By Misty Lamprecht, MS, APRN-CNS, AOCN®, BMTCN®
Infection with Clostridioides difficile (commonly referred to as C. diff; formerly Clostridium difficile) is an extreme example of a type of gut microbiome dysbiosis that can occur in patients with cancer. C. diff is a gram-positive, anaerobic, spore-forming, toxigenic bacterium, and infection is acquired via fecal-oral transmission and can cause symptoms ranging from uncomplicated diarrhea to pseudomembranous colitis and toxic megacolon. Because of many common risk factors (e.g., use of antibiotic therapy, advanced age, exposure to healthcare environments, immunosuppression), the hematology and oncology population is at high risk for C. diff colonization or infection.
Multiple studies conducted from 2014–2018, including one in which I was co-investigator, found that 9.3%–14% of patients with cancer admitted to the hospital were colonized with toxigenic C. diff (see sidebar). Our study looked specifically at the efficacy of a polymerase chain reaction (PCR) test, not previously used on formed stool, as a screening tool for colonization.
Infection Versus Colonization
The testing method used to identify C. diff is critical for determining actual infection as opposed to colonization. Although identifying the presence of toxigenic C. diff is important, the presence of toxin A or B is the determining factor to diagnose infection. Those toxins translocate into the endothelial cells, where they destroy the colonic membrane.
When we conducted our study, our laboratory used only PCR testing; hence, we were unable to differentiate colonization from infection. After identifying our patients’ colonization rate and the number who developed diarrhea and required testing during their hospitalization, we began testing our hematology population upon admission. Once we were able to identify colonized patients, our unit’s hospital-acquired C. diff rate dropped by approximately 50%. Our rates of colonization and hospital-acquired infection have remained relatively consistent for 4.5 years while using this protocol. Two-step specimen PCR testing for toxigenic C. diff followed by reflex testing for toxins A and B has now been implemented for diarrheal stools only.
Prevention and Management Strategies
C. diff spores are resistant to harsh environmental conditions, including alcohol-based hand sanitizer, and can live on surfaces for extended periods, so it is difficult to eradicate from healthcare environments. Frequent thorough cleaning procedures for high-touch surfaces using sporicidal agents, such as bleach, and tools, such as ultraviolet light, and good isolation practices are critical to protecting patients from cross-transmission.
Much of the research that identified the high rate of colonization in the hematology and oncology population also showed that 13.3%–87.5% of colonized patients went on to develop C. diff infection during their hospital stay (see sidebar). Identifying colonization earlier in a patient’s hospitalization can help to optimize care. Many patients receiving chemotherapy, immunotherapy, and radiation therapy develop diarrhea secondary to treatment. If we know that the patient is not colonized and they have no other symptoms of colonic infection, they can begin antidiarrheal medications earlier, providing symptom relief and reducing the risk of developing fluid and electrolyte imbalances. Conversely, if the patient is colonized with C. diff, we can consider retesting for the toxin or even beginning antimicrobial therapy if they have additional signs of infection.
In 2021, the Infectious Diseases Society of America published an updated guideline focused on evidence-based recommendations for the treatment of C. diff. Although oral vancomycin is still identified as acceptable therapy, fidaxomicin is now the recommended therapy for initial infection because it is associated with a higher sustained clinical response, which is especially beneficial for immunocompromised patients such as the hematology and oncology population. Similarly, fidaxomicin is the recommended agent for treatment of recurrent C. diff infections, but vancomycin is an acceptable alternative.
Two other therapies are mentioned as treatments for recurrent C. diff infections:
- Fecal microbiota transplantation uses stool from a donor to restore a healthy gut microbiome with the intent to reduce the overgrowth of C. diff.
- Bezlotoxumab is a monoclonal antibody which binds to toxin B, implicated in both the virulence and recurrence of C. diff disease.
C. diff can cause potentially serious infections, especially in the hematology and oncology population. Understanding the difference between colonization and infection, infection control measures, and treatment options is essential for those providing care for patients with cancer.