The Shifting Treatment Paradigm for Initial Clostridioides difficile Infection (CDI)

In the United States, approximately 225,000 cases of Clostridioides difficile infection (CDI) occur in hospitalized patients annually, resulting in approximately 15,000 deaths, and the CDC has classified CDI as an urgent public health threat. Thus, understanding the therapeutic goals for treating initial CDI is critical in reducing the significant morbidity and mortality associated with this infection.

Identifying and Balancing Therapeutic Goals
Therapeutic goals for CDI include correcting the dysbiosis that underlies the pathophysiology of the infection, eradicating the vegetative C difficile organism, and augmenting the host immune response to the infection. Understanding these therapeutic goals allows categorization of treatment modalities into:

1. Microbiota restoration (eg, fecal microbiota transplantation)
2. Microbiologic killing (eg, antibiotics)
3. Immune modulators (vaccines, immunoglobulin, and monoclonal antibodies)

Although these classifications are useful, there is considerable overlap―and at times discordance―among them, particularly when using antibiotics to treat CDI. For example, antibiotics such as metronidazole, fidaxomicin, and vancomycin generally have good clinical activity against C difficile, and they further disrupt the damaged microbiome that led to the development of CDI in the first place. In fact, most treatment guidelines for CDI now generally discourage the use of metronidazole for initial treatment of CDI due to its lower clinical response rate compared with that of vancomycin. 

High Rate of Recurrence
However, often overlooked is an unacceptably high recurrence rate of 20% to 25% in patients who receive metronidazole or vancomycin for their first occurrence of CDI. Of importance, fidaxomicin is associated with lower recurrence rates than are metronidazole or vancomycin, presumably due to its narrow spectrum and lower disruption in the microbiota. Adding bezlotoxumab also is an option in patients at higher risk of recurrence. That said, the possibility of recurrence exists with any treatment, which reminds us that recurrence is still a clinical challenge.

Where Do We Go From Here?
To me, the key question now is how do we more effectively incorporate appropriate therapies into our treatment algorithm for initial CDI? First and foremost, we must recognize that the therapeutic goal of treating CDI is to sustain clinical cure—achieving clinical response without recurrence. Any initial clinical improvement that is not sustainable should be considered a treatment failure.

Once that is recognized, infectious diseases experts and antimicrobial stewardship teams can use their skill and ingenuity to ensure a high rate of sustained clinical cure including the use of guideline-recommended therapies.

Other strategies that may provide benefits include improving access to care by ensuring that appropriate treatment is available in the hospital and community pharmacy settings, discharge planning processes that include knowledge of insurance requirements and copayment reductions, and patient discharge instructions to prevent recurrent CDI. There are considerable healthcare-related benefits (eg, decreased hospital readmissions and healthcare costs) from decreasing CDI recurrences and improving patient-related outcomes such as quality of life. Pilot projects at hospitals newly starting anti-CDI recurrence strategies also can document these downstream economic benefits.

Once these implementation strategies are adopted by the medical community, I believe we can begin a new era to drive sustained clinical response rates even higher to benefit all patients with CDI.

Your Thoughts?
Which strategies are being implemented to achieve a sustained clinical cure for CDI in your community? Join the conversation by posting in the discussion section.