Challenges and opportunities in the management of Clostridium difficile infection

Abstract

Clostridium difficile infection (CDI) is increasing in all regions of the world where sought. There is no gold standard for diagnosis of CDI, with available tests having limitations. Prevention of CDI will be seen with antibiotic stewardship, improved disinfection of hospitals and nursing homes, chemo- and immuno-prophylaxis and next generation probiotics. The important therapeutic agents are oral vancomycin and fidaxomicin with metronidazole being used only in mild cases or when oral therapy cannot be given. Current therapy of CDI for 10 days is associated with high rate of recurrence that may be prevented by prolonging initial therapy. Future treatment strategies will focus on drugs that inhibit C. difficile, reduce toxin activity and inflammation in the gut, and improve colonic flora diversity.

Keywords::

• C. difficile infection
• C. difficile monoclonal antibodies
• C. difficile prevention
• C. difficile recurrence
• C. difficile treatment
• C. difficile vaccines
• Clostridium difficile
• fidaxomicin
• metronidazole
• rifaximin
• vancomycin

Financial & competing interests disclosure

This work was supported in part by grants from Public Health Service (grant DK 56338) which funds the Texas Gulf Coast Digestive Diseases Center. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• One or more biomarkers are needed to help identify patients with Clostridium difficile infection (CDI) versus the more common CDI-negative antibiotic associated diarrhea. Potential tests to aid in the diagnosis of CDI include fecal lactoferrin, fecal calprotectin and fecal IL-8.

• Current diagnostic approaches to identification of CDI have limitations either being too sensitive (e.g., enzyme immunoassay), having false positive results (e.g., PCR) or taking too long to perform (e.g., toxigenic culture and tissue culture cytotoxicity assay).

• New treatment approaches are needed that successfully shorten illness and prevent recurrences. Longer durations of therapy with drugs that spare colonic flora should be studied for effectiveness.

• With the importance of immune response to C. difficile toxins in preventing CDI and CDI recurrence, vaccines and biologics that improve host responsiveness to the toxins should be pursued. Ultimately, a vaccine is likely to be the most cost-effective way to reduce rates of CDI.

• Fecal microbiota transplantation is the most effective treatment for multiple-recurrent CDI. Identifying a mixture of anaerobic gram-positive and gram-negative bacteria may be a successful approach to treatment, which would make intestinal microbial restoration more practical and potentially safer.

• Antibiotic stewardship programs are needed to decrease the use of high-risk antibiotics and to not use antibiotics for doubtful indications such as viral syndromes, bronchitis or sinusitis in otherwise healthy persons, recurrent serous otitis media in children and chemoprophylaxis with unclear indications.

• Improved methods of decontamination of hospital and nursing home environments are needed. Hydrogen peroxide vapor methods and ultraviolet light treatment in addition to hypochlorite treatment should be compared for their value in these settings.

• Further studies of community-acquired CDI and pediatric CDI are needed to define these large vulnerable groups.

• Intervention strategies are needed to identify high-risk patients and to prevent future CDI by drugs or biologics.

Notes