GI Infections: GI Infections: Recurrent Clostridioides difficile

0:00Welcome to Board Pearls. This is episode two of five of the GI Infections chapter, in the Special Populations and Acute or Supportive Care module. This episode is recurrent Clostridioides difficile infection, one recurrence at a time, followed in the woman from episode one. Her first recurrence shows why the infection returns after the drug stops, why the drug used last time decides the drug used now, and what a taper and pulse does. Her second recurrence shows when fecal microbiota therapy comes in, how it's given, and what the two approved products are. Her next antibiotic shows when prophylaxis helps, and her history shows what happened to bezlotoxumab and how recurrence is told apart from irritable bowel syndrome.

0:41Here's the patient. She's the eighty-one-year-old woman in long-term care from episode one, whose severe infection after clindamycin was treated with ten days of fidaxomicin. Five weeks after finishing, her watery diarrhea returns, six stools a day with cramping, off laxatives. Her nucleic acid amplification test, NAAT, and toxin enzyme immunoassay, EIA, are both positive.

1:05She has a first recurrence of Clostridioides difficile infection, CDI. Recurrence is a return of disease within eight weeks of completed therapy, and hers came at five weeks, with symptoms and a positive toxin test. A first recurrence affects twenty to thirty percent of treated patients, and the risk exceeds sixty percent after a third episode, so preventing recurrence is the central problem of this disease.

1:30Her infection came back because spores survived. Spores aren't killed by the antibiotic, and once the drug stops, they germinate into vegetative bacteria that re-establish disease. So every second-line regimen aims to keep drug concentrations in the colon above the killing threshold across several rounds of germination, so that each new wave of vegetative bacteria dies before it can take hold. Switching drugs deals with possible resistance and uses a spectrum that may spare more of the normal flora, and pulsing the dose deals with the germination cycle directly.

2:02What she received last time decides what she receives now. After a first recurrence that followed metronidazole or vancomycin, fidaxomicin is preferred. After a recurrence that followed fidaxomicin, a vancomycin taper and pulse is recommended. Her first episode was treated with fidaxomicin, so repeating it would repeat the drug that just failed to hold her spores. She gets the vancomycin taper and pulse.

2:28Her taper and pulse follows a set schedule: vancomycin one hundred twenty-five milligrams four times daily for ten to fourteen days, then twice daily for seven days, then once daily for seven days, then every two to three days for two to eight weeks. In pooled meta-analyses, a taper followed by pulses beats either a taper alone or pulses alone, because the falling doses and then the pulses keep drug in the lumen across germination cycles, with each pulse catching bacteria that germinated since the last dose. Her course lasts roughly six to eleven weeks in all, built around her spores rather than her symptoms.

3:07Had her first episode been treated with vancomycin, her first recurrence would have gone the other way, to fidaxomicin. She'd get either the standard ten days at two hundred milligrams twice daily or an extended-pulse regimen: two hundred milligrams twice daily for five days, then every other day on days seven through twenty-five. In a randomized trial, the extended pulse lowered recurrence by about thirteen percentage points at day fifty-five compared with standard vancomycin, because its alternate-day phase covers the germination window. Each drug has a pulsed form, and the choice depends on which one failed, so the first thing read in her chart is the name of her last drug.

3:46At this point she'd once have been a candidate for bezlotoxumab, a monoclonal antibody against toxin B given once alongside the antibiotic course. It reduced twelve-week recurrence by about ten percentage points, most in patients over sixty-five or with prior CDI, immunocompromise, or severe disease. It was discontinued in the United States on January thirty-first, twenty twenty-five, for business reasons. It still appears in older guidelines, and it was always an adjunct to antibiotics, never a treatment on its own.

4:20Then she recurs again. Four weeks after her last pulse, her diarrhea returns with a positive toxin test, her second recurrence and third episode.

4:29After two or more recurrences following appropriate antibiotic courses, her next step is fecal microbiota therapy, FMT, rather than a third antibiotic course. FMT achieves sustained cure in about eighty to ninety percent of these patients, far more often than repeat antibiotics, and randomized trials comparing it with fidaxomicin and vancomycin favored FMT. It works because it restores the normal colonic flora that antibiotics strip away, the flora that normally keeps spores from re-establishing disease.

5:01Her therapy follows a sequence. Her symptoms are controlled first with vancomycin, four times daily for ten to fourteen days, then tapered to the lowest effective dose, and she's referred to an established program. FMT is delivered by colonoscopy, which has the most evidence, by capsule, or by enema. Donor screening under Food and Drug Administration, FDA, enforcement guidance is mandatory, covering extended-spectrum beta-lactamase-producing E. coli, Shiga toxin-producing E. coli, multidrug-resistant organisms, viral pathogens, and SARS-CoV-2. That's why FMT comes from a program and never from a family member's sample prepared at home.

5:42She could instead receive one of the two FDA-approved live biotherapeutic products, which have standardized what was a variable practice. Rebyota, fecal microbiota, live-jslm, is a single rectal dose given after a standard antibiotic course for recurrent CDI, approved in twenty twenty-two. Vowst, fecal microbiota spores, live-brpk, is an oral spore preparation taken after a standard course, approved in twenty twenty-three. Both achieve cure rates comparable to traditional FMT in adults with at least one recurrence after a previous episode, and the American College of Gastroenterology, ACG, endorses live biotherapeutics for a second or later recurrence. At eighty-one and in long-term care, she can avoid a colonoscopy with the oral product, or avoid both a scope and a course of capsules with the single rectal dose. Either one follows her antibiotic course and never replaces it.

6:37Three months after microbiota therapy, she needs an antibiotic for a urinary tract infection, and that brings her risk back. In patients with prior CDI, oral vancomycin prophylaxis during antibiotic exposure reduces recurrence, with a pooled odds ratio of about zero point three four. In patients without prior CDI, it shows no significant benefit and isn't recommended. With three episodes behind her, she takes oral vancomycin alongside her urinary antibiotic. If her culture allows, she also avoids the highest-risk classes, clindamycin, fluoroquinolones, third-generation cephalosporins, and broad-spectrum penicillins, which strip the flora her therapy restored. The man from episode one, with a discordant result that most likely meant colonization and no confirmed CDI, wouldn't get prophylaxis.

7:29Each new episode of diarrhea in her is confirmed carefully before it's called a recurrence. She isn't retested after symptoms resolve from any course, because up to half of treated patients still carry detectable nucleic acid, and because post-infection irritable bowel syndrome, which affects about a quarter of patients after CDI, can mimic recurrence. A recurrence is first defined by symptoms, three or more unexplained watery stools a day off laxatives, and only then tested.

7:57Here are the traps the boards set in these patients. Repeating fidaxomicin after a recurrence that followed fidaxomicin. Using a short vancomycin course instead of a taper and pulse. Forgetting the extended-pulse fidaxomicin regimen. Offering bezlotoxumab, which is discontinued in the United States, or offering it on its own. Giving a third antibiotic course instead of microbiota therapy after two recurrences. Giving a live biotherapeutic without first completing an antibiotic course. Using an unscreened donor. Giving vancomycin prophylaxis to a patient without prior CDI. And mistaking post-infection irritable bowel syndrome for recurrence.

8:37So, start to finish. Recurrence within eight weeks reflects regrowth from surviving spores, so second-line regimens keep drug in the colon across germination cycles. A first recurrence after metronidazole or vancomycin gets fidaxomicin, standard or extended-pulse, and a recurrence after fidaxomicin gets the vancomycin taper and pulse. Bezlotoxumab is no longer available in the United States and was only ever an adjunct.

9:04After two or more recurrences, symptoms are controlled with antibiotics and then microbiota therapy is given: screened-donor FMT, rectal Rebyota, or oral Vowst, with sustained cure in about eighty to ninety percent. Patients with prior CDI get oral vancomycin prophylaxis during later antibiotic courses. And recurrence is defined by symptoms before testing, because post-infection irritable bowel syndrome can mimic it.

9:30Episode three is travelers' diarrhea, the bacterial causes of bloody diarrhea, the host-specific bacteria, and the food toxins.

9:38For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode two of five of chapter thirty-three, and I'll see you in the next one.