Damian McNamara

October 18, 2016

LAS VEGAS — For patients with recurrent Clostridium difficile infections who are treated with fecal microbiota transplantation, clinical response at 4 weeks might be sufficient to assess cure, according to results from a new study.

"If your patients are asymptomatic at 4 weeks, you can feel fairly confident they have achieved a cure; full 8-week follow-up may not be necessary," said Jessica Allegretti, MD, from Brigham and Women's Hospital in Boston.

It is well established that fecal microbiota transplantation is effective for recurrent C difficile infection, and cure rates higher than 80% have been reported, said Dr Allegretti.

The current 8-week post-transplantation assessment was established on the basis of antibiotic response time in this population, because standard antibiotics to fight C difficile infections are bacteriostatic, which means that C difficile test results can be positive for up to 30 days after treatment.

"However, fecal microbiota transplantation has a unique mechanism of action," Dr Allegretti explained. "It establishes a microbial community that directly inhibits C difficile and establishes colonization resistance."

If your patients are asymptomatic at 4 weeks, you can feel fairly confident they have achieved a cure.

Results from the prospective multicenter cohort study were presented here at the American College of Gastroenterology 2016 Annual Scientific Meeting.

Fecal microbiota transplantation delivered by colonoscope led to a cure at 8 weeks in 81% of the 183 study participants, who had experienced at least three C difficile infections. Cure was defined as a negative result on polymerase chain reaction (PCR) or a resolution of symptoms.

On a multivariate analysis, an absence of symptoms at 4 weeks was the biggest predictor of cure (odds ratio, 32.8), with a specificity of 87% and a sensitivity of 91%.

The researchers looked at symptom resolution and PCR results after transplantation.

Table. Outcomes After Fecal Transplantation

Outcome Week 1, % Week 4, %
Negative PCR result 85.2 87.8
Asymptomatic patients    
   All 80.2 77.6
   With Negative PCR result 100 100
   With Positive PCR result 75 54

Given that the addition of PCR to symptom assessment increases accuracy only slightly, and not significantly, the time and expense might not be justified, Dr Allegretti pointed out.

Inflammatory Bowel Disease

However, the situation is different for patients with inflammatory bowel disease and recurrent C difficile infections. "C difficile in these patients can lead to higher mortality, so these are cases you don't want to miss," she explained.

In a subgroup of 44 patients with inflammatory bowel disease, the sensitivity of symptom assessment at 4 weeks was 84.9% and specificity was 81.8%. However, PCR was more accurate at 4 weeks, with a sensitivity of 100% and a specificity of 80%.

"If you have a negative PCR 4 weeks after fecal transplantation, you can feel very confident that a cure has been achieved," Dr Allegretti said.

The small number of patients with inflammatory bowel disease in this study was a potential limitation, she acknowledged, and some stools samples were missing because of poor patient compliance.

The asymptomatic carriage rate after fecal microbiota transplantation is very low.

"We know there are public health implications to asymptomatic carriage," said Dr Allegretti. After being treated with antibiotics, patients with C difficile can have 15% to 30% asymptomatic carriage rates. But again, the mechanism of fecal transplantation differs from that of antibiotics, she explained.

In the study population, the asymptomatic carriage rate at 1 week was 0.8% and at 4 weeks was 1.5%, "so the asymptomatic carriage rate after fecal microbiota transplantation is very low," she reported.

Overall, the findings suggests that an absence of symptoms at 4 weeks is sufficient to indicate a cure in most patients, but if patients are symptomatic, PCR might be warranted, Dr Allegretti said. For patients with symptoms and a positive PCR result at 4 weeks, she suggests retreatment and close follow-up.

"This is a first step. Now we need to validate this process and prospectively look at stopping treatment at 4 weeks to see what happens," she explained in response to a question from the audience. "We also really need to understand the inflammatory bowel disease population. Should we only use PCR and not symptoms? We need prospective studies."

"Pretty Compelling" Results

"These results look pretty compelling to me," said session moderator John Saltzman, MD, from Brigham and Women's Hospital.

"My understanding is that these assessments are more prolonged than they need to be," he told Medscape Medical News. " This study provides data that symptom resolution at 4 weeks can be an early sign of cure, and that PCR testing should be done in inflammatory bowel disease."

Dr Allegretti reports receiving grant and research support from Finch Therapeutics. Dr Saltzman has disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2016 Annual Scientific Meeting: Abstract 7. Presented October 17, 2016.

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