The effectiveness of faecal microbiota transplant (FMT) in managing relapsed or recurrent C. difficile infections suggests the therapy should be available earlier in the disease process, Australian clinicians say.

A case series of 25 FMT procedures in 19 patients at a single centre in Melbourne found each patient received a median of five courses of oral vancomycin and two courses of metronidazole prior to FMT.

Patients had about three C. diff episodes prior to FMT and the time from first diagnosis of C. diff to first FMT was 4.4 months. After FMT, the median time to resolution was two days.

Five patients required more than one FMT procedure for reasons such as primary failure of the procedure, anticipated inadequate response, or recurrent C diff infection triggered by subsequent antibiotic use.

“This real-world Australian tertiary centre cohort had response rates consistent with the reported literature of approximately 80% following the first FMT and approaching 100% after the third FMT,” the study authors said.

They also found that FMT was well tolerated with only one serious possible adverse event and three deaths which were unrelated to FMT.

The adverse event was an antinuclear antibody (ANA)-positive constitutional illness in a patient with no previously known autoimmune conditions. The patient developed fatigue, arthralgias and constipation one month following FMT, was diagnosed of fibromyalgia by a rheumatologist 13 months later, and then diagnosed with Hashimoto thyroiditis by an endocrinologist three months later.

She has additionally been diagnosed with chronic fatigue syndrome and rosacea by her general practitioner. The patient’s donor was her 30-year-old son who had no medical history and an entirely normal donor work-up.

“Therefore, along with requirements for an FMT registry in Australia as part of the regulatory framework, proscriptive medium- to long-term follow up of recipients of FMT is recommended,” the authors wrote in the Internal Medicine Journal.

The investigators suggested that given the efficacy of FMT, earlier administration should be considered to achieve cost-effectiveness and reduce morbidity.

Senior investigator Associate Professor Mayur Garg, director of gastroenterology at Northern Health, told the limbic the evidence would certainly favour referral for FMT on the second recurrence of C. difficile or even earlier in moderate-severe disease.

“And I think we are moving towards that. I think it’s just increasing familiarity that is going to lead to that.”

Associate Professor Garg said some patients weren’t known to gastroenterologists early.

“They are usually treated under general medicine or infectious diseases teams who aren’t usually the ones who perform FMT. They may feel that there has been a partial response and persist with antibiotic therapy, and so it is important to establish good relationships with our colleagues in these fields,” he said.

“And also many of these patients are quite comorbid so there may be a reluctance to refer them for what may be viewed as an invasive procedure by non-gastroenterologists.”

Associate Professor Garg said the possible adverse event highlighted the need for some caution.

“Having good data collection and a governance framework as well as some kind of registry when a health service takes on FMT, is particularly important.”

He said FMT was still evolving in Australia and there was something of a lag in terms of standardising for FMT.

However the advent of commercial stool banks was very welcome to expedite access as well as avoid ethical and other issues from using patient-directed donors.

“There are still relatively few health care services that are able to offer FMT and as a consequence people are just getting familiar with it.”

Associate Professor Garg said FMT was effective in more than 90% of patients for the treatment of C. difficile.

“There is absolutely no doubt that it is highly effective procedure for patients with this condition and it is one of the more satisfying procedures that we perform – when someone has been quite sick for months, and then gets transformed virtually overnight as a result.”

“It’s about the next stage in terms of how we regulate and govern the process that is now important.”