Updated C difficile Infection Clinical Guidance From IDSA/SHEA

In the commentary below, Larry K. Kociolek, MD, MSCI, associate medical director of infection prevention and control at the Ann & Robert H. Lurie Children’s Hospital of Chicago, summarizes the revised Clostridium difficile guidelines released by IDSA and SHEA.

On February 15th, an updated clinical practice guideline for Clostridium difficile infections (CDI) was published online in the journal Clinical Infectious Diseases.¹ The comprehensive clinical practice guideline addressing the epidemiology, diagnosis, treatment, and prevention of CDI was written by a multinational expert panel of physicians and was endorsed by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline, which is an update from the previous 2010 IDSA/SHEA CDI guideline, will serve as a very important resource to the medical, infection prevention, and public health communities. It also presents several unresolved aspects of CDI diagnosis, treatment, and prevention that highlight important potential research opportunities for the academic community. Globally, CDI remains an urgent public health problem. In the United States, CDI is the most common healthcare-associated pathogen,² with a half a million cases and more than 29,000 deaths attributable to C difficile each year.³

Recommendations for treatment of CDI in adults have been revised significantly. A strong recommendation from the panel, citing high-quality evidence, now favors a 10-day course of vancomycin or fidaxomicin rather than metronidazole for first-line therapy of mild/moderate CDI in adults. This new recommendation was based on several clinical trials demonstrating greater cure rate and less frequent recurrence following vancomycin compared with metronidazole. The increased cost of vancomycin can be somewhat mitigated by compounding the intravenous formulation for oral administration. Fidaxomicin, also a newly recommended first-line therapy for mild/moderate CDI in adults, may reduce the risk for recurrent CDI because of its narrow spectrum compared with vancomycin.

Recommended treatment strategies for recurrent CDI, a complication that occurs in approximately 25% of patients, have also been revised. However, because of limited comparative effectiveness data for several potential treatment options for recurrent CDI, the strength of these recommendations is less strong than those for incident CDI. Following initial CDI treated with a 10-day course of vancomycin, either a several-week tapered and pulsed course of vancomycin or a 10-day course of fidaxomicin is recommended. For most patients, probiotics can be considered because of favorable cost and safety, although definitive efficacy data for probiotics to prevent recurrent CDI are still lacking. For multiply recurrent CDI (ie, at least 3 CDIs), correction of the patient’s underlying intestinal microbiota perturbation with fecal microbiota transplantation (FMT) should be strongly considered based on several recent clinical trials that have documented efficacy and favorable short-term safety of FMT. Appropriate donor selection and screening should continue to be a priority for centers performing FMT.

The updated guideline also provides recommendations for treatment of children with CDI, although a lack of robust comparative effectiveness data for CDI in children precludes strong recommendations from the panel. As opposed to adults, metronidazole can still be considered for treatment of an initial or first recurrence of mild/moderate CDI in children, but vancomycin is preferred for multiply recurrent and/or severe CDI. Fidaxomicin is currently undergoing phase 3 investigation in children. FMT can be considered in children with multiply recurrent CDI, although published safety and efficacy data in pediatric populations are relatively limited. 

The diagnosis of CDI, namely reliably differentiating infection and colonization, remains an important clinical challenge. Molecular tests (eg, nucleic acid amplification tests [NAATs], such as polymerase chain reaction), which do not differentiate colonization and infection, are now the most commonly used test for CDI among US hospitals. NAATs have the potential to misdiagnose patients with colonization as having CDI, particularly when used in patients with low likelihood of CDI. Thus, this guideline strongly reinforces the importance of practicing good diagnostic stewardship and limiting C difficile testing to patients with new-onset, unexplained, and clinically significant (ie, at least 3 unformed stools in a 24-hour period) diarrhea.

Furthermore, formed stools should not be tested for C difficile, nor should patients be retested within 7 days of a previous negative C difficile test. In pediatric populations, because of the unclear role of C difficile as a cause of diarrhea in infants, children less than 12 months of age should not be tested, and testing should be used with caution in children 12 to 24 months of age and only after consideration for other infectious and non-infectious diarrheal causes.

Because of limited data regarding the optimal C difficile testing strategy, the guideline provides weak recommendations for potential testing strategies to be used by healthcare centers. The recommended strategies vary depending on each institution’s ability to enforce good diagnostic stewardship practices. If testing can be reliably avoided in patients who are unlikely to have CDI, NAAT alone or one of several multistep strategies (ie, a combined assay for glutamate dehydrogenase and toxin [with or without NAAT for glutamate dehydrogenase-positive but toxin-negative stools], or NAAT followed by toxin testing) are among the several recommended testing strategies. However, if diagnostic stewardship is not an achievable goal, use of NAAT alone is likely to lead to frequent misdiagnosis of CDI among patients with C difficile colonization. In these cases, NAAT alone should be avoided and a multistep algorithm that incorporates toxin testing is recommended.

The expert panel reviewed the available data regarding CDI diagnosis, treatment, and prevention exhaustively. However, because of relatively low-quality evidence of various aspects of CDI, the expert panel identified several ongoing research gaps. Although we have made great strides in our understanding of CDI over the last decade, we still have a lot to learn about this important infection. In the meantime, this document provides healthcare providers with a wealth of knowledge to best treat and prevent CDI in their patient populations.

Larry K. Kociolek, MD, MSCI, is the associate medical director of infection prevention and control at the Ann & Robert H. Lurie Children’s Hospital of Chicago and assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

References

1. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) [published online February 15, 2018]. Clin Infect Dis. doi: 10.1093/cid/cix1085
2. Magill SS1, Edwards JR, Bamberg W, et al; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198-1208.
3. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825-834.