Fecal Transplantation, Molecular Testing Among New Recommendations in C. diff Guidelines

New diagnostic methods and treatments – including fecal transplantation – will help improve the care of patients with Clostridium difficile (C. diff.), a deadly bacterial infection that can occur after antibiotic use, according to updated guidelines released by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and published in the journal Clinical Infectious Diseases. 

C. diff. sickens nearly 500,000 Americans annually, a rate that plateaued in 2010 after reaching historic highs, but has yet to decline in the United States as it has in England and parts of Europe. The most common bug acquired in the hospital, C. diff. kills 15,000 to 30,000 people every year and costs more than $4.8 billion a year in hospitalizations alone.

C. diff. has become a significant problem due to the excessive use of antibiotics, which disturb the balance of bacteria in the gastrointestinal system, wiping out good bacteria and allowing the C. diff. bacteria to flourish and cause cramps and diarrhea. Some patients suffer from repeated recurrence despite standard antibiotic treatment.

Diagnosis and treatment of C. diff. has evolved significantly since the last guidelines were published in 2010.

“We can better control this epidemic by learning how to use new treatments and diagnostics,” said L. Clifford McDonald, MD, co-chair of the guidelines panel and associate director for science in the Division of Healthcare Quality Promotion for the Centers for Disease Control and Prevention (CDC). “The role of the infectious disease specialist is critical, not only in providing expert diagnosis and treatment of C. diff. infections, but also in helping set institutional policies that will lead to their prevention – including reducing the inappropriate use of antibiotics through good stewardship.”

C. diff. is diagnosed based on a patient’s medical history, signs and symptoms, combined with test results. The optimal method for laboratory diagnosis of C. diff. is the subject of debate and depends on how carefully patients are selected for testing. The guidelines recommend only testing patients with new onset and unexplained diarrhea (three or more unformed stools in 24 hours). While immunoassays were the most common diagnostics employed previously, molecular testing – which has its pros and cons – is now used by more than 70 percent of hospital labs. Molecular tests can help rule out C. diff. infection, as well as reduce transmission by detecting C. diff. colonization in patients with diarrhea from other causes. But because they are very sensitive and can lead to over diagnosis, when there are no pre-agreed institutional criteria that limit testing to patients with significant unexplained diarrhea of three or more unformed stools in 24 hours, the guidelines recommend that a C. diff. common antigen test and a stool toxin test (such as an immunoassay) be used as part of a two- or three-step test process.

Further, not everyone diagnosed with C. diff. requires treatment, notes McDonald. “We often find people get better on their own if they stop taking the offending antibiotic,” he said.

The guidelines include new recommendations for treatment when warranted, including:
- Vancomycin or fidaxomicin – Antibiotics vancomycin or fidaxomicin should be used for initial treatment of even mild C. diff., rather than metronidazole, which the previous guidelines recommended as first-line therapy. Research shows the cure rates are higher for vancomycin and fidaxomicin than for metronidazole.

-  Fecal microbiota transplantation (FMT) – The guidelines recommend FMT for treatment of people with two or more recurrences of C. diff. and for whom traditional antibiotic treatment has not worked. FMT is a new treatment since the last guidelines were published but is not approved by the Food and Drug Administration (FDA). However, FDA has issued Guidance for Industry regarding the use of FMT to treat C. diff. infection not responsive to standard therapies (https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm361393.pdf). FMT involves transferring fecal bacteria from a healthy person’s stool to the gut of a person with recurrent C. diff., to replenish the good bacteria and control the disease-causing bacteria.

The guidelines include the same suggestions for preventing the spread of C. diff. as the 2010 guidelines – including isolating infected patients and ensuring healthcare workers and visitors use gloves and gowns – but also call for increased attention to antibiotic stewardship to reduce the unwarranted use of the drugs. While nearly all antibiotics predispose people to C. diff., some are of particular concern, including the fluoroquinolones, cephalosporins and clindamycin.

The guidelines make no recommendation for the use of probiotics. “We tell patients that for the most part they won’t hurt, but at this point we can’t make a recommendation for which ones to use and specifically how to use them,” said McDonald.
The new guidelines also include recommendations for epidemiologic surveillance, diagnosis, and treatment of C. diff. in children, which the 2010 guidelines did not address.

The IDSA/SHEA guidelines panel includes experts who specialize in epidemiology, diagnosis, infection control and clinical management of adult and pediatric patients. In addition to Dr. McDonald, the guidelines panel includes co-chairs Dale N. Gerding, MD, and Stuart Johnson, MD, and members Johan S. Bakken, MD, PhD, Karen C. Carroll, MD, Susan E. Coffin, MD, Erik R. Dubberke, MD, MSPH, Kevin W. Garey, PharmD, MS, Carolyn V. Gould, MD, Ciaran Kelly, MD, Vivian Loo, MD, Julia Shaklee Sammons, MD, MSCE, Thomas J. Sandora, MD, MPH, and Mark H. Wilcox, MD.
IDSA has published more than 50 treatment guidelines on various conditions and infections, ranging from HIV/AIDS to skin and soft tissue infections. As with other IDSA guidelines, the Clostridium difficile guidelines will be available in a smartphone format and a pocket-sized quick-reference edition. The full guidelines are available free on the IDSA website at www.idsociety.org.

Source: Infectious Diseases Society of America (IDSA)