Emerging Treatment Options for Recurrent C. Difficile Infection - Episode 3

Timely Referral and Diagnosis of C. difficile Infection (CDI)

August 24, 2022
Paul Feuerstadt, MD

Thomas Lodise, PharmD, PhD

Teena Chopra, MD, MPH

Bincy Abraham, MD, MS

Drs. Abraham, Chopra and Feuerstadt discuss importance of timely referral and diagnostic methods to discern C. difficile infection (CDI).

Paul Feuerstadt, MD:Unfortunately, as you elucidated before, a lot of patients in the United States get infected with C [Clostridioides] difficile. It’s estimated that up to 500,000 people get diagnosed with this on an annual basis. It’s imperative to understand when and where patients should be treated. Bincy, can you walk us through with regard to when to refer from primary care to an infectious disease [physician] or a gastroenterologist?

Bincy Abraham, MD, MS: We’re all aware and we all agree that timely treatment of our patients is quite important. This is to improve clinical symptoms—their diarrhea, their abdominal pain—but also to prevent complications: toxic megacolon, perforation, and any that can necessitate even need for collecting an increased mortality for these patients. I truly believe that primary care physicians should be able to initiate treatment for C difficile infection, but if they’re refractory or not improving, they should be referred quite early. Those patients need to be referred to specialists such as us gastroenterologists or infectious disease physicians for advanced therapy, especially to confirm that their symptoms aren’t improving, that they’re truly from C difficile infection. In most cases that we also see postinfectious diarrheas, we need to differentiate that. If it’s truly C difficile, then we need to be able to change therapy or add on therapy to fix them.

Paul Feuerstadt, MD:I completely agree with you. For me as a clinician, and everybody on the panel, identifying patients who don’t have C difficile but are referred to us is essential. A study estimated that about 25% of all patients referred with C difficile infection have other underlying disorders. When I meet patients and I talk to them about their symptoms, I tell them that’s 1 reason I enjoy caring for patients with C difficile: I have to generate differential diagnoses and think my way through how they got here, what’s occurring, and how I might be able to best help them. Understanding that and thinking about that will enhance our ability and the clinician’s ability to identify which patients are appropriate for therapy, which patients are diagnosed properly, and how to treat recurrent disease. But to treat initial infection or recurrent disease, we have to go through an alphabet soup. It’s that simple. The alphabet soup is diagnosis. We have EIA [enzyme immunoassay], we have GDH [glutamate dehydrogenase], we have PCR [polymerase chain reaction]. Teena, can you walk us through this alphabet of information and tell us what the diagnostic tools are and what a good diagnostic algorithm looks like?

Teena Chopra, MD, MPH: As Tom mentioned, you want to know those risk factors in the patient. In the right clinical setting, the most important thing in the diagnosis is your clinical judgment. If a patient has more than 3 unfirm stools 24 hours in, within an inflammatory picture, with a high white blood cell count and a fever, that points to inflammatory diarrhea. You want to think of C difficile with those risk factors that Tom mentioned. Once you have that clinical judgment, you want to test with a multistep algorithm approach rather than a single step. You want to start with a more sensitive test using the PCR or the GDH. If that’s positive, you want to confirm with a toxin test. If the toxin is positive, there’s C difficile. If that’s negative, then you want to repeat the PCR if you started with the GDH, or you want to do the GDH if you started with the PCR. That algorithmic approach is to make sure you don’t overdiagnose. As you know, the toxin test—the PCR—is very sensitive, and there can be a false negative toxin assay. All the tests have their own advantages and disadvantages. You want to do a multistep algorithmic approach in the context of your clinical acumen.

Paul Feuerstadt, MD: That clinical contextualization is an important concept: understanding that patients are having formed stools, you shouldn’t be sending a stool assay for C difficile. Also, understanding that the PCR assay has a tendency to over diagnose C difficile. In that circumstance, the main epidemiological studies say that upward of half a million people on an annual basis are diagnosed with C difficile but corrected based on the tools used: EIA and GDH vs the PCR as a primary test, so we can best understand and compare incidences that have happened over time. Teena, what are some challenges in the diagnosis of C difficile?

Teena Chopra, MD, MPH: One challenge we face a lot of times is not being able to identify that this is C difficile. The inflammatory picture, the high white blood cell count—that can tell. The high creatinine can tell whether this is C difficile or not as well. Also, the other challenges are older adults. We were talking about older adults, how they’re immunosenescent, they cannot mount up an antibody response. Sometimes they don’t present with that high white blood cell count and fever, but they have diarrhea. That’s an added challenge to order the tests in those patients. Also, a lot of older patients are coming from nursing homes and long-term acute care facilities that may not have an on-site microbiology lab. There can be several challenges while you’re waiting for the right test to come back. Are you going to treat the patient based on your clinical judgment? Those are some of the big challenges we face. Also, when you enter the recurrent C difficile world, you can have a continuous positive PCR test sometimes, which can also be very challenging. Your clinical acumen really comes to your rescue.

Paul Feuerstadt, MD:And understanding specifically what you have available. A lot of individuals and clinicians don’t have a choice. They work within a health care system; they get the choice of a C difficile assay. Understanding what that assay is and what it can detect is really important. If you have a GDH or an EIA assay, you have to understand that if they’re both negative, you’re negative. If they’re both positive, you’re positive. And if they’re discordant, reflex to the PCR to decide. Whereas in an institution, or if the local lab sends only a PCR assay, you have to understand the importance of that clinical context. If the patient isn’t on a laxative or has 3 liquid stools in 24 hours, that plays an essential role.

Transcript edited for clarity