What is the role of Vancomycin (Vancomycin) in treating Clostridioides difficile (C. diff) infection?

From the Guidelines

Vancomycin is an acceptable alternative treatment for Clostridioides difficile (C. diff) infections, with a recommended dose of 125 mg given 4 times daily by mouth for 10 days for initial episodes, and a tapered and pulsed regimen for recurrent episodes. The treatment of C. diff infections depends on the severity of the disease and the number of recurrences. For an initial episode of non-severe C. diff infection, fidaxomicin is the preferred treatment, but vancomycin is an acceptable alternative 1. For severe infections or recurrent episodes, vancomycin is a recommended treatment option, with a dose of 125 mg given 4 times daily by mouth for 10 days, which may be extended to 14 days 1. In fulminant cases, higher doses of vancomycin (500 mg four times daily) may be used, sometimes with intravenous metronidazole 1.

• Key considerations for vancomycin treatment include:
  • Completion of the full treatment course, even if symptoms improve
  • Maintenance of adequate hydration throughout therapy
  • Monitoring for recurrence and adjustment of treatment as needed
  • Consideration of alternative treatments, such as fidaxomicin, for initial episodes or recurrent infections The most recent and highest quality study, published in 2021, provides guidance on the treatment of C. diff infections, including the use of vancomycin 1. This study recommends vancomycin as an alternative treatment for initial episodes and recurrent infections, and provides guidance on dosing and treatment duration. Overall, vancomycin remains an important treatment option for C. diff infections, particularly for severe or recurrent cases.

From the FDA Drug Label

Vancomycin Hydrochloride Capsules 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with C. difficile-associated diarrhea (CDAD) The bactericidal action of vancomycin against Staphylococcus aureus and the vegetative cells of Clostridium difficile results primarily from inhibition of cell-wall biosynthesis. Clostridium difficile: Isolates of C difficile generally have vancomycin MICs of <1 mcg/mL, however vancomycin MICs ranging from 4 mcg/mL to 16 mcg/mL have been reported. Vancomycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)]. Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates) associated with enterocolitis. Anaerobic gram-positive bacteria: Clostridium difficile isolates associated with C. difficile associated bacteria. Efficacy was assessed by using clinical success, defined as diarrhea resolution and the absence of severe abdominal discomfort due to CDAD, on Day 10. The results for clinical success for vancomycin hydrochloride-treated subjects in both trials are shown in Table 2. Table 2: Clinical Success Rates (Full Analysis Set) Clinical Success Rate95% Confidence Interval Vancomycin Hydrochloride % (N) Trial 181.3 (134)(74.4,88.3) Trial 280.8 (125)(73.5,88. 1)

Vancomycin is effective for the treatment of C. difficile-associated diarrhea (CDAD).

• The clinical success rate for vancomycin hydrochloride-treated subjects was 81.3% in Trial 1 and 80.8% in Trial 2.
• The median time to resolution of diarrhea was 5 days and 4 days in Trial 1 and Trial 2, respectively.
• Vancomycin has been shown to be active against most isolates of Clostridium difficile, with MICs generally <1 mcg/mL. 2

From the Research

Vancomycin for C. difficile Infection

• Vancomycin is a recommended treatment for initial episodes of non-severe C. difficile infection, along with fidaxomicin 3.
• The efficacy of vancomycin compared to fidaxomicin has been studied in several trials, with fidaxomicin often showing superior results in terms of clinical cure and recurrence rates 4, 5, 6.
• In patients receiving concomitant antibiotics for concurrent infections, vancomycin has been compared to fidaxomicin, with some studies showing similar rates of clinical cure and recurrence 7, while others show fidaxomicin to be more effective 4.
• The use of vancomycin is associated with a higher risk of recurrence compared to fidaxomicin, with a meta-analysis showing a 31% reduction in recurrence risk with fidaxomicin 6.
• Guidelines recommend against the use of metronidazole as first-line therapy for adults with C. difficile infection, instead recommending vancomycin or fidaxomicin 3.

Comparison with Fidaxomicin

• Fidaxomicin has been shown to be more effective than vancomycin in achieving clinical cure and preventing recurrence in several studies 4, 5, 6.
• In patients with initial episodes, first recurrences, and non-severe cases, fidaxomicin has been shown to be superior to vancomycin 5.
• However, in severe cases, fidaxomicin and vancomycin have been shown to have similar treatment outcomes 5.
• A systematic review and meta-analysis found fidaxomicin to be consistently associated with a lower risk of C. difficile recurrence than vancomycin 6.

Clinical Use

• Vancomycin is typically administered orally, with a recommended dose of 125 mg every 6 hours for 10 days 4.
• The use of vancomycin should be guided by clinical guidelines and antibiotic stewardship principles to minimize the risk of resistance and recurrence 3.
• In cases of recurrent C. difficile infection, fecal microbiota transplantation may be considered as a treatment option 3.