Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients (original) (raw)
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Journal of the Canadian Association of Gastroenterology, 2020
Background Vancomycin is the recommended first-line therapy for mild to severe Clostridioides difficile infection (CDI). However, oral vancomycin is associated with disruption of the indigenous microbiota, predisposing patients to overgrowth of endogenous pathogens such as vancomycin-resistant enterococci. Aims The primary objective of the study is to examine the effect of the treatment regimens of CDI on the risk of infection with gram-negative organisms in adult patients treated for CDI. Methods A retrospective cohort study of 319 adult patients treated for CDI at Hamilton Health Sciences in the year 2015. A multivariate logistic regression analysis was performed to determine if oral vancomycin-based therapy is associated with an increased risk of infection with gram-negative organisms after adjustment for other factors. Results Eighty-one patients were excluded because of recurrent episodes of CDI within the same year or missing information. 238 patients were included in the fina...
Initial vancomycin for first episode non-severe Clostridium difficile infection
BackgroundClostridium difficile infection (CDI) is an important cause of nosocomial diarrhea. Given the discrepancy in current treatment guidelines for mild CDI, we sought to evaluate the use of first-line vancomycin for the treatment of non-severe infection.MethodsWe conducted a retrospective cohort study of all adult inpatients with first episode CDI at our institution from January 2013 to May 2018. CDI was defined as a positive C. difficile loop-mediated isothermal amplification assay, in conjunction with ≥3 type 5–7 stools on the Bristol stool scale. To evaluate the impact of first-line vancomycin treatment on adverse clinical outcomes in patients with first episode non-severe CDI, the initial vancomycin vs. initial metronidazole cohorts were first examined in an unadjusted logistic regression analysis for any combination of relapse, recurrence, and all-cause 30-day mortality, followed by an adjusted multivariable analysis.ResultsA total of 737 cases were included. Patients had ...
Clinical Infectious Diseases
During the past 4 decades, oral vancomycin has been a mainstay of Clostridioides difficile infection (CDI) therapy with no reports of treatment failure due to emergence of vancomycin resistance. However, C. difficile isolates with high-level phenotypic resistance to vancomycin have recently been reported in 3 distinct geographic regions. There is an urgent need for surveillance to determine if strains with reduced vancomycin susceptibility are circulating in other areas. In a Cleveland-area hospital, screening of 176 CDI stool specimens yielded no C. difficile isolates with reduced vancomycin susceptibility and highlighted the potential for false-positive results due to contamination with vancomycin-resistant enterococci. Additional studies are needed to clarify whether reduced vancomycin susceptibility is an emerging problem that will alter clinical practice. Clinicians should alert their health department if they observe a substantial increase in the frequency of vancomycin treatm...
Clostridioides difficile: diagnosis and treatments
BMJ, 2019
Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with t...
Impact of Delayed Oral Vancomycin for Severe Clostridium difficile Infection
Hospital Pharmacy, 2018
Background: Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (VAN) is known to be superior to treatment with metronidazole (MDZ). However, previous studies have not evaluated the impact on patients when oral VAN therapy is delayed after diagnosis of severe CDI. Materials and Methods: This was a single-center, retrospective study of adult patients who were diagnosed with severe CDI. The objective was to compare clinical outcomes for patients treated initially with oral VAN versus patients receiving delayed oral VAN after at least 48 hours of initial treatment with MDZ. The primary outcome was all-cause in-hospital mortality. Results: There were 101 patients who comprised the initial oral VAN group, while 20 patients comprised the delayed oral VAN group. There was no significant difference in all-cause in-hospital mortality for patients in the initial oral VAN treatment group compared to those who had delayed oral VAN therapy (4.95% vs 15.00%, P = 0.13). ...
2010
Background: Oral vancomycin (125 mg qid) is recommended as treatment of severe Clostridium difficile infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients. Methods: We recruited hospitalized adults suspected to have CDI for whom oral vancomycin (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3 times/day and levels were measured with the AxSYM fluorescence polarization immunoassay. Results: Fifteen patients (9 with confirmed CDI) were treated with oral vancomycin. Patients with ≥4 stools daily presented lower faecal vancomycin levels than those with a lower frequency. Higher doses of oral vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (> 2000 mg/L), which were 3 orders of magnitude higher than the MIC 90 of vancomycin against C. difficile. One patient receiving 125 mg qid had levels below 50 mg/L during the first day of treatment. Conclusions: Faecal levels of vancomycin are proportional to the dosage administered and, even in patients with increased stool frequency, much higher than the MIC 90 . Patients given the standard 125 mg qid dosage might have low faecal levels during the first day of treatment. A loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the standard dosage should be evaluated in larger studies, since it might be less disruptive to the colonic flora and save unnecessary costs.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012
Study Objective. To assess antibiotic treatment patterns and clinical outcomes of patients with Clostridium difficile infection (CDI) based on underlying severity of CDI disease. Design. Retrospective analysis of data from a prospective cohort study. Setting. Large tertiary care university hospital. Patients. One hundred forty-four patients (mean ± SD age 63 ± 17 yrs) with CDI who received metronidazole (intravenous or oral) or oral vancomycin as their initial therapy option between 2006 and 2008. Measurements and Main Results. Patients were stratified by severity of illness and treatment, and outcomes assessed were clinical response, relapse of disease, all-cause inpatient mortality, and length of hospital stay. Mildmoderate CDI disease was present in 85 patients (59%) and severe disease in 59 patients (41%). Overall, oral vancomycin was given to 16 patients (11%); use of this drug did not differ according to severity of infection. Among patients with severe disease, clinical success occurred in 32 (63%) of 51 patients given metronidazole and in all 8 patients (100%) given vancomycin (p=0.04). Inpatient mortality and hospital length of stay were lower in patients with severe CDI who were given oral vancomycin, although these results were not statistically significant. Conclusion. Oral vancomycin was not commonly used for severe CDI. An improved clinical response rate was observed in patients with severe CDI given oral vancomycin; this outcome supported results from clinical trials. Antibiotic stewardship teams could play a major role in providing guidance on CDI treatment based on severity.
JAMA internal medicine, 2017
Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI. This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016. Treatment with vancomycin or...