Oral vancomycin treatment does not alter postprandial inflammation in lean and obese, metabolic syndrome subjects

Vancomycin is frequently used for the treatment of C. difficile infections (CDI). There are concerns that this might increase the risk of selecting vancomycin resistant enterococci (VRE). Here, we evaluated whether there is an increased risk of VRE acquisition following vancomycin for CDI specific treatment. Patients with CDI, metronidazole, or oral vancomycin treatment and without preexisting VRE were monitored for VRE acquisition. VRE isolates from patients with acquired and preexisting colonization were collected and subjected to whole genome sequencing. In total, 281 patients (median age 56 years, 54% of the male sex) presented with toxin positive C. difficile. Of them, 170 patients met the inclusion criteria, comprising 37 patients treated with metronidazole and 133 treated with oral vancomycin. In total, 14 patients meeting the inclusion criteria acquired VRE (vancomycin: n = 11; metronidazole: n = 3). Statistical analysis revealed no significant differences between both VRE acquisition rates. Genetic comparison of detected VRE isolates resulted in eight clusters of closely related genotypes comprising acquired and preexisting strains. Our results suggest that vancomycin and metronidazole likewise increase the risk of VRE acquisition. Genetic comparison indicates that VRE acquisition is a result of both antibiotic selection and pathogen transmission.

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Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients

mSphere ◽

10.1128/msphere.00936-20 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Skye R. S. Fishbein ◽

Tiffany Hink ◽

Kimberly A. Reske ◽

Candice Cass ◽

Emily Struttmann ◽

...

Keyword(s):

Environmental Contamination ◽

Controlled Trial ◽

Nucleic Acid Amplification ◽

Oral Vancomycin ◽

Antibiotic Resistant ◽

Content Type ◽

Randomized Controlled ◽

Clostridioides Difficile ◽

Vancomycin Resistant ◽

Vancomycin Treatment

ABSTRACT Clostridioides difficile infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with C. difficile unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin (n = 8) or placebo (n = 7). C. difficile and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with C. difficile posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity (P = 0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes (P = 0.037) increased after treatment; C. difficile and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear C. difficile, and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.) IMPORTANCE A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease C. difficile shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of C. difficile, perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of C. difficile/ARO-related outcomes and transmission.

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Lack of Increased Colonization with Vancomycin-Resistant Enterococci during Preferential Use of Vancomycin for Treatment during an Outbreak of Healthcare-Associated Clostridium difficile Infection

Infection Control and Hospital Epidemiology ◽

10.1086/653613 ◽

2010 ◽

Vol 31 (7) ◽

pp. 710-715 ◽

Cited By ~ 17

Author(s):

Mark Miller ◽

Lisa Bernard ◽

Melissa Thompson ◽

Daniel Grima ◽

Jocelyne Pepin

Keyword(s):

Clostridium Difficile ◽

Oral Vancomycin ◽

Outbreak Period ◽

Vancomycin Resistant Enterococci ◽

Period 2 ◽

Jewish General Hospital ◽

Vancomycin Resistant ◽

Healthcare Associated ◽

Vancomycin Treatment ◽

Oral Metronidazole

Objective.To assess whether use of oral vancomycin for treatment during an outbreak of Clostridium difficile infection (CDI) was associated with increased rates of colonization with vancomycin-resistant enterococci (VRE)..Design.A retrospective analysis of hospital databases.Setting.The Jewish General Hospital in Montreal, Quebec, Canada.Methods.We collected data regarding VRE colonization and CDI from November 1, 2000, through September 30, 2007, during which policies of preferential oral metronidazole or vancomycin treatment were implemented to control an outbreak of CDI. Four periods were considered: period 1, the preoutbreak period when metronidazole was used; period 2, the CDI outbreak period when metronidazole was used; period 3, the postoutbreak period when vancomycin was used; and period 4, the postoutbreak period when metronidazole was used.Results.A total of 2,412 cases of CDI and 425 cases of VRE colonization were identified. The rate of CDI increased significantly during period 2 and decreased to preoutbreak levels during period 3. The rate of VRE also increased during period 2 and decreased during the first 18 months of period 3. A clonal outbreak of cases of VRE (VanA) colonization was observed toward the end of period 3 and into period 4. Excluding the period of the clonal outbreak, there was a strong correlation between the number of cases of CDI and VRE colonization (r = 0.736; P = .001) and a negative association between VRE colonization and vancomycin use (r = —0.765; P = .04).Conclusions.Increased vancomycin use was not associated with an increase in VRE colonization over a 2-year period. Restriction of vancomycin use during CDI outbreaks because of the fear of increasing VRE colonization may not be warranted.

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Both Oral Metronidazole and Oral Vancomycin Promote Persistent Overgrowth of Vancomycin-Resistant Enterococci during Treatment of Clostridium difficile-Associated Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00090-08 ◽

2008 ◽

Vol 52 (7) ◽

pp. 2403-2406 ◽

Cited By ~ 170

Author(s):

Wafa N. Al-Nassir ◽

Ajay K. Sethi ◽

Yuejin Li ◽

Michael J. Pultz ◽

Michelle M. Riggs ◽

...

Keyword(s):

Clostridium Difficile ◽

Prospective Observational Study ◽

Oral Vancomycin ◽

The Past ◽

Vancomycin Resistant Enterococci ◽

Stool Samples ◽

Vancomycin Resistant ◽

Healthcare Associated ◽

Vancomycin Treatment ◽

Oral Metronidazole

ABSTRACT For treatment of mild to moderate Clostridium difficile-associated disease (CDAD), oral metronidazole has been recommended as the preferred agent, in part due to concern that vancomycin may be more likely to promote colonization by vancomycin-resistant enterococci (VRE). We performed a prospective observational study to examine the effects of oral metronidazole or vancomycin treatment of CDAD on acquisition and concentration of VRE stool colonization. Before, during, and after 90 courses of CDAD therapy, stool samples were cultured for VRE, and the concentrations were quantified. Eighty-seven subjects (97%) had received antibiotics within the past month. For 56 treatment courses in which preexisting VRE colonization was present, metronidazole (n = 37 courses) and vancomycin (n = 19 courses), each promoted persistent VRE overgrowth during therapy, and the concentration decreased significantly in both groups by ∼2 weeks after completion of treatment (P <0.049). For 34 treatment courses in which baseline cultures were negative for VRE, new detection of VRE stool colonization occurred during 3 (14%) of the 22 courses of metronidazole and 1 (8%) of the 12 courses of vancomycin (P = 1.0). These results demonstrate that both oral metronidazole and oral vancomycin promote the overgrowth of VRE during treatment of CDAD. New CDAD treatments are needed that are less likely to disrupt the intestinal microflora and promote overgrowth of healthcare-associated pathogens.

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ORAL VANCOMYCIN: TREATMENT OF PRIMARY SCLEROSING CHOLANGITIS IN CHILDREN

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-199710000-00166 ◽

1997 ◽

Vol 25 (4) ◽

pp. 479 ◽

Cited By ~ 1

Author(s):

K L Cox ◽

K M Cox

Keyword(s):

Primary Sclerosing Cholangitis ◽

Sclerosing Cholangitis ◽

Oral Vancomycin ◽

Vancomycin Treatment

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Comparative Effectiveness of Vancomycin vs. Metronidazole in Mild Clostridium difficile Infections, and Potential Impact on Subsequent Vancomycin-Resistant Enterococcus (VRE) Isolation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.966 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S388-S388

Author(s):

Ilan Youngster ◽

Zipora Lazarovitch ◽

Marina Bondorenco ◽

Betlehem Mengesha ◽

Limor Toledano ◽

...

Keyword(s):

Clostridium Difficile ◽

Cox Regression ◽

Prediction Score ◽

Vancomycin Resistant Enterococcus ◽

Oral Vancomycin ◽

Individual Patient Level ◽

Patient Level ◽

Vancomycin Resistant ◽

Potential Impact ◽

Vancomycin Treatment

Abstract Background The epidemiology and clinical characteristics of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI, with superior cure rates observed in comparative trials. However, controlled comparative efficacy data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent Vancomycin-Resistant Enterococcus (VRE) isolation rates remains unknown at the individual patient level. Methods A Retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, Israel, from 2010 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs..metronidazole was evaluated in the subset of patients with mild CDI. The outcomes of patients, who received vancomycin or metronidazole (but not both), were compared by Cox regression. A prediction score was used to control for possible confounders associated with being treated with vancomycin. The independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation was analyzed using Cox regression. Results A total of 413 patients with CDI were included in the study. The majority were elderly (median age 75 years, range 19–120), and had extensive comorbidities (mean Charlson’s combined condition score 6.7 ± 3.4) and significant acute illness indices (35% with severe to fulminant Horn index). Among 126 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a “vancomycin case”. Ten patients had new post-CDI VRE isolation. In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=6.7, P = 0.04). Conclusion Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis. Disclosures All authors: No reported disclosures.

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