166 results on '"Buddy Creech"'
Search Results
152. Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response
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Karen L. Kotloff, Kathryn M. Edwards, Lisa A. Jackson, Andrea A. Berry, Edwin L. Anderson, Abbie R. Bellamy, Wendy A. Keitel, Isaac P. Thomsen, Irene Graham, James D. Campbell, C. Buddy Creech, Sharon E. Frey, Hana M. El Sahly, Robert L. Atmar, Andres F. Gutierrez, Shital M. Patel, Heather Hill, and Diana L. Noah
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Adult ,Male ,Squalene ,Influenza vaccine ,medicine.medical_treatment ,alpha-Tocopherol ,MF59 ,Polysorbates ,Antibodies, Viral ,Influenza A Virus, H7N9 Subtype ,medicine.disease_cause ,Adjuvants, Immunologic ,Double-Blind Method ,Influenza, Human ,Influenza A virus ,medicine ,Humans ,AS03 ,Hemagglutination, Viral ,business.industry ,Immunogenicity ,Age Factors ,Antibody titer ,General Medicine ,Hemagglutination Inhibition Tests ,Middle Aged ,Vaccination ,Drug Combinations ,Influenza Vaccines ,Immunology ,Female ,business ,Adjuvant - Abstract
Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines.To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations.Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64 years from September 2013 through November 2013; safety follow-up was completed in January 2015.The H7N9 vaccine was given on days 0 and 21 at nominal doses of 3.75 µg, 7.5 µg, 15 µg, and 45 µg of hemagglutinin with or without AS03 or MF59 adjuvant mixed on site.Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or higher at 21 days after the second vaccination; vaccine-related serious adverse events through 12 months after the first vaccination; and solicited signs and symptoms after vaccination through day 7.Two doses of vaccine were required to induce detectable antibody titers in most participants. After 2 doses of an H7N9 formulation containing 15 µg of hemagglutinin given without adjuvant, with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer of 40 or higher was 2% (95% CI, 0%-7%) without adjuvant (n = 94), 84% (95% CI, 76%-91%) with AS03 adjuvant (n = 96), and 57% (95% CI, 47%-68%) with MF59 adjuvant (n = 92) (P .001 for comparison of the AS03 and MF59 schedules). The 2 schedules alternating AS03-and MF59-adjuvanted formulations led to lower geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95% CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations (n = 96) (103.4 [95% CI, 78.7-135.9]; P .001) but higher GMTs than 2 doses of MF59-adjuvanted formulation (n = 94) (29.0 [95% CI, 22.4-37.6]; P .001).The AS03 and MF59 adjuvants augmented the immune responses to 2 doses of an inactivated H7N9 influenza vaccine, with AS03-adjuvanted formulations inducing the highest titers. This study of 2 adjuvants used in influenza vaccine formulations with adjuvant mixed on site provides immunogenicity information that may be informative to influenza pandemic preparedness programs.clinicaltrials.gov Identifier: NCT01942265.
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- 2015
153. Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
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Lana M. Olson, Richard H. Ho, Ben Saville, Yuki Bradford, Sara L. Van Driest, Dan M. Roden, Sarah Wilson, Josh C. Denny, Prince J. Kannankeril, Christian M. Shaffer, Jessica T. Delaney, Terrie Kitchner, Dana C. Crawford, Iftikhar J. Kullo, Neelam A. Patel, Hayan Jouni, Amy L. Potts, Murray H. Brilliant, C. Buddy Creech, Scott J. Hebbring, Erica Bowton, Digna R. Velez Edwards, Tracy L. McGregor, and Susan I. Vear
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Adult ,Male ,Nephrology ,Oncology ,medicine.medical_specialty ,Genotype ,030232 urology & nephrology ,lcsh:Medicine ,Renal function ,Locus (genetics) ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Nephrotoxicity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Vancomycin ,Internal medicine ,medicine ,Chromosomes, Human ,Humans ,lcsh:Science ,Adaptor Proteins, Signal Transducing ,Aged ,030304 developmental biology ,0303 health sciences ,Creatinine ,Multidisciplinary ,lcsh:R ,GTPase-Activating Proteins ,Middle Aged ,3. Good health ,chemistry ,Connexin 43 ,lcsh:Q ,Chromosomes, Human, Pair 6 ,Female ,Genome-Wide Association Study ,Research Article ,medicine.drug - Abstract
Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 x 10(-7)). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10(-7). Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.
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- 2015
154. 599Rapid rises in antibody titers observed following single dose administration of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) to healthy adults
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Robin Hubler, Shite Sebastian, Kathrin U. Jansen, Nanra Js, Robert W. Frenck, Annaliesa S. Anderson, Joseph M. Severs, Joseph Eiden, Edward T. Zito, James Baber, Buddy Creech C, Douglas Girgenti, Martin K. Kankam, Sheldon E, and David J. Seiden
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Gerontology ,IDWeek 2014 Abstracts ,Infectious Diseases ,Oncology ,Antigen ,Oral Abstracts ,Staphylococcus aureus ,business.industry ,Immunology ,medicine ,Antibody titer ,medicine.disease_cause ,business - Published
- 2014
155. Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study.
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JrFrenck, Robert W., Buddy Creech, C., Sheldon, Eric A., Seiden, David J., Kankam, Martin K., Baber, James, Zito, Edward, Hubler, Robin, Eiden, Joseph, Severs, Joseph M., Sebastian, Shite, Nanra, Jasdeep, Jansen, Kathrin U., Gruber, William C., Anderson, Annaliesa S., and Girgenti, Douglas
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STAPHYLOCOCCUS aureus infections , *VACCINE safety , *BACTERIAL vaccines , *BACTERIAL antigens , *PLACEBOS , *RANDOMIZED controlled trials , *PREVENTION - Abstract
Background A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag. Methods In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18–64 years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; antigen-specific immunogenicity was assessed using a four-plex competitive Luminex® immunoassay (cLIA). Results A high proportion of SA4Ag recipients met the pre-defined antibody thresholds for each antigen at Day 29. A substantial and dose-level dependent immune response was observed for rP305A, with up to 18-fold rises in cLIA titres at Day 29. Robust functional responses were demonstrated, with >80-fold and >20-fold rises in OPA assay titres at Day 29 using S. aureus strains expressing capsular polysaccharide serotypes 5 and 8, respectively. Durable antibody responses were observed through month 12, gradually waning from peak levels achieved by days 11–15. SA4Ag was well tolerated, and no vaccine-related serious adverse events were reported. Conclusions Single-dose vaccination of SA4Ag in healthy adults aged 18–64 years safely induced rapid and robust functional immune responses that were durable through month 12, supporting further development of this vaccine. Trial registration number: NCT01364571 [ABSTRACT FROM AUTHOR]
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- 2017
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156. 599Rapid rises in antibody titers observed following single dose administration of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) to healthy adults
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Frenck, Robert W., primary, Buddy Creech, C., additional, Sheldon, Eric, additional, Seiden, David, additional, Kankam, Martin K., additional, Baber, James, additional, Zito, Edward T., additional, Hubler, Robin, additional, Eiden, Joseph, additional, Severs, Joseph M., additional, Sebastian, Shite, additional, Nanra, Jasdeep S., additional, Jansen, Kathrin, additional, Anderson, Annaliesa S., additional, and Girgenti, Douglas, additional
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- 2014
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157. 298Association between Contact Sports and Colonization with Methicillin-Resistant Staphylococcus aureus in a Prospective Cohort of Collegiate Athletes
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Jimenez-Truque, Natalia, primary, Saye, Elizabeth, additional, Soper, Nicole, additional, Saville, Ben, additional, Thomsen, Isaac, additional, Edwards, Kathryn, additional, and Buddy Creech, C., additional
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- 2014
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158. Practice Patterns of Providers for the Management of Staphylococcus aureus Bacteremia in Children: Results of an Emerging Infections Network Survey.
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Wood, James B, Fricker, Gregory P, Beekmann, Susan E, Polgreen, Philip, and Buddy Creech, C
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We conducted a survey of pediatric infectious diseases providers in the Emerging Infections Network regarding the workup and treatment of children with Staphylococcus aureus bacteremia (SAB). We found significant practice variation in the management of children with SAB. These findings emphasize the need for further research to guide best practices.
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- 2018
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159. Immunogenicity of Avian Influenza A/Anhui/01/2005(H5N1) Vaccine With MF59 Adjuvant
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Heather Hill, Robert B. Belshe, Srilatha Edupuganti, Patricia L. Winokur, Rowena J. Dolor, Christopher W. Woods, Irene Graham, Wilbur H. Chen, Emmanuel B. Walter, Mark J. Mulligan, Sharon E. Frey, C. Buddy Creech, Abbie R. Bellamy, Lisa A. Jackson, Kathryn M. Edwards, Edwin L. Anderson, Nadine Rouphael, Christine B. Turley, and Paul Spearman
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medicine.medical_specialty ,H5N1 vaccine ,business.industry ,Immunogenicity ,medicine.medical_treatment ,MF59 ,General Medicine ,medicine.disease_cause ,Influenza A virus subtype H5N1 ,Vaccination ,Internal medicine ,Immunology ,medicine ,Influenza A virus ,Adverse effect ,business ,Adjuvant - Abstract
Importance The need to respond quickly to potential influenza pandemics is important. Immunologic priming (initial presentation of an antigen to allow antibody responses on revaccination) with vaccine directed toward an older avian influenza H5 strain might lead to secondary antibody responses to a single dose of more current H5 avian influenza vaccine. Objectives To assess priming with the older avian influenza A/Vietnam/1203/2004(H5N1) (Vietnam) vaccine and to conduct dose-response studies with vaccine directed against the more contemporary H5N1 avian influenza virus, influenza A/Anhui/01/2005 (Anhui). Design, Setting, and Participants Multicenter US randomized clinical trial beginning in June 2010 with follow-up continuing through October 2011 enrolling 72 healthy adults who were vaccinated 19 to 25 months previously with the Vietnam vaccine and 565 vaccine-naive adults. Interventions Participants who were previously vaccinated with 90 µg of unadjuvanted Vietnam vaccine were randomly assigned to receive 3.75 µg of avian influenza Anhui vaccine with or without MF59 adjuvant, stratified by 1 vs 2 previous doses (1 dose: n = 18 with MF59 and n = 17 without; 2 doses: n = 19 with MF59 and n = 18 without). Vaccine-naive individuals were randomly assigned to receive Ahnui vaccine with or without MF59 adjuvant in 1 of 5 doses (3.75 µg [n = 55 with MF59 and n = 59 without], 7.5 µg [n = 51 with MF59 and n = 57 without], 15 µg [n = 48 with MF59 and n = 44 without], 45 µg [n = 47 with MF59 and n = 47 without], or 90 µg [n = 57 without adjuvant]) or placebo (n = 100) given at days 0 and 28. Main Outcomes and Measures The primary immunogenicity outcome was hemagglutination inhibition assay (HAI) titer against each vaccine antigen 1 month (day 28) and 6 months (day 180) after last vaccination. The primary safety outcomes were local and systemic adverse events on days 0 to 7 after each vaccination and serious adverse events. Results Previously vaccinated participants manifested secondary antibody responses after receipt of low-dose Anhui vaccine (“boosting”); by day 28, 21% to 50% developed HAI responses of 1:40 or greater. Use of adjuvant was not associated with increased HAI responses. Among vaccine-naive participants (n = 565), the optimum dose was 7.5 µg of antigen with adjuvant (geometric mean titer [GMT], 63.3; 95% CI, 43.0-93.1). The greatest response to unadjuvanted antigen was seen at the highest dose, 90 µg (GMT, 28.5; 95% CI, 19.7-41.2). Local or systemic reactions occurred, respectively, in 40 (78%) and 25 (49%) of 51 participants who received 7.5 µg plus adjuvant vs 50 (88%) and 29 (51%) of 57 who received 90 µg of unadjuvanted vaccine. In general, antibodies were short-lived, and by day 180, HAI titers had decreased to less than 1:20 in all treatment groups. Conclusions and Relevance Previous receipt of a single dose of influenza A(H5N1) Vietnam vaccine was associated with sufficient immunologic priming to facilitate antibody response to a different H5N1 antigen using low-dose Anhui (booster) vaccine. In participants who had not previously received H5 vaccine, low-dose Anhui vaccine plus adjuvant was more immunogenic compared with higher doses of unadjuvanted vaccine. Trial Registration clinicaltrials.gov Identifier:NCT00680069
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- 2014
160. 298Association between Contact Sports and Colonization with Methicillin-Resistant Staphylococcus aureus in a Prospective Cohort of Collegiate Athletes
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C. Buddy Creech, Elizabeth J. Saye, Ben Saville, Nicole Soper, Natalia Jimenez-Truque, Kathryn M. Edwards, and Isaac P. Thomsen
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medicine.medical_specialty ,biology ,business.industry ,Athletes ,medicine.disease_cause ,biology.organism_classification ,Methicillin-resistant Staphylococcus aureus ,Microbiology ,Infectious Diseases ,Oncology ,Internal medicine ,medicine ,Microbial colonization ,Colonization ,Prospective cohort study ,business - Published
- 2014
161. Systems biology assessment of human immune responses after seasonal trivalent inactivated influenza vaccine (P4307)
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Kristen Hoek, Leigh Howard, Tara Allos, Parimal Samir, Xinnan Niu, Buddy Creech, Kathryn Edwards, and Andrew Link
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Immunology ,Immunology and Allergy - Abstract
Systems biology represents a novel approach to comprehensively study the human immune response to vaccines at the global transcriptional and proteomic level. However, most systems vaccinology approaches utilize total PBMCs in their analyses. In this context, responses of underrepresented immune cell types in the blood are potentially obscured by the predominant cells in the PBMC fraction, and the contribution of PMNs is completely ignored. To investigate the contribution of individual cell types in the immune response following vaccination, we developed a rapid and efficient method for purifying large numbers of T cells, B cells, monocytes, NK cells, myeloid DCs and neutrophils from fresh venous human blood for systems vaccinology studies. This optimized protocol was applied to adult volunteers vaccinated with 2011-12 seasonal TIV. 100mL blood was obtained prior to and on days 1, 3, and 7 post-vaccination. Whole blood, PBMC and PMN fractions were subjected to phenotypic analysis by flow cytometry. Immune cells were fractionated and processed for RNA and protein extraction in a single day. RNA-Seq and quantitative proteomics were performed on purified cells in order to determine individual expression profiles. Our results show significant variation in the phenotypes and expression profiles of immune cells at each time point. This innovative systems approach is currently being utilized to evaluate vaccine safety and efficacy in an adjuvanted influenza clinical trial.
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- 2013
162. Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus among skin and soft tissue infections in an emergency department in Guyana.
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Dozois, Adeline, Thomsen, Isaac, Jimenez-Truque, Natalia, Soper, Nicole, Pearson, Alexis, Mohamed-Rambaran, Pheona, Dettorre, Kristen B., Buddy Creech, C., Wright, Seth W., and Creech, C Buddy
- Abstract
Objective: The characteristics of staphylococcal skin and soft tissue infections (SSTIs) are poorly understood in northern South America and the Caribbean. The objectives of this study were to determine the frequency of methicillin resistance among Staphylococcus aureus isolates in an emergency department (ED) in Guyana and to identify specific molecular characteristics of these methicillin-resistant Staphylococcus aureus (MRSA) strains.Methods: This was a cross-sectional study conducted at the main teaching hospital in Georgetown, Guyana. Eligible subjects included patients of all ages with SSTIs with obtainable purulent material. Purulent material was cultured, and S. aureus isolates were evaluated for antibiotic susceptibilities by disc diffusion. Molecular characterisation of MRSA isolates included identification of SCCmec type, assignment of genetic relatedness by rep-PCR and determination of the presence of two exotoxins, Panton-Valentine Leukocidin (PVL) and LukAB.Results: Eighty-five samples were collected; of these, 47 grew S. aureus. 24 of the 47 S. aureus samples were MRSA (51%; 95% CI 37% to 65%), representing 28% of all samples. All MRSA isolates were SCCmec type IV, PVL positive, LukAB positive and were highly related to the current epidemic clone in the USA, USA300.Conclusions: Here, we demonstrate a clinically significant proportion of methicillin resistance in SSTI-associated staphylococcal isolates. Guyanese isolates were highly related to the most common community-associated strain seen in the USA, USA300. These results have important implications for empiric antibiotic therapy and infection control policies in Guyana and similar settings. [ABSTRACT FROM AUTHOR]- Published
- 2015
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163. Safety of LAIV4 in Children With Asthma
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Centers for Disease Control and Prevention, Duke University, Children's Hospital Medical Center, Cincinnati, and Buddy Creech, Associate Professor of Pediatrics
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- 2021
164. Kinetics of the Immune Response to Inactivated Influenza Vaccine in Healthy Adults (KIRV)
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Human Vaccines Project and Buddy Creech, Associate Professor of Pediatrics
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- 2019
165. Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy.
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Sara L Van Driest, Tracy L McGregor, Digna R Velez Edwards, Ben R Saville, Terrie E Kitchner, Scott J Hebbring, Murray Brilliant, Hayan Jouni, Iftikhar J Kullo, C Buddy Creech, Prince J Kannankeril, Susan I Vear, Kyle B Brothers, Erica A Bowton, Christian M Shaffer, Neelam Patel, Jessica T Delaney, Yuki Bradford, Sarah Wilson, Lana M Olson, Dana C Crawford, Amy L Potts, Richard H Ho, Dan M Roden, and Josh C Denny
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Medicine ,Science - Abstract
Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 x 10(-7)). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10(-7). Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.
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- 2015
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166. Niche specialization and spread of Staphylococcus capitis involved in neonatal sepsis
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Wirth, T., Bergot, M., Rasigade, J. -P., Pichon, B., Barbier, M., Martins-Simoes, P., Jacob, L., Pike, R., Tissieres, P., Picaud, J. -C., Kearns, A., Supply, P., Butin, M., Laurent, F., Adamkova, V., Barkham, T., Becker, K., Bennett, D., Claris, O., Creech, C. B., De Lencastre, H., Deighton, M., Denis, O., Ferguson, J., Huang, Y. -C., Klingenberg, C., Ingebretsen, A., Laferriere, C., dos Santos, K. R. N., Schrenzel, J., Spiliopoulou, I., Stefani, S., Taeksoo, K., Tarkka, E., Friedrich, A., Vandenbroucke-Grauls, C., Ussher, J., Vandenesch, F., Westblade, L., Lindsay, J., Larsen, A. R., Zanger, P., Kahl, B. C., Aymerich, C. P., Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Université Paris sciences et lettres (PSL), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Public Health England [London], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital de la Croix-Rousse [CHU - HCL], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), This project was supported by the European Society of Clinical Microbiology and Infectious Diseases study group (Project P307-14), the Fondation pour la Recherche Médicale (project ING20160435683) and the European Union Patho-Ngen-Trace (project FP7-278864)., The International Consortium for Staphylococcus capitis neonatal sepsis : Vaclava Adamkova, Timothy Barkham, Karsten Becker, Desiree Bennett, olivier Claris, Clarence Buddy Creech, Herminia De Lencastre, Margaret Deighton, Olivier Denis, John Ferguson, yhu-Chering Huang, Claus Klingenberg, Andre Ingebretsen, Celine Laferrière, Katia Regina Netto dos Santos, Jacques Schrenzel, Iris Spiliopoulou, Stefania Stefani, Kim TaekSoo, Eveliina Tarkka, Alex Friedrich, Christina Vandenbroucke-Grauls, James Ussher, Francois Vandenesch and Lars Westblade, The ESGS Study Group of ESCMID : Jodi Lindsay, Francois Vandenesch, Anders Rhod Larsen, Philipp Zanger, Barbara C. Kahl and Cristina Prat Aymerich, European Project: 278864,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PATHONGEN-TRACE(2012), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Endotoxines, Structures et Réponses de l'hôte (ESHR), Département Microbiologie (Dpt Microbio), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Schrenzel, Jacques
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[SDV]Life Sciences [q-bio] ,Clone (cell biology) ,Drug resistance ,Applied Microbiology and Biotechnology ,Staphylococcus capitis ,Drug Resistance, Multiple, Bacterial/drug effects/genetics ,Drug Resistance, Multiple, Bacterial ,Clade ,Neonatal Sepsis/microbiology ,Recombination, Genetic ,Genetics ,0303 health sciences ,biology ,Neonatal sepsis ,Staphylococcal Infections ,Anti-Bacterial Agents ,3. Good health ,Staphylococcus capitis/drug effects/genetics/isolation & purification/pathogenicity ,Vancomycin/therapeutic use ,Phenotype ,Genes, Bacterial/genetics ,Vancomycin ,France ,Neonatal Sepsis ,medicine.drug ,Adult ,Microbiology (medical) ,Genotype ,Immunology ,Microbial Sensitivity Tests ,Polymorphism, Single Nucleotide ,Microbiology ,Anti-Bacterial Agents/pharmacology ,03 medical and health sciences ,Antibiotic resistance ,Intensive Care Units, Neonatal ,Intensive care ,medicine ,Humans ,030304 developmental biology ,030306 microbiology ,Infant, Newborn ,Infant ,Bayes Theorem ,Cell Biology ,biology.organism_classification ,medicine.disease ,Staphylococcal Infections/microbiology ,Genes, Bacterial ,Mutation ,Genome, Bacterial ,Genome-Wide Association Study - Abstract
International audience; The multidrug-resistant Staphylococcus capitis NRCS-A clone is responsible for sepsis in preterm infants in neonatal intensive care units (NICUs) worldwide. Here, to retrace the spread of this clone and to identify drivers of its specific success, we investigated a representative collection of 250 S. capitis isolates from adults and newborns. Bayesian analyses confirmed the spread of the NRCS-A clone and enabled us to date its emergence in the late 1960s and its expansion during the 1980s, coinciding with the establishment of NICUs and the increasing use of vancomycin in these units, respectively. This dynamic was accompanied by the acquisition of mutations in antimicrobial resistance- and bacteriocin-encoding genes. Furthermore, combined statistical tools and a genome-wide association study convergently point to vancomycin resistance as a major driver of NRCS-A success. We also identified another S. capitis subclade (alpha clade) that emerged independently, showing parallel evolution towards NICU specialization and non-susceptibility to vancomycin, indicating convergent evolution in NICU-associated pathogens. These findings illustrate how the broad use of antibiotics can repeatedly lead initially commensal drug-susceptible bacteria to evolve into multidrug-resistant clones that are able to successfully spread worldwide and become pathogenic for highly vulnerable patients.
- Published
- 2020
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