Experts debate fecal transplants as first-line therapy for CDI

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.