Practice Pearls from the 2018 Clostridium Difficile Treatment Guidelines

Clostridium difficile infection (CDI) is still considered the most common healthcare associated infection in the United States. CDI differs from most other infections as it usually occurs after treatment with antimicrobial therapy. Some of the most commonly associated agents that CDI is associated with include clindamycin, ampicillin, cephalosporins, and fluoroquinolones. It is estimated that CDI costs the United States healthcare system $5 billion every year, and that the incidence for CDI has increased over the past 2 decades.

The Infectious Diseases Society of America (IDSA) in conjunction with the Society for Healthcare Epidemiology of America (SHEA) play a significant role in reducing the burden of this disease with their publication of clinical practice guidelines. Recently, the IDSA and SHEA have made an update to the previously published practice guidelines for CDI in 2010. While many of the recommendations remain the same, there are a few key changes that the update has addressed:

• Inclusion of specific pediatric guidelines
• Discussion on laboratory guided diagnosis in adults
• Removal of metronidazole for 1^st line therapy in adults
• Discussion on fecal transplantation utilization
• Consideration of prophylaxis techniques

Pediatric Guidelines

One of the first aspects that the update addresses is CDI in the pediatric population. The updated guidelines reflect the inclusion of diagnosis, surveillance, and treatment for the pediatric population, which the 2010 guidelines failed to address.

Key Changes in Adult Guidelines

Diagnosis

In addition the added guidelines regarding children, the update has clarified its recommendations for diagnosis of the disease. C. difficile is traditionally diagnosed by a variety of methods which include the past medical history of the patient, symptoms (such as the number of unformed stools in a 24 hour period), and laboratory test results. However, the previous guidelines were unclear due to the types of tests available for C. difficile diagnosis. The updated guidelines attempt to clarify the previously unclear recommendations for laboratory testing in C. difficile patients. Before the emergence of testing methods like the Nucleic Acid Amplification Test (NAAT or molecular testing), institutions utilized Enzyme Immunoassay (EIA or toxin testing) to detect the presence of the organism in a particular sample. However, NAAT has increasingly become the benchmark method for laboratory testing of C. difficile.

The updated guidelines provide a much clearer algorithm for laboratory testing. The initial step of this algorithm is centered upon each institution’s practice. To clarify, if the institution uses only specimens from patients who are not taking laxatives and have at least 3 or more unformed stools in a 24 hour period, then using the NAAT alone is satisfactory. In addition, institutions may recommend using a stool toxin test in a multistep algorithm to satisfy the recommendation. On the other side of the algorithm, the recommendation is an initial testing for C. difficile with glutamate dehydrogenase (GDH), which is then followed by a toxin test. If the immunoassay comes back negative, then the algorithm recommends follow-up with the NAAT. These recommendations are a slight departure from the current preoccupation of NAAT as a standalone method of testing.

Treatment

Step-wise Therapy

One of the most striking changes that can be observed in the updated guidelines is the fact that metronidazole is no longer recommended as a first line treatment, which was previously recommended in the 2010 guidelines. Since then, metronidazole has been widely adopted in clinical practice as an indispensable tool in the fight against the disease. Rather, the new guidelines recommend vancomycin and fidaxomicin as first line treatments for C. difficile. Two important caveats must be added; first, despite the seeming demotion of metronidazole from its original place in therapy, metronidazole can still be considered as first line treatment in situations where accessibility to vancomycin and fidaxomicin is limited. Of importance, metronidazole can be considered so long as the disease classification is mild-to-moderate and not severe. This appears to be a very reasonable concession, considering the fact that metronidazole is considerably cheaper than both vancomycin and fidaxomicin. The second noteworthy caveat involves the consideration of fidaxomicin as a first-line agent, as this drug was only approved by the FDA in 2011 (one year after the publication of the previously published 2010 guidelines).

Fecal Microbiota Transplantation

Another considerable treatment change includes the recommendation on Fecal Microbiota Transplantation (FMT) therapy. This technique, otherwise known as the stool transplant, has now been recommended for the treatment of multiple recurrences of the disease. Previously, FMT was not recommended as an alternative therapy, but the panel has no taken into consideration the superior efficacy of this technique over the conventional antibiotic therapy for multiple recurrences of C. difficile infection.

Prophylaxis

In recent years, probiotic use has become more and more prevalent. While probiotics such as Lactobacillus and Saccharomyces boulardii have been associated with some reduction in C. difficile recurrence, significant results demonstrating efficacy in controlled clinical trials have yet to be seen. Thus, standard utilization of probiotics in the setting of C. difficile is not currently supported.

One challenge clinicians may face is the need to initiate antibiotic therapy soon after completion of C. difficile treatment. In an effort to avoid the recurrence of C. difficile, use of prophylaxis vancomycin 125mg daily or fidaxomicin 200mg daily may be considered. Alternatively, treatment duration may be extended beyond 10-14 days. Further investigation of specific dosing and patient factors to guide prophylaxis dosing and patient selection criteria have yet to be seen in prospective, randomized trials. However, initial studies can provide clinicians with some guidance.

Conclusions

Overall, these updates to the clinical practice guidelines for C. difficile infection in adults and children have clarified many aspects of the previous 2010 guidelines. With these changes, it is the responsibility of healthcare professionals, including pharmacists, to ensure that these updates are taken into consideration when treating patients with C. difficile infection.

References

• Roecker A, Bates B, Martin S. Gastrointestinal Infections and Enterotoxigenic Poisonings. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; .