FMT Decreases Antimicrobial Resistance in Study of Children with C diff


A new study using shotgun metagenomic sequencing found that FMT yielded a sustained decrease in antimicrobial resistance genes and potential pathogens in children with recurrent C diff.

Fecal microbiota transplantation (FMT) in children with Clostridioides difficile infection (C diff) reduced antimicrobial resistance genes and potential pathogens, a new study found.

The study, published in Open Forum Infectious Diseases, included 9 patients younger than 21 years with recurrent C diff identified at Inova Fairfax Hospital and the Johns Hopkins Medical Institute. Stool samples were collected and analyzed before and after FMT for up to 24 weeks. Healthy adult donors were screened for potential pathogens.

C diff symptoms resolved within 3 days of FMT for all patients, with no recurrences reported during the follow-up time. While antimicrobial resistance (AMR) genes existed in all samples, they dropped substantially, and those decreases were sustained throughout the study. Multidrug resistance genes also fell.

“We were a bit surprised at the persistence of the FMT intervention and the significant sustained reduction in antimicrobial resistance and potential pathogen burden,” corresponding author Suchitra Hourigan, MD, and senior authors Maria Oliva-Hemker, MD, and Keith Crandall, PhD, said in a written statement to Contagion®. “Our data are fairly unique in terms of looking at multiple timepoints beyond the initial FMT treatment and our patients showed they sustained their initial increase in diversity over time after the FMT intervention.”

Hourigan is a pediatric gastroenterologist affiliated with Inova Fairfax Hospital. Oliva-Hemker is the Stermer Family professor of pediatric inflammatory bowel disease and a professor of pediatrics at Johns Hopkins University School of Medicine. Crandall is the founding director of the Computational Biology Institute at George Washington University.

Investigators used shotgun metagenomic sequencing and advanced bioinformatic tools to examine fecal samples of donors and recipients. After FMT, fecal samples of the patients more closely resembled those of the donors than of their pre-FMT samples, with increases in alpha diversity continuing throughout the 24 weeks of observation. High levels of proteobacteria, particularly Gammaproteobacteria, were identified in recipients before FMT. Healthy samples included Clostridia and Bacteroidia.

Donor stools were provided by relatives or commercial donor banks.

“We would very much like to continue this study with larger numbers and test hypotheses focused squarely on the donor material as well (commercial versus related, etc.),” the investigators told Contagion®.

FMT has recently been the subject of controversy, with the US Food and Drug Administration (FDA) warning health care providers and patients after bacterial infections associated with the treatment were reported in 2 patients, including 1 death. FMT is not approved by the FDA.

These incidents raised questions about the future of FMT and how donor materials should be regulated, selected and screened, underscoring the need for more research into the safety and efficacy of microbiome therapies.

“As shown in several papers, FMT for recurrent C. diff infection works, and we also showed in general there is a reduction in antibiotic resistance and pathogens with FMT,” the study authors said. “However, you must be careful with your donor material, including prescreening before application for pathogens and antibiotic resistance. Metagenomics provides a potential efficient way to get this done.”

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