Date Published: 1/12/2025
For the treatment of initial non-severe C. difficile infection, clinicians should consider either oral vancomycin 125mg four times daily for 10 days or fidaxomicin 200mg twice daily for 10 days as first-line treatments. While metronidazole is no longer the primary choice, it may still be considered for non-severe cases if cost or access to vancomycin is limited. It's worth noting that vancomycin has demonstrated superior cure rates compared to metronidazole, with 79% versus 72% effectiveness in non-severe cases. Additionally, while fidaxomicin shows similar initial cure rates to vancomycin, it boasts significantly lower recurrence rates. The minimum duration of treatment should be 10 days, but it can be extended based on the patient's clinical response. Lastly, any concurrent antibiotics should be discontinued when possible, as they can heighten the risk of treatment failure.
When testing for C. difficile, a two-step algorithm is crucial to differentiate between colonization and active infection. This approach involves combining a highly sensitive test, such as GDH or NAAT, with a highly specific toxin EIA test. It's important to remember that C. difficile colonization is found in 4-15% of healthy adults and can be as high as 21% of hospitalized patients. While PCR/NAAT detects the gene for toxin production, it doesn't confirm whether the toxin is actively being produced. GDH testing is highly sensitive but can detect both toxigenic and non-toxigenic strains. Conversely, Toxin EIA has high specificity but lower sensitivity, which may lead to false negatives. Finally, a test of cure is generally not recommended as patients may continue to test positive even after clinical resolution.
For patients experiencing two or more recurrences of C. difficile infection, fecal microbiota transplantation (FMT) is the recommended treatment for preventing further recurrences. Clinical trials have demonstrated an impressive 90% success rate for FMT in this context. The delivery methods for FMT include colonoscopy, capsules, or enema, with colonoscopic delivery showing the highest efficacy. Following a successful FMT, patients should experience resolution of diarrhea within 3 days. However, factors such as ongoing antibiotics, severe CDI, and IBD may increase the risk of FMT failure. Follow-up testing for C. difficile is not typically recommended unless symptoms recur.
The severity of C. difficile infection is defined by specific criteria, which significantly impact the treatment approach and prognosis. Severe CDI is characterized by a WBC of ≥15,000 cells/mm³ or a creatinine >1.5 mg/dL, while fulminant CDI includes the severe criteria along with hypotension/shock, ileus, or megacolon. For severe CDI, the initial treatment involves either vancomycin 125mg QID or fidaxomicin 200mg BID. However, fulminant CDI necessitates a more aggressive approach with vancomycin 500mg QID plus IV metronidazole. In addition, early surgical consultation is recommended for fulminant cases with poor response to medical therapy.
Bezlotoxumab, a human monoclonal antibody targeting C. difficile toxin B, can be a useful tool in preventing CDI recurrence in high-risk patients. This approach is especially beneficial for patients with at least one risk factor such as age ≥65, immunocompromised status, or a prior CDI episode. Administered as a single IV infusion during standard antimicrobial treatment, bezlotoxumab reduces CDI recurrence by approximately 40% compared to placebo. Due to cost considerations, careful patient selection is important. It is also important to note that bezlotoxumab does not treat active infection but prevents recurrence by neutralizing toxin B.
The relationship between C. difficile infection and inflammatory bowel disease (IBD) introduces unique diagnostic and therapeutic challenges. IBD patients have a significantly increased risk of developing CDI, about 4.8-fold higher. Therefore, testing should be performed during all IBD flares with diarrhea. It is recommended that IBD patients receive a minimum 14-day course of therapy, and immunosuppressive therapy should not be withheld during CDI treatment.
Oral vancomycin prophylaxis can be considered for patients with a history of CDI and who are at high risk of recurrence when systemic antibiotics are being used. A typical prophylactic dose is vancomycin 125mg once daily, and this should be continued until 5 days after completion of systemic antibiotics. This is most beneficial in patients that are ≥65 years old, have multiple previous CDI episodes, recent hospitalizations, or are immunocompromised. Prophylaxis should not replace other important preventive measures like antimicrobial stewardship.
Managing fulminant C. difficile infection demands a coordinated medical and potentially surgical approach, with specific indications and timing considerations. The medical therapy for fulminant CDI includes vancomycin 500mg q6h orally or via NGT, IV metronidazole 500mg q8h, vancomycin enemas (if ileus is present) and volume resuscitation. Surgical options include total colectomy with end ileostomy (traditional) or loop ileostomy with colonic lavage (newer). It is important to seek early surgical consultation for all fulminant cases, as mortality increases significantly if surgery is delayed until the development of shock or organ failure.
The role of proton pump inhibitors (PPIs) in C. difficile infection necessitates careful clinical decision-making about continuation or discontinuation. While PPI use is associated with a modest increase in CDI risk, at an odds ratio of 1.52, the risk is small compared to other factors. Therefore, PPIs should be continued if a clear indication exists, such as active ulcer disease, severe erosive esophagitis, Barrett's esophagus, or if a patient is a high-risk NSAID user. If a patient has mild GERD, switching to an H2 blocker after CDI may be appropriate, which gives the clinician an opportunity to reassess the necessity of PPI use during CDI treatment.
Immunocompromised patients require special consideration for the diagnosis, treatment, and prevention of CDI. These patients face a higher risk of initial CDI, increased recurrence rates, and higher mortality risks. Additionally, they may present with atypical symptoms. Specifically, transplant recipients have a 9-fold higher risk compared to the general population, those with hematologic malignancies are at a higher risk during neutropenia, HIV patients with a CD4 count <50 have an increased risk, and organ dysfunction impairs the response to treatment. These nuances require that clinicians be more vigilant when caring for immunocompromised patients.
Source
Kelly CR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021
https://pubmed.ncbi.nlm.nih.gov/34003176/
