Is there a difference in efficacy between using vancomycin oral liquid vs capsules in treating C. diff infection?

Comment by InpharmD Researcher

Limited evidence exists comparing clinical efficacy of vancomycin compounded oral liquid and capsules for the management of Clostridioides difficile infection (CDI). Current American College of Gastroenterology (ACG) guidelines do not recommend one formulation over the other. One retrospective study found no difference between the two formulations in 30-day mortality, recurrence, or complications when used for severe CDIs.

Background

According to the 2021 American College of Gastroenterology guidelines, oral vancomycin is recommended for treating an initial episode of severe or non-severe Clostridioides difficile infection (CDI) and fulminant CDI or preventing further recurrences in high-risk populations. However, the guidelines do not provide additional recommendations regarding a specific oral formulation of vancomycin. [1]

An Open Forum Infectious Diseases poster abstract from 2014 assessed clinical outcomes between oral vancomycin capsules and oral vancomycin compounded solution for the treatment of CDI. A retrospective review was conducted, which included 34 adult inpatients (50% male; median age of 62 years) who received oral vancomycin capsules or solution for ≥ 48 hours for the treatment of severe or severe-complicated CDI. The authors reported similar clinical cure rates in patients receiving oral vancomycin capsules and solution (74% versus 67%, respectively; odds ratio [OR] 1.40, 95% confidence interval [CI] 0.32 to 6.16, p= 0.7176). Three patients in the oral vancomycin solution group had CDI recurrences compared to zero patients treated with oral capsules (OR 0.08, 95% CI 0 to 1.78, p= 0.0667). Limited information acquired from the abstract may limit the clinical application of study results. [2]

References:

[1] Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections [published correction appears in Am J Gastroenterol. 2022 Feb 1;117(2):358]. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
[2] Saleh R, Sam S, Russell L, Jungsuwadee P, Cluxton D, Mersch A. 1652: Retrospective Comparision of Oral Vancomycin Capsules vs Oral Vancomycin Solution for the Treatment of Severe Clostridium Defficile Infection. Open Forum Infect Dis. 2014;1(Suppl 1):S441-S442. doi:10.1093/ofid/ofu052.1198
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there a difference in efficacy between using vancomycin oral liquid vs. capsules in treating C.diff infection?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

 

Comparison of Oral Vancomycin Capsule and Solution for Treatment of Initial Episode of Severe Clostridium difficile Infection

Design

Retrospective, noninterventional cohort study

N= 76

Objective

To determine treatment outcome differences for Clostridium difficile infection (CDI) based on oral vancomycin formulation,  commercially available capsule versus compounded oral solution

Study Groups

Vancomycin solution (n= 25)

Vancomycin capsule (n= 50)

Inclusion Criteria

Patients diagnosed with severe CDI who received oral vancomycin for at least 72 hours; evidence of diarrhea on the day of a stool sample positive for C difficile toxin based on enzyme-linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR) testing; diarrhea when following thresholds were met or exceeded within 24 hours: 3 unformed stools, 200 mL watery rectal bag output, or 1 L colostomy output; severe CDI characterized based on white blood cell (WBC) count of at least 15 x 103 cells/mL and serum creatinine (SCr) of at least 1.5 times premorbid level; patients with unknown baseline kidney function, and inpatient documentation of acute kidney injury

Exclusion Criteria

Mild-moderate CDI, severe complicated CDI, recurrent CDI, and baseline conditions affecting stool output, including irritable bowel disease, graft versus host disease, neutropenia, and cirrhosis

Methods

Eligible patients were divided into two cohorts, one receiving compounded vancomycin oral solution and the other receiving commercially available vancomycin capsules. Relevant data were retrospectively collected through the electronic and paper medical record by a single coinvestigator. Progression notes were evaluated for symptoms of CDI and evidence of complications, such as toxic megacolon. Clinical cure was defined as resolution of diarrhea for 48 hours (passage of ≤ 2 formed stools, < 1 L colostomy output, or < 200 mL rectal bag in 24 hours) without the development of a complication.

Duration

Between July 2006 and July 2011

Outcome Measures

Primary: time to clinical cure of CDI

Secondary: clinical cure rate at day 10 after CDI onset, mortality rate within 30 days of treatment, CDI-associated complication rates within 10 days, and recurrence rate within 30 days

Baseline Characteristics

  

Vancomycin solution (n= 25)

Vancomycin capsule (n= 51)

  

Age, years

 64 (58 to 77) 68 (59 to 73)  

Values on day 1 of CDI

Number of loose stools

WBC count, 103 cells/μL

Lactate, mmol/L

CCI score 

SOFA score 

 

4 (4 to 8)

19.1 (16.6 to 24.8)

1.5 (0.9 to 2.1)

2 (1 to 3)

3 (2 to 5)

 

4 (3 to 6)

17.2 (15.4 to 25.0)

0.6 (0 to 1.2)

3 (2 to 5)

2 (1 to 3)

  

Combination with metronidazole

 16 (64%)  26 (51%)  

Vancomycin

Duration

Dose

 

10 (8.5 to 10)

1,000 (721 to 1,737) 

 

10 (9 to 10)

888 (500 to 1,000)  

  

Concomitant antibiotic use

 21 (84%) 38 (75%)  

Concomitant probiotic use

 0 1 (2%)   

No significant differences were noted in baseline characteristics between the two groups, except for lactate levels (p< 0.001). 

Ordinal and continuous data were reported as median (IQR).

CCI, Charlson comorbidity index; SOFA, Sequential Organ Failure Assessment; IQR, Interquartile range

Results

Endpoint

Vancomycin solution (n= 25)

Vancomycin capsule (n= 51)

p-value

30-Day mortality

5 (20%)

 6 (12%) 0.338

Recurrence within 30 days

 1 (4%) 2 (4%) 1.0

Complications

Toxic megacolon 

Colectomy 

Colonic perforation 

Ileus 

 

1 (4%)

2 (8%)

1 (4%)

0

 

2 (4%)

2 (4%)

0

3 (6%)

 

1.0

0.594

0.329

0.547

Adverse Events

 N/A 

Study Author Conclusions

Presented data suggest that, for patients with an initial episode of severe CDI, the use of a compounded oral solution of vancomycin had no observed difference in rates of clinical cure, time to clinical cure, or development of complications from CDI compared with commercially available capsules. For reasons of economy, hospitals may decide to prepare oral vancomycin solution rather than purchase manufactured vancomycin capsules.

InpharmD Researcher Critique

The study did not recruit the predefined number of patients and thus was underpowered to determine a potentially significant difference in the primary endpoint between the two formulations. Additionally, the study was limited by its retrospective design and inaccurate documentation of healthcare records. 



References:

Bass SN, Lam SW, Bauer SR, Neuner EA. Comparison of oral vancomycin capsule and solution for treatment of initial episode of severe Clostridium difficile Infection. J Pharm Pract. 2015;28(2):183-188. doi:10.1177/0897190013515925