Tips for treating C. difficile in IBD

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight