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1,066 results on '"Garey, Kevin W."'

11. Fusobacterium nucleatum Adheres to Clostridioides difficile via the RadD Adhesin to Enhance Biofilm Formation in Intestinal Mucus

Author

Engevik, Melinda A, Danhof, Heather A, Auchtung, Jennifer, Endres, Bradley T, Ruan, Wenly, Bassères, Eugénie, Engevik, Amy C, Wu, Qinglong, Nicholson, Maribeth, Luna, Ruth Ann, Garey, Kevin W, Crawford, Sue E, Estes, Mary K, Lux, Renate, Yacyshyn, Mary Beth, Yacyshyn, Bruce, Savidge, Tor, Britton, Robert A, and Versalovic, James

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Digestive Diseases, Infectious Diseases, Emerging Infectious Diseases, Oral and gastrointestinal, Infection, Good Health and Well Being, Adhesins, Bacterial, Bacterial Adhesion, Biofilms, Bioreactors, Clostridioides difficile, Clostridium Infections, Feces, Flagella, Fusobacterium nucleatum, Gastrointestinal Microbiome, HT29 Cells, Humans, Intestinal Mucosa, Mucin-2, MUC2, Mucus, Biofilm, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsAlthough Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation.MethodsTo create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips.ResultsC difficile was found to colonize and form biofilms on MUC2-coated coverslips, and 16S rRNA sequencing showed a unique biofilm profile with substantial cocolonization with Fusobacterium species. Consistent with our bioreactor data, publicly available data sets and patient stool samples showed that a subset of patients with C difficile infection harbored high levels of Fusobacterium species. We observed colocalization of C difficile and F nucleatum in an aggregation assay using adult patients and stool of pediatric patients with inflammatory bowel disease and in tissue sections of patients with CDI. C difficile strains were found to coaggregate with F nucleatum subspecies in vitro; an effect that was inhibited by blocking or mutating the adhesin RadD on Fusobacterium and removal of flagella on C difficile. Aggregation was shown to be unique between F nucleatum and C difficile, because other gut commensals did not aggregate with C difficile. Addition of F nucleatum also enhanced C difficile biofilm formation and extracellular polysaccharide production.ConclusionsCollectively, these data show a unique interaction of between pathogenic C difficile and F nucleatum in the intestinal mucus layer.

Published
2021

12. Redefining Clostridioides difficile infection antibiotic response and clinical outcomes

Author

Gonzales-Luna, Anne J, Skinner, Andrew M, Alonso, Carolyn D, Bouza, Emilio, Cornely, Oliver A, de Meij, Tim G J, Drew, Richard J, Garey, Kevin W, Gerding, Dale N, Johnson, Stuart, Kahn, Stacy A, Kato, Haru, Kelly, Ciaran P, Kelly, Colleen R, Kociolek, Larry K, Kuijper, Ed J, Louie, Thomas, Riley, Thomas V, Sandora, Thomas J, Vehreschild, Maria J G T, Wilcox, Mark H, and Dubberke, Erik R

Published
2023
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20. Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response.

Author

Eubank, Taryn A, Dureja, Chetna, Garey, Kevin W, Hurdle, Julian G, and Gonzales-Luna, Anne J

Subjects
CLOSTRIDIUM diseases, VIRAL load, RESEARCH funding, MICROBIAL sensitivity tests, CLOSTRIDIOIDES difficile, VANCOMYCIN resistance, TREATMENT effectiveness, DESCRIPTIVE statistics, VANCOMYCIN, LONGITUDINAL method, ODDS ratio, RESEARCH, CONFIDENCE intervals, DRUG tolerance
Abstract

Background Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR). Methods This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes. Results A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5–16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P =.031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P =.04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval,.28–.97]; P =.04). Conclusions Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort. [ABSTRACT FROM AUTHOR]

Published
2024
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24. A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response

Author

Okhuysen, Pablo C, primary, Ramesh, Mayur S, additional, Louie, Thomas, additional, Kiknadze, Nino, additional, Torre-Cisneros, Julian, additional, de Oliveira, Claudia Murta, additional, Van Steenkiste, Christophe, additional, Stychneuskaya, Alena, additional, Garey, Kevin W, additional, Garcia-Diaz, Julia, additional, Li, Jianling, additional, Duperchy, Esther, additional, Chang, Betty Y, additional, Sukbuntherng, Juthamas, additional, Montoya, Jose G, additional, Styles, Lori, additional, Clow, Fong, additional, James, Danelle, additional, Dubberke, Erik R, additional, and Wilcox, Mark, additional

Published
2024
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28. Fusobacteriumnucleatum Adheres to Clostridioides difficile via the RadD Adhesin to Enhance Biofilm Formation in Intestinal Mucus

Author

Engevik, Melinda A., Danhof, Heather A., Auchtung, Jennifer, Endres, Bradley T., Ruan, Wenly, Bassères, Eugénie, Engevik, Amy C., Wu, Qinglong, Nicholson, Maribeth, Luna, Ruth Ann, Garey, Kevin W., Crawford, Sue E., Estes, Mary K., Lux, Renate, Yacyshyn, Mary Beth, Yacyshyn, Bruce, Savidge, Tor, Britton, Robert A., and Versalovic, James

Published
2021
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29. Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain Axis

Author

Engevik, Melinda A., Luck, Berkley, Visuthranukul, Chonnikant, Ihekweazu, Faith D., Engevik, Amy C., Shi, Zhongcheng, Danhof, Heather A., Chang-Graham, Alexandra L., Hall, Anne, Endres, Bradley T., Haidacher, Sigmund J., Horvath, Thomas D., Haag, Anthony M., Devaraj, Sridevi, Garey, Kevin W., Britton, Robert A., Hyser, Joseph M., Shroyer, Noah F., and Versalovic, James

Published
2021
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30. RISEC: Rotational Invariant Segmentation of Elongated Cells in SEM Images with Inhomogeneous Illumination

Author

Memariani, Ali, Endres, Bradley T., Bassères, Eugénie, Garey, Kevin W., Kakadiaris, Ioannis A., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Bebis, George, editor, Boyle, Richard, editor, Parvin, Bahram, editor, Koracin, Darko, editor, Ushizima, Daniela, editor, Chai, Sek, editor, Sueda, Shinjiro, editor, Lin, Xin, editor, Lu, Aidong, editor, Thalmann, Daniel, editor, Wang, Chaoli, editor, and Xu, Panpan, editor

Published
2019
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33. Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers

Author

Jo, Jinhee, primary, Hu, Chenlin, additional, Begum, Khurshida, additional, Wang, Weiqun, additional, Le, Thanh M, additional, Agyapong, Samantha, additional, Hanson, Blake M, additional, Ayele, Hossaena, additional, Lancaster, Chris, additional, Jahangir Alam, M, additional, Gonzales-Luna, Anne J, additional, and Garey, Kevin W, additional

Published
2023
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39. 366. Association Between Gut Microbiota and Health-Related Quality of Life in Patients with Recurrent Clostridioides difficile Infection: Results from the PUNCH CD3 Clinical Trial

Author

Feuerstadt, Paul, primary, Blount, Ken, additional, Guo, Amy, additional, Yang, Min, additional, García-Horton, Viviana, additional, Fillbrunn, Mirko, additional, Tillotson, Glenn S, additional, Gao, Yipeng, additional, Dubberke, Erik R, additional, and Garey, Kevin W, additional

Published
2023
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41. S1083 Association of Microbiome Composition and Health-Related Quality of Life in Patients With Recurrent Clostridioides difficile Infection: Results From the PUNCH CD3 Phase 3, Randomized, Placebo-Controlled Clinical Trial

Author

Feuerstadt, Paul, primary, Blount, Ken, additional, Guo, Amy, additional, Yang, Min, additional, García-Horton, Viviana, additional, Fillbrunn, Mirko, additional, Tillotson, Glenn, additional, Gao, Yipeng, additional, Dubberke, Erik, additional, and Garey, Kevin W., additional

Published
2023
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42. Reply to Fabre et al

Author

McDonald, L. Clifford, Johnson, Stuart, Bakken, Johan S., Garey, Kevin W., Kelly, Ciaran, and Gerding, Dale N.

Published
2018

47. Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

Author

Jo, Jinhee, Hu, Chenlin, Begum, Khurshida, Wang, Weiqun, Le, Thanh M, Agyapong, Samantha, Hanson, Blake M, Ayele, Hossaena, Lancaster, Chris, Alam, M Jahangir, Gonzales-Luna, Anne J, and Garey, Kevin W

Subjects
GUT microbiome, CLINICAL trial registries, VANCOMYCIN, CLOSTRIDIUM diseases, CLOSTRIDIOIDES difficile, PHARMACOKINETICS
Abstract

Background Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults. Methods This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18–40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations were assessed, and microbiome changes were compared. Results Sixteen healthy volunteers with a mean age of 26 (standard deviation [SD], 5) years were enrolled; 62.5% were male, and participants' mean body mass index was 23.5 (SD, 4.0) kg/m2. Omadacycline was well tolerated with no safety signal differences between the 2 antibiotics. A rapid initial increase in fecal concentrations of omadacycline was observed compared to vancomycin, with maximum concentrations achieved within 48 hours. A significant difference in alpha diversity was observed following therapy in both the omadacycline and vancomycin groups (P <.05). Bacterial abundance and beta diversity analysis showed differing microbiome changes in subjects who received omadacycline versus vancomycin. Conclusions Subjects given omadacycline had high fecal concentrations with a distinct microbiome profile compared to vancomycin. Clinical Trials Registration NCT06030219. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Effect of Fecal Microbiota, live-jslm (RBL) on Health-Related Quality of Life in Patients with Recurrent Clostridioides difficile Infection: Results from the PUNCH CD3 Clinical Trial

Author

Garey, Kevin W, primary, Dubberke, Erik R, additional, Guo, Amy, additional, Harvey, Adam, additional, Yang, Min, additional, García-Horton, Viviana, additional, Fillbrunn, Mirko, additional, Wang, Hongjue, additional, Tillotson, Glenn S, additional, Bancke, Lindy L, additional, and Feuerstadt, Paul, additional

Published
2023
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