephalopathy in patients with decompensated liver disease and even for Crohn's disease.”

However, scientific literature related to rifaximin for recurrent CDI is limited, according to the authors. For the current study, the investigators recruited 200 patients who developed diarrhea after a 7-day course of antibiotics, had a stool test that was positive for CDI, and were unresponsive to metronidazole.

The patients had a mean age of 45.41 years with approximately similar numbers of males and females divided into 2 cohorts. Patients in the first cohort were administered rifaximin at a dose of 200 mg 3 times per day for 10 days, whereas the other cohort served as a control group and were not administered a new treatment. The study’s primary endpoints were resolution of diarrhea following 2 weeks of treatment and a negative stool test.

The study showed that rifaximin was effective in approximately two-thirds (65%) of cases. The data showed that age and gender did not affect whether therapy was successful, but the duration of diarrhea did. Patients with diarrhea that lasted under 3 weeks had a success rate of 70.5%, whereas patients with fewer than 3 weeks of diarrhea had a treatment success rate of 55.3%.

However, the investigators noted that the sample size was too small to determine whether other factors may be associated with rifaximin’s treatment success. Despite rifaximin showing promising results, the study authors expressed concern regarding the potential development of resistance to the drug.

“This is attributed to genetic mutations in the beta subunit of ribonucleic acid (RNA) polymerase,” they wrote. “However, extensive research is required to explore the factors associated with rifaximin resistance to develop strategies to mitigate the process.”

They concluded that in the future, larger studies are needed to validate the findings in this patient population.


Waqas M, Mohib K, Saleem A, et al. (April 14, 2022) Rifaximin Therapy for Patients With Metronidazole-Unresponsive Clostridium difficile Infection. Cureus 14(4): e24140. doi:10.7759/cureus.24140

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