Advances in Microbiome-Based Therapies for Recurrent C difficile Infection - Episode 2
Joseph Reilly, BS, PharmD, BCGP; Candace Cotto, RN; and Andrew Skinner, MD, review C. difficile infection (CDI), its risk factors, symptoms, and quality of life for the patient.
Stuart Johnson, MD: Candace, what is Clostridoides difficile, and how do people get C difficile infection [CDI]?
Candace Cotto, RN: C difficile is a gram-positive spore-forming bacteria that causes inflammation in the colon. The C diff spores germinate into cells that can produce toxins A and B, and patients unfortunately get it transmitted by hand to mouth, by fecal contamination, or on a surface that they may have touched that is contaminated with feces containing the spores from C difficile.
Stuart Johnson, MD: Which patients are at increased risk for CDI?
Candace Cotto, RN: There are 3 different factors, environment, demographics and medications. As far as demographics, this includes patients who are over age 65, it’s more prevalent in women, and also patients who are immunocompromised. As far as medications, as we mentioned, antibiotics, the most common ones would be amoxicillin, cephalosporins, piperacillin, and clindamycin. Then as far as environment, this includes patients who are frequently hospitalized, and those who live in skilled nursing facilities.
Stuart Johnson, MD: Thank you. Andrew, could you describe the symptoms of CDI in patients with mild, moderate, or severe CDI?
Andrew Skinner, MD: Yes. C difficile infections can come in different varieties. We have the mild to moderate form, and one of the things we look for is 3 or more loose bowel movements over a period of 48 hours or more. When we start talking about severe infections, we do start to include laboratory counts such as a white blood cell count greater than 15,000, or a creatinine greater than 1.5 [mg/dL], If we look at the IDSA [Infectious Diseases Society of America] guidelines from 2017.
Stuart Johnson, MD: And how is it diagnosed?
Andrew Skinner, MD: This is a tricky question at this point right now, there’s a bit of a change we’re seeing with some of the diagnostic patterns. More frequently we’ve been using the PCR [polymerase chain reaction] to diagnose, but one of the issues we’ve run into with PCR is it’s an overly sensitive test, where we will end up picking up a lot of the bacteria that may not be clinically relevant to us. So there’s been a larger push more recently to start incorporating these toxin immunoassays on top of the PCR. We’re taking an algorithmic approach toward a diagnosis of C difficile at this time, which is, again, in line with the 2017 guidelines from the IDSA and SHEA [Society for Healthcare Epidemiology of America] as well.
Stuart Johnson, MD: Joseph, how would inappropriate excessive use of antibiotics contribute to the development of CDI in hospitalized patients in particular?
Joseph Reilly, BS, PharmD, BCGP: That’s a good question. It certainly does contribute, most of us associate the development of CDI with antibiotic use. A healthy microbiome inhibits pathogen colonization through competitive exclusion. The bacteria located in our colon produce…and antibacterial compounds that prevent C diff from colonizing and causing subsequent infection. So when we take antibiotics that have broad spectrum coverage, such as we said, clindamycin is one, or quinolones, or Zosyn, they inhibit a lot of anaerobic bacteria that are essential in our microbiome. When we do this, it allows opportunistic pathogens such as C diff to colonize and grow, and develop into infectious disease, C diff diarrhea.
Stuart Johnson, MD: Thank you. There is evidence that asymptomatic carriers have contributed to C difficile transmission and hospital onset CDI in inpatient facilities. Andrew, how common is asymptomatic colonization in with C difficile?
Andrew Skinner, MD: There was a recent paper by Scott Curry, [MD,] in 2023 from Clinical Infectious Diseases, and one of the findings is that roughly 10% of those in the health care setting were asymptomatically colonized by C difficile. And about 61% of those ended up being transient carriers. So these are people with a low burden of bacteria, intended to clear relatively quickly. The other interesting finding is that the majority of the patients who ended up developing a C difficile infection were those who had screened negative initially. Some of the limitations from that could have been from the fact that they were only screening once a once a week at that point. There very well could be some transmission within the hospital from these asymptomatic carriers to others.
Stuart Johnson, MD: That’s an interesting point that most of the patients with clinical C difficile infection were negative before they showed up with C difficile diarrhea. How do you explain that?
Andrew Skinner, MD: Again, some of that comes back to the point that they were only screening once a week at this point, and so they were likely missing some of these people who were transmitting within the hospital. That’s likely why there was a bit of a gap there.
Stuart Johnson, MD: Candace, how does recurrent CDI affect a person’s quality of life, their health, their ability to work and care for themselves, their ability to participate in daily activities?
Candace Cotto, RN: Most of the patients are not able to work. They’re not able to go around their friends and family for fear of perhaps giving it to them. They can have multiple episodes of diarrhea a day. They’re afraid of going to work, unexpected diarrhea episodes. They often become depressed, withdrawn, they isolate themselves, and it’s a horrible cycle they get themselves into.
Transcript edited for clarity