15 results on '"den Reijer, M."'
Search Results
2. Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis
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Geersing, T. H., Franssen, E. J.F., Spronk, P. E., van Kan, H. J.M., den Reijer, M., van der Voort, P. H.J., and Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
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Pharmacology ,Microbiology (medical) ,Infectious Diseases ,Amphotericin B ,Critical Illness ,Sepsis ,Humans ,Intraabdominal Infections ,Pharmacology (medical) ,Renal Insufficiency ,Propensity Score ,Communicable Diseases ,Retrospective Studies - Published
- 2022
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3. Hepatitis C Elimination in the Netherlands (CELINE): How nationwide retrieval of lost to follow-up hepatitis C patients contributes to micro-elimination
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Isfordink, Cas J., primary, van Dijk, Marleen, additional, Brakenhoff, Sylvia M., additional, Kracht, Patricia A.M., additional, Arends, Joop E., additional, de Knegt, Robert J., additional, van der Valk, Marc, additional, Drenth, Joost P.H., additional, van den Berg, M., additional, Honkoop, P., additional, Abraham, S., additional, Bosman, S., additional, van Wijngaarden, P., additional, Steenhuisen, K., additional, Friederich, P., additional, Dofferhoff, A.S. M., additional, Berkhout, J., additional, ter Borg, F., additional, da Silva, J.M., additional, Verhagen, M.A.M.T., additional, Vos, X., additional, Vlaar, K., additional, Douma, R., additional, Erkelen, W.G., additional, den Reijer, M., additional, Hoebe, C.J.P.A., additional, Heil, J., additional, Baven, M., additional, van Soest, H., additional, Korkmaz, K. Sebib, additional, Bezemer, G., additional, Lammers, A.J.J., additional, Debast, S.B., additional, de Jong, H.J.M., additional, Bus, P., additional, Sturm, P., additional, den Hollander, J., additional, Kampschreur, L.M., additional, Venneman, N., additional, Bosma, F., additional, Koc, O.M., additional, Ackens, R., additional, van Oorschot, E., additional, Klemt-Kropp, M., additional, Baak, L.C., additional, Brouwer, J.T., additional, Spanier, B.W.M., additional, Swanink, C., additional, Blokzijl, H., additional, Knoester, M., additional, Liedorp, P., additional, van Bergeijk, J., additional, and van Nunen, A., additional
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- 2022
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4. A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing bla VIM-1 and mcr-9 in the Netherlands
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Hendrickx, Antoni P. A., Debast, Sylvia, Pérez-Vázquez, María, Schoffelen, Annelot F., Notermans, Daan W., Landman, Fabian, Wielders, Cornelia C. H., Cañada Garcia, Javier E., Flipse, Jacky, de Haan, Angela, Witteveen, Sandra, van Santen-Verheuvel, Marga, de Greeff, Sabine C., Kuijper, Ed, Schouls, Leo M., Maijer-Reuwer, A., Leversteijn-van Hall, M. A., Kluytmans, J. A. J. W., Spijkerman, I. J. B., van Dijk, K., Halaby, T., Zwart, B., Diederen, B. M. W., Voss, A., Dorigo-Zetsma, J. W., Ott, A., Oudbier, J. H., van der Vusse, M., Vlek, A. L. M., Buiting, A. G. M., Bode, L., Paltansing, S., van Griethuysen, A. J., den Reijer, M., van Trijp, M., van Elzakker, E. P. M., Muller, A. E., van der Linden, M. P. M., van Rijn, M., Wolfhagen, M. J. H. M., Waar, K., Kolwijck, E., Silvis, W., Schulin, T., Damen, M., Dinant, S., van Mens, S. P., Melles, D. C., Cohen Stuart, J. W. T., van Ogtrop, M. L., Overdevest, I. T. M. A., van Dam, A. P., Wertheim, H., Frénay, H. M. E., Sinnige, J. C., Mattsson, E. E., Bosboom, R. W., Stam, A., de Jong, E., Roescher, N., Heikens, E., Steingrover, R., Troelstra, A., Bathoorn, E., Trienekens, T. A. M., van Dam, D. W., de Brauwer, E. I. G. B., Stals, F. S., Government of Netherlands, Medical Microbiology and Infection Prevention, AII - Inflammatory diseases, Elderly care medicine, APH - Aging & Later Life, AII - Infectious diseases, Nursing, APH - Health Behaviors & Chronic Diseases, and Experimental Immunology
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0301 basic medicine ,Carbapenem ,biology ,Brief Report ,030106 microbiology ,Broth microdilution ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,bacterial infections and mycoses ,Meropenem ,Microbiology ,03 medical and health sciences ,030104 developmental biology ,Plasmid ,AcademicSubjects/MED00290 ,Colistin ,medicine ,Multilocus sequence typing ,AcademicSubjects/MED00740 ,AcademicSubjects/MED00230 ,Enterobacter cloacae ,Etest ,medicine.drug - Abstract
Background Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. Objectives To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015–20 in the Netherlands. Methods Short- and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. Results pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by Conclusions The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the blaVIM-1 carbapenemase and the mcr-9 colistin resistance gene.
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- 2021
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5. Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching
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Geersing, T H, primary, Franssen, E J F, additional, Spronk, P E, additional, van Kan, H J M, additional, den Reijer, M, additional, and van der Voort, P H J, additional
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- 2021
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6. Plasmid diversity among genetically related Klebsiella pneumoniae bla KPC-2 and bla KPC-3 isolates collected in the Dutch national surveillance
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Hendrickx, APA, Landman, F, de Haan, A, Borst, D, Witteveen, S, van Santen-Verheuvel, MG, van der Heide, HGJ, Schouls, LM, Halaby, T, Steingrover, R, Stuart, JWTC, Melles, DC, Dijk, K, Spijkerman, IJB, Notermans, DW, Oudbier, JH, van Ogtrop, ML, Dam, A, den Reijer, M, Kluytmans, JAJW, van der Linden, MPG, Mattsson, EE, van der Vusse, M, Jong, EM, Maijer-Reuwer, A, van Trijp, M, van Griethuysen, AJ, Ott, A, Bathoorn, E, Sinnige, JC, Heikens, E, de Brauwer, EIGB, Stals, FS, Silvis, W, Dorigo-Zetsma, JW, Waar, K, van Mens, SP, Roescher, N, Voss, A, Wertheim, HFL, Slingerland, BCGC, Frenay, HME, Schulin, T, Diederen, BMW, Bode, Lonneke, Rijn, M, Dinant, S, Damen, M, de Man, P, Leversteijn-van Hall, MA, van Elzakker, EP, Muller, AE, Schneeberger, P, van Dam, DW, Buiting, AG, Vlek, ALM, Stam, A, Troelstra, A, Overdevest, ITMA, Bosboom, RW, Trienekens, TAM, Wolfhagen, MJ, Paltansing, S, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Surgery, Medical Microbiology & Infectious Diseases, Experimental Immunology, Nursing, APH - Aging & Later Life, and APH - Health Behaviors & Chronic Diseases
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0301 basic medicine ,DNA, Bacterial ,Klebsiella pneumoniae ,030106 microbiology ,lcsh:Medicine ,Virulence ,Biology ,Microbiology ,Article ,beta-Lactamases ,03 medical and health sciences ,Plasmid ,polycyclic compounds ,Humans ,Insertion sequence ,lcsh:Science ,Pathogen ,Netherlands ,Genetics ,Multidisciplinary ,Strain (biology) ,lcsh:R ,High-Throughput Nucleotide Sequencing ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Resistome ,Computational biology and bioinformatics ,Klebsiella Infections ,030104 developmental biology ,lcsh:Q ,Plasmidome ,Cation transport - Abstract
Carbapenemase-producingKlebsiella pneumoniaeemerged over the past decades as an important pathogen causing morbidity and mortality in hospitalized patients. For infection prevention and control, it is important to track the spread of bacterial strains in humans including the plasmids they contain. However, little is known concerning the plasmid repertoire amongK. pneumoniaestrains. Therefore, the major aim was to recapitulate the size, contents and diversity of the plasmids of genetically relatedK. pneumoniaestrains harboring the beta-lactamase geneblaKPC-2orblaKPC-3to determine their dissemination in the Netherlands and the former Dutch Caribbean islands from 2014-2019. Next-generation sequencing was combined with long-read third-generation sequencing to reconstruct 18 plasmids ofK. pneumoniae. wgMLST revealed five genetic clusters (termed KpnClusters) comprised ofK. pneumoniae blaKPC-2isolates and four clusters consisted ofblaKPC-3isolates. Each cluster was characterized by a distinct resistome and plasmidome. KpnCluster-019blaKPC-2isolates were found both in the Netherlands and the Caribbean islands.K. pneumoniae blaKPC-3isolates were found in the collection of the Netherlands. The 18 plasmids were mostly unrelated and varied betweenK. pneumoniae blaKPC-2andblaKPC-3clusters. However, the large and medium sized plasmids contained a variety of antibiotic resistance genes, transposons, insertion sequence elements, conjugal transfer systems, cation transport systems, toxin/antitoxin systems, and prophage-related sequence elements. The small plasmids carried genes implicated in virulence. Thus, implementing long-read plasmid sequencing analysis forK. pneumoniaesurveillance provided important insights in the success and understanding of transmission of a KpnCluster-019blaKPC-2strain between the Netherlands and the Caribbean.ImportanceCarbapenemase-producingKlebsiella pneumoniaehas spread globally and is of great concern for debilitated patients.K.pneumoniaeis notorious for spreading antimicrobial resistance genes by plasmids amongEnterobacterales. Combining short and long read sequencing enables reconstruction of plasmids containing antibiotic resistance genes, conjugation machinery, transposons, toxins and/or virulence determinants and thereby enhancing international pathogen surveillance.
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- 2020
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7. Plasmid diversity among genetically related Klebsiella pneumoniae bla KPC-2 and bla KPC-3 isolates collected in the Dutch national surveillance
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Hendrickx, A.P.A. (Antoni), Landman, F., Haan, A. (Alexander) de, Borst, D., Witteveen, S., Santen-Verheuvel, M. (Marga) van, van der Heide, H.G.J., Schouls, L.M., Halaby, T, Steingrover, R. (Radjin), Stuart, JWTC, Melles, D.C. (Damian), Dijk, K. (Korine) van, Spijkerman, I.J.B., Notermans, D.W. (Daan), Oudbier, J.H., van Ogtrop, M.L., van Dam, A., den Reijer, M., Kluytmans, JAJW, van der Linden, MPG, Mattsson, E.E., van der Vusse, M., Jong, E. (Eefje), Maijer-Reuwer, A., van Trijp, M., van Griethuysen, A.J., Ott, A. (Alewijn), Bathoorn, E., Sinnige, J.C., Heikens, E., Brauwer, E.I.G.B. (E. I G B) de, Stals, F.S. (Frans), Silvis, W., Dorigo-Zetsma, J.W., Waar, K., van Mens, S.P., Roescher, N., Voss, A. (Andreas), Wertheim, H.F.L. (Heiman), Slingerland, B.C.G.C. (Bibi), Frenay, H.M.E., Schülin, T. (Tanja), Diederen, BMW, Bode, L.G.M. (Lonneke), van Rijn, M., Dinant, S., Damen, M. (Mark), de Man, P., Leversteijn-van Hall, M.A., Elzakker, E. van, Muller, A.E., Schneeberger, P., van Dam, D.W., Buiting, AG, Vlek, ALM, Stam, A., Troelstra, A. (Annet), Overdevest, I.T.M.A., Bosboom, R.W., Trienekens, T.A.M., Wolfhagen, M.J., Paltansing, S, Hendrickx, A.P.A. (Antoni), Landman, F., Haan, A. (Alexander) de, Borst, D., Witteveen, S., Santen-Verheuvel, M. (Marga) van, van der Heide, H.G.J., Schouls, L.M., Halaby, T, Steingrover, R. (Radjin), Stuart, JWTC, Melles, D.C. (Damian), Dijk, K. (Korine) van, Spijkerman, I.J.B., Notermans, D.W. (Daan), Oudbier, J.H., van Ogtrop, M.L., van Dam, A., den Reijer, M., Kluytmans, JAJW, van der Linden, MPG, Mattsson, E.E., van der Vusse, M., Jong, E. (Eefje), Maijer-Reuwer, A., van Trijp, M., van Griethuysen, A.J., Ott, A. (Alewijn), Bathoorn, E., Sinnige, J.C., Heikens, E., Brauwer, E.I.G.B. (E. I G B) de, Stals, F.S. (Frans), Silvis, W., Dorigo-Zetsma, J.W., Waar, K., van Mens, S.P., Roescher, N., Voss, A. (Andreas), Wertheim, H.F.L. (Heiman), Slingerland, B.C.G.C. (Bibi), Frenay, H.M.E., Schülin, T. (Tanja), Diederen, BMW, Bode, L.G.M. (Lonneke), van Rijn, M., Dinant, S., Damen, M. (Mark), de Man, P., Leversteijn-van Hall, M.A., Elzakker, E. van, Muller, A.E., Schneeberger, P., van Dam, D.W., Buiting, AG, Vlek, ALM, Stam, A., Troelstra, A. (Annet), Overdevest, I.T.M.A., Bosboom, R.W., Trienekens, T.A.M., Wolfhagen, M.J., and Paltansing, S
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- 2020
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8. Staphylococcus aureus pathogenicity in cystic fibrosis patients-results from an observational prospective multicenter study concerning virulence genes, phylogeny, and gene plasticity
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Lange, J. (Jonas), Heidenreich, K. (Kathrin), Higelin, K. (Katharina), Dyck, K. (Kristina), Marx, V. (Vanessa), Reichel, C. (Christian), Wamel, W.J.B. (Willem) van, Den Reijer, M. (Martijn), Görlich, D. (Dennis), Kahl, B.C. (Barbara C.), Lange, J. (Jonas), Heidenreich, K. (Kathrin), Higelin, K. (Katharina), Dyck, K. (Kristina), Marx, V. (Vanessa), Reichel, C. (Christian), Wamel, W.J.B. (Willem) van, Den Reijer, M. (Martijn), Görlich, D. (Dennis), and Kahl, B.C. (Barbara C.)
- Abstract
Staphylococcus aureus and cystic fibrosis (CF) are closely interlinked. To date, however, the impact of S. aureus culture in CF airways on lung function and disease progression has only been elucidated to a limited degree. This analysis aims to identify bacterial factors associated to clinical deterioration. Data were collected during an observational prospective multi-center study following 195 patients from 17 centers. The average follow-up time was 80 weeks. S. aureus isolates (n = 3180) were scanned for the presence of 25 virulence genes and agr-types using single and multiplex PCR. The presence of specific virulence genes was not associated to clinical deterioration. For the agr-types 1 and 4, however, a link to the subjects' clinical status became evident. Furthermore, a significant longitudinal decrease in the virulence gene quantity was observed. Analyses of the plasticity of the virulence genes revealed significantly increased plasticity rates in the presence of environmental stress. The results suggest that the phylogenetic background defines S. aureus pathogenicity rather than specific virulence genes. The longitudinal loss of virulence genes most likely reflects the adaptation process directed towards a persistent and colonizing rather than infecting lifestyle.
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- 2020
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9. Plasmid diversity among genetically related Klebsiella pneumoniae blaKPC-2 and blaKPC-3 isolates collected in the Dutch national surveillance.
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Hendrickx, Antoni P. A., Landman, Fabian, de Haan, Angela, Borst, Dyogo, Witteveen, Sandra, van Santen-Verheuvel, Marga G., van der Heide, Han G. J., Schouls, Leo M., The Dutch CPE surveillance Study Group, Halaby, T., Steingrover, R., Cohen Stuart, J. W. T., Melles, D. C., van Dijk, K., Spijkerman, I. J. B., Notermans, D. W., Oudbier, J. H., van Ogtrop, M. L., van Dam, A., and den Reijer, M.
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CARBAPENEMASE ,KLEBSIELLA pneumoniae ,BETA-lactamase inhibitors ,PLASMIDS - Abstract
Carbapenemase-producing Klebsiella pneumoniae emerged as a nosocomial pathogen causing morbidity and mortality in patients. For infection prevention it is important to track the spread of K. pneumoniae and its plasmids between patients. Therefore, the major aim was to recapitulate the contents and diversity of the plasmids of genetically related K. pneumoniae strains harboring the beta-lactamase gene bla
KPC-2 or blaKPC-3 to determine their dissemination in the Netherlands and the former Dutch Caribbean islands from 2014 to 2019. Next-generation sequencing was combined with long-read third-generation sequencing to reconstruct 22 plasmids. wgMLST revealed five genetic clusters comprised of K. pneumoniae blaKPC-2 isolates and four clusters consisted of blaKPC-3 isolates. KpnCluster-019 blaKPC-2 isolates were found both in the Netherlands and the Caribbean islands, while blaKPC-3 cluster isolates only in the Netherlands. Each K. pneumoniae blaKPC-2 or blaKPC-3 cluster was characterized by a distinct resistome and plasmidome. However, the large and medium plasmids contained a variety of antibiotic resistance genes, conjugation machinery, cation transport systems, transposons, toxin/antitoxins, insertion sequences and prophage-related elements. The small plasmids carried genes implicated in virulence. Thus, implementing long-read plasmid sequencing analysis for K. pneumoniae surveillance provided important insights in the transmission of a KpnCluster-019 blaKPC-2 strain between the Netherlands and the Caribbean. [ABSTRACT FROM AUTHOR]- Published
- 2020
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10. De continue vergisting van suikers tot ethanol door Pichia Stipitis
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Philippi, M. and Den Reijer, M.
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Document uit de collectie Chemische Technologie
- Published
- 1985
11. De continue vergisting van suikers tot ethanol door Pichia Stipitis
- Author
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Philippi, M. (author), Den Reijer, M. (author), Philippi, M. (author), and Den Reijer, M. (author)
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Document uit de collectie Chemische Technologie, DelftChemTech, Applied Sciences
- Published
- 1985
12. [Persistent dermatomycosis due toTrichophyton indotineae].
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Buil JB, Meijer EFJ, den Reijer M, Zeeuwen-Franssen MEJ, Melchers WJG, and Verweij PE
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- Humans, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Tinea diagnosis, Tinea drug therapy, Tinea microbiology, Trichophyton isolation & purification, Trichophyton drug effects
- Abstract
Trichophyton indotineae is a recently identified dermatophyte that frequently causes extensive and persistent dermatomycosis, particularly tinea corporis, tinea cruris, and tinea faciei. The infection is frequently encountered in countries of the Indian subcontinent and surrounding areas. In Europe, T. indotineae has mainly been detected in patients with an epidemiological link to the aforementioned regions. Unlike dermatomycoses caused by other dermatophyte species, infections caused by T. indotineae often exhibit treatment failure with commonly prescribed antifungal drugs. Reduced susceptibility to terbinafine is often observed in T. indotineae . In addition, reduced susceptibility to itraconazole has also been reported. Due to the extensive and persistent nature of the infection, as well as the reduced susceptibility to antifungal drugs, international experts recommend aggressive treatment of T. indotineae using a combination of oral and topical antifungals. Susceptibility testing may be warranted to guide treatment decisions. Early recognition of T. indotineae infections is crucial to prevent prolonged recurrences.
- Published
- 2024
13. Diagnostic performances of four commercially available assays for the identification of SARS-CoV-2, influenza type A/B virus and RSV.
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Houwen C, van Lisdonk N, Bolier J, van Eekeren M, van Gaalen M, van Herk A, Paula Z, Peters N, den Reijer M, Mertens K, and Thai KTD
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- Humans, SARS-CoV-2 genetics, RNA, Viral genetics, Sensitivity and Specificity, Nasopharynx, COVID-19 Testing, COVID-19 diagnosis, Herpesvirus 1, Cercopithecine genetics, Influenza, Human diagnosis, Influenza A virus genetics
- Abstract
We evaluated the diagnostic performance of 4 commercially NAAT for detecting SARS-CoV-2 RNA, Influenza type A/B virus and RSV. Included tests were the Allplex™ SARS-CoV-2 fast PCR Assay (RNA extraction-free), Allplex™ RV Master Assay, Allplex™ SARS-CoV-2 fast MDx Assay (LAMP) and Aptima™ SARS-CoV-2/Flu Assay (RT-TMA). The assays' performance characteristics were determined using nasopharyngeal swabs from 270 patients with suspected SARS-CoV-2 infection. A total of 215 SARS-CoV-2 positive, 55 negative nasopharyngeal swabs and 19 bacteria strains were included. The sensitivities and specificities for detecting SARS-CoV-2, Influenza type A virus and RSV ranged between 81.8% and 100% with extremely good agreements (κ ≥ 86.8 %). The Aptima™ SARS-CoV-2/Flu Assay introduced a new result parameter, that is, TTime. Here, we showed that TTime may be used as a surrogate for Ct-value. We concluded that all assays assessed in this study can be used for routine detection of SARS-CoV-2, Influenza type A virus and RSV., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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14. Rapid detection of dermatophytes using the Seegene Novaplex™ dermatophyte assay.
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van Herk A, Houwen C, den Reijer M, Beek MN, Niehuis MJ, van Lisdonk N, Mertens K, and Thai KTD
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- Humans, Polymerase Chain Reaction, Sensitivity and Specificity, DNA, Fungal, Skin microbiology, Candida albicans, Arthrodermataceae genetics
- Abstract
Objectives: We assessed the performance of the Seegene Novaplex™ Dermatophyte Assay for diagnosis of dermatophytosis., Methods: Sixty-one clinical samples from skin, nail, hair and culture were selected based on RT-PCR according to Wisselink et al. Of these samples, 26 samples were negative and 35 samples were positive with 39 dermatophytes strains. Emerging fungal strains harbouring terbinafine resistance (i.e. T. indotineae and T. mentagrophytes) were included., Results: The specificities of the Novaplex™ Dermatophyte Assay ranged between 94.3% and 97.9%. The sensitivities for the detection of T. rubrum complex, T. mentagrophytes/T. interdigitale species complex and C. albicans were 94.1% (95% CI: 71.3-99.9), 78.6% (95% CI: 49.2-95.3) and 100% (95% CI: 69.2-100), respectively, with Cohen's kappa of at least 72.9%., Conclusions: The Seegene Novaplex™ Dermatophyte Assay can be used for reliable screening of dermatophytes, including emerging strains in a routine laboratory setting., (© 2023 Wiley-VCH GmbH.)
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- 2023
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15. Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus.
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Junge S, Görlich D, den Reijer M, Wiedemann B, Tümmler B, Ellemunter H, Dübbers A, Küster P, Ballmann M, Koerner-Rettberg C, Große-Onnebrink J, Heuer E, Sextro W, Mainz JG, Hammermann J, Riethmüller J, Graepler-Mainka U, Staab D, Wollschläger B, Szczepanski R, Schuster A, Tegtmeyer FK, Sutharsan S, Wald A, Nofer JR, van Wamel W, Becker K, Peters G, and Kahl BC
- Subjects
- Adolescent, Adult, Antibodies, Bacterial immunology, Bacterial Load, Child, Coinfection, Cystic Fibrosis diagnosis, Disease Progression, Female, Forced Expiratory Volume, Humans, Immunoglobulin G immunology, Interleukin-6 metabolism, Male, Nasal Mucosa microbiology, Prospective Studies, Respiratory Function Tests, Sputum microbiology, Staphylococcal Infections drug therapy, Young Adult, Cystic Fibrosis complications, Cystic Fibrosis physiopathology, Staphylococcal Infections etiology, Staphylococcal Infections physiopathology, Staphylococcus aureus drug effects, Staphylococcus aureus immunology
- Abstract
Background: Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads., Methods: Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors., Results: 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496)., Conclusions: In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia., Trial Registration: ClinicalTrials.gov NCT00669760., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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