C. difficile diaries: New frontiers in treatment and prevention

10/23/2024

Clostridioides difficile infection is a significant contributor to morbidity across the general population, posing an especially high risk of complications and recurrences. This is particularly concerning in vulnerable groups, such as older adults and those with underlying health conditions.

Not long ago, fidaxomicin gained recognition as a first-line treatment for CDI, offering improved outcomes and reducing recurrences, especially for immunocompromised patients. (1) As the incidence of CDI continues to grow, especially among high-risk populations, fidaxomicin’s targeted therapy may be pivotal in enhancing patient outcomes and mitigating the broader health care burden associated with this difficult-to-treat infection. (2)

While fidaxomicin is increasingly recognized as a preferred treatment for CDI, its high cost remains a significant barrier to its widespread adoption within health care systems. Due to financial constraints, many institutions may need to limit its use in patients meeting certain criteria rather than making it a standard option for all CDI patients. In the outpatient setting, insurance companies frequently require patients to first fail on treatment with oral vancomycin before approving fidaxomicin.

Need for comprehensive strategies, concerns about resistance

The challenge of balancing cost and care underscores the pressing need for comprehensive strategies to address this emerging issue at its core. (3) With the Centers for Disease Control and Prevention indicating that 30% of CDI cases will experience a first recurrence — and the risk of further recurrences rising with each subsequent episode — it’s not fair to continue to subject patients to oral vancomycin, hoping that luck will be on their side. (4)

In the current era of antimicrobial resistance, the potential for oral vancomycin resistance in the treatment of CDI presents a serious threat to global health. While vancomycin has long been a reliable treatment for CDI, emerging reports of reduced susceptibility in some C. difficile strains are deeply concerning. (5) Research is urgently needed to further elucidate the mechanisms behind vancomycin resistance and to understand its clinical implications fully.

However, a significant challenge in identifying and addressing this issue lies in the fact that most clinical laboratories do not routinely perform C. difficile susceptibility testing. (6) Furthermore, if CDI recurrences are seen as a sign of vancomycin therapy failure, we may be missing a crucial warning of rising oral vancomycin resistance. By continuing to rely on vancomycin without recognizing these emerging patterns, we risk providing suboptimal therapy to our patients. (5-7)

Recurrence prevention, new drugs

Given the significant burden that CDI places on health care, there’s also growing emphasis on preventing recurrence. There is no replacement for handwashing and strict adherence to proper isolation and hygiene measures in preventing the spread of infection.

Beyond these measures, one effective approach that has gained recognition is fecal microbiota transplantation, which can disrupt the cycle of recurrent CDI. However, the procedure can be challenging for patients, as it often requires a colonoscopy, and its availability is still somewhat limited. (8)

The approval of REBYOTA in 2022 and oral VOWST in 2023 could be game changers in the fight against recurrent CDI. These products, newly approved by the Food and Drug Administration, offer promising alternatives to traditional FMT, with both showing significant benefits in preventing infection recurrence. (9,10) Bezlotoxumab, a monoclonal antibody targeting C. difficile toxin B, is another medication on the market that holds potential, particularly for use in immunocompromised patients. (11)

Recently, we managed a patient with chronic immunoglobulin G deficiency who was experiencing recurrent CDI. To break the cycle of recurrence, all three novel modalities mentioned above were offered in conjunction with fidaxomicin. FMT was deferred by the patient due to personal preferences.

This encounter raised important questions about whether clinical evidence supports choosing one specific therapy over the others among the three options. Despite these treatments being available for some time, there remains a notable lack of head-to-head comparative data to guide optimal decision-making.

Looking ahead

The CLOVER trial tested a new vaccine, PF-06425090, to see if it could help fight CDIs. While the vaccine was safe, it didn’t hit its main goal but did show some promise by reducing the duration of symptoms and the need for antibiotics. Even though this vaccine hasn’t provided a breakthrough, there’s still hope that an effective C. difficile vaccine will be available one day. (12)

In the meantime, making fidaxomicin more affordable and widely accessible, along with utilizing novel treatment modalities (REBYOTA, VOWST or bezlotoxumab), could significantly strengthen our efforts to combat this old foe.

References

Science Speaks

C. difficile diaries: New frontiers in treatment and prevention

Syed Feeroz, BS

Mahreen Anwar, BS

Shamsuddin Anwar, MD