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1. Real-life data on antibiotic prescription and sputum culture diagnostics in acute exacerbations of COPD in primary care

Author

Bathoorn E, Groenhof F, Hendrix R, van der Molen T, Sinha B, Kerstjens HA, Friedrich AW, and Kocks JW

Subjects
COPD, exacerbation, antimicrobial stewardship, bacteria, sputum cultures, Diseases of the respiratory system, RC705-779
Abstract

Erik Bathoorn,1 Feikje Groenhof,2 Ron Hendrix,1,3 Thys van der Molen,2,4 Bhanu Sinha,1 Huib AM Kerstjens,5 Alex W Friedrich,1 Janwillem WH Kocks2,4 1Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 2Department of Primary Care, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 3Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 4Department of Medical Microbiology, Certe – Laboratory for Infectious Diseases, Groningen, the Netherlands; 5GRIAC Research Institute, Groningen, University of Groningen, University Medical Center Groningen, the Netherlands Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are generally treated with optimization of bronchodilation therapy and a course of oral corticosteroids, mostly without antibiotics. The Dutch guidelines recommend prudent use of antibiotics, with amoxicillin or doxycycline as first choice. Here we evaluate adherence to these guidelines with regard to antibiotic prescription in AECOPD in primary care and the use of sputum cultures. Methods: We retrospectively analyzed a longitudinal cohort of patients in three primary care practices in the north-eastern region of the Netherlands from 2009 to 2013 (n=36,172 subjects) participating in the Registration Network Groningen. Antibiotics prescribed for AECOPD -10/+28 days from the start date of corticosteroid courses were evaluated. In addition, we assessed regional data on the susceptibility of respiratory pathogens from COPD patients. Results: We identified 1,297 patients with COPD. Of these, 616 experienced one or more exacerbations, resulting in a total of 1,558 exacerbations, for which 1,594 antibiotic courses were prescribed. The recommended antibiotics doxycycline and amoxicillin accounted for 56% of the prescribed antibiotics overall and for 35% in subsequent antibiotic courses. The alternative choices were not based on culture results because only in 67 AECOPD events (2.9%) sputum samples were taken. Regional data including 3,638 sputum samples showed that pathogens relevant in AECOPD were detected in 19% of cultures. Conclusion: Our study shows that guidelines regarding the prescription of antibiotics are poorly followed, particularly in recurrent exacerbations. Sputum cultures were performed in a small minority of cases. Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment. Keywords: COPD, exacerbation, antimicrobial stewardship, bacteria, sputum cultures

Published
2017

2. Unsupervised Clustering of Sputum Transcriptomes Identifies Three COPD Exacerbation Endotypes With Differing Susceptibilities and Pathobiology

Author

Sarma, A., primary, Faiz, A., additional, Ditz, B., additional, Langelier, C., additional, Nerella, S., additional, Neff, N., additional, Lyden, A., additional, Caldera, S., additional, Bolourchi, S., additional, Calfee, C.S., additional, Bathoorn, E., additional, Kerstjens, H.A.M., additional, Van den Berge, M., additional, and Christenson, S., additional

Published
2023
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3. Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

Author

Cohen Stuart, J.W.T., Melles, D.C., van Dijk, K., Visser, C.E., Notermans, D.W., van Ogtrop, M.L., Werdmuller, B.F.M., van Hees, B.C., Kluytmans, J.A.J.W., van den Bijllaardt, W., Kraan, E.M., van der Linden, M.P.M., Mattsson, E.E., Sebens, F.W., de Jong, E., Frénay, H.M.E., Maraha, B., van Griethuysen, A.J., van Asselt, G.J., Demeulemeester, A., Wintermans, B.B., van Trijp, M., Ott, A., Bathoorn, E., Lokate, M., Sinnige, J.C., de Brauwer, E.I.G.B., Stals, F.S., Silvis, W., Bakker, L.J., Dorigo-Zetsma, J.W., Ridwan, B., Waar, K., Bernards, A.T., van Mens, S.P., Roescher, N., Nabuurs-Franssen, M.H., Wertheim, H., Schülin, T., Diederen, B.M.W., Bode, L., van Rijn, M., Dinant, S., Pontesilli, O., de Man, P., Leversteijn-van Hall, M.A., van Elzakker, E.P.M., Muller, A.E., Renders, N.H., van Dam, D.W., Buiting, A.G.M., Vlek, A.L.M., Reuland, A., Frakking, F.N.J., Overdevest, I.T.M.A., Bosboom, R.W., Trienekens, T.A.M., Bruins, M.J., Wolfhagen, M.J.H.M., van der Zwaluw, K., Witteveen, S., Wielders, L., van Santen, M., Landman, F., de Haan, A., Schouls, L.M., and Bosch, T.

Published
2020
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4. Unsupervised Clustering of Sputum Transcriptomes Identifies Three COPD Exacerbation Endotypes With Differing Susceptibilities and Pathobiology

Author

Sarma, A, Faiz, A, Ditz, B, Langelier, C, Nerella, S, Neff, N, Lyden, A, Caldera, S, Bolourchi, S, Calfee, CS, Bathoorn, E, Kerstjens, HAM, Van den Berge, M, Christenson, S, Sarma, A, Faiz, A, Ditz, B, Langelier, C, Nerella, S, Neff, N, Lyden, A, Caldera, S, Bolourchi, S, Calfee, CS, Bathoorn, E, Kerstjens, HAM, Van den Berge, M, and Christenson, S

Published
2023

5. Molecular characterization of MRSA collected during national surveillance between 2008 and 2019 in the Netherlands

Author

Schouls, Leo M., Witteveen, Sandra, van Santen-Verheuvel, Marga, Labdman, Fabian, de Haan, Angela, Kuijper, Ed J., van der Heide, Han, Notermans, Daan W., Bosch, Thijs, Hendrickx, Anthony P.A., van Mansfeld, R, van Maarseveen, N, de Jong, E., Vainio, S.J., Heikens, Esther, den Reijer, Martijn, Dorigo-Zetsma, J.W. (Wendelien), Troelstra, A., Bathoorn, E., de Vries, J., van Dam, D.W., de Brauwer, E.I.G.B., Steingrover, R., Schouls, Leo M., Witteveen, Sandra, van Santen-Verheuvel, Marga, Labdman, Fabian, de Haan, Angela, Kuijper, Ed J., van der Heide, Han, Notermans, Daan W., Bosch, Thijs, Hendrickx, Anthony P.A., van Mansfeld, R, van Maarseveen, N, de Jong, E., Vainio, S.J., Heikens, Esther, den Reijer, Martijn, Dorigo-Zetsma, J.W. (Wendelien), Troelstra, A., Bathoorn, E., de Vries, J., van Dam, D.W., de Brauwer, E.I.G.B., and Steingrover, R.

Abstract

Background. Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage national MRSA surveillance has been in place since 1989. To monitor possible changes in the type-distribution and emergence of resistance and virulence, MRSA isolates are molecularly characterized. Methods. All 43,321 isolates from 36,520 persons, collected 2008–2019, were typed by multiple-locus variable number tandem repeats analysis (MLVA) with simultaneous PCR detection of the mecA, mecC and lukF-PV genes, indicative for PVL. Next-generation sequencing data of 4991 isolates from 4798 persons were used for whole genome multi-locus sequence typing (wgMLST) and identification of resistance and virulence genes. Results. We show temporal change in the molecular characteristics of the MRSA population with the proportion of PVL-positive isolates increasing from 15% in 2008–2010 to 25% in 2017–2019. In livestock-associated MRSA obtained from humans, PVL-positivity increases to 6% in 2017–2019 with isolates predominantly from regions with few pig farms. wgMLST reveals the presence of 35 genogroups with distinct resistance, virulence gene profiles and specimen origin. Typing shows prolonged persistent MRSA carriage with a mean carriage period of 407 days. There is a clear spatial and a weak temporal relationship between isolates that clustered in wgMLST, indicative for regional spread of MRSA strains. Conclusions. Using molecular characterization, this exceptionally large study shows genomic changes in the MRSA population at the national level. It reveals waxing and waning of types and genogroups and an increasing proportion of PVL-positive MRSA.

Published
2023

7. Increase in invasive group A streptococcal (Streptococcus pyogenes) infections (iGAS) in young children in the Netherlands, 2022

Author

de Gier, Brechje, Marchal, Niek, de Beer-Schuurman, Ilse, te Wierik, Margreet, Hooiveld, Mariëtte, de Melker, Hester E., van Sorge, Nina M., Stuart, J. W. T. Cohen, Melles, D. C., van Dijk, K., Alzubaidy, A., Scholing, M., Kuil, S. D., Blaauw, G. J., Altorf-van der Kuil, W., Bierman, S. M., de Greeff, S. C., Groenendijk, S. R., Hertroys, R., Kuijper, E. J., Marchal, N., Monen, J. C. M., Notermans, D. W., Polman, J., van den Reek, W. J., Schneeberger-van der Linden, C., Schoffelen, A. F., Wielders, C. C. H., de Wit, B. J., Zoetigheid, R. E., van den Bijllaardt, W., Kraan, E. M., Haeseker, M. B., da Silva, J. M., de Jong, E., Maraha, B., van Griethuysen, A. J., Wintermans, B. B., van Trijp, M. J. C. A., Wong, M., Muller, A. E., Ott, A., Lokate, M., Bathoorn, E., Sinnige, J., Silvis, W., Renders, N. H., Bakker, L. J., Dorigo-Zetsma, J. W., Waar, K., van der Beek, M. T., Leversteijn-van Hall, M. A., van Mens, S. P., Schaftenaar, E., Nabuurs-Franssen, M. H., Maat, I., Diederen, B. M. W., Bode, L. G. M., Ong, D. S. Y., van Rijn, M., Dinant, S., Pontesilli, O., van Dam, D. W., de Brauwer, E. I. G. B., Bentvelsen, R. G., Buiting, A. G. M., Vlek, A. L. M., de Graaf, M., Troelstra, A., Jansz, A. R., van Meer, M. P. A., de Vries, J., Dos Santos, C. Oliveira, Rümke, Lidewij W., Vestjens, Stefan M. T., Vlaminckx, Bart J. M., Medical Microbiology and Infection Prevention, AII - Infectious diseases, APH - Global Health, APH - Methodology, APH - Quality of Care, Experimental Immunology, AII - Inflammatory diseases, APH - Aging & Later Life, and APH - Health Behaviors & Chronic Diseases

Subjects
Adult, Chickenpox, Streptococcus pyogenes, Child, Preschool, Streptococcal Infections/diagnosis, COVID-19, Humans, Netherlands/epidemiology, Child, Herpes Zoster, Pandemics
Abstract

In 2022, a sevenfold increase in the number of notifiable invasive Streptococcus pyogenes (iGAS) infections among children aged 0-5 years was observed in the Netherlands compared with pre-COVID-19 pandemic years. Of 42 cases in this age group, seven had preceding or coinciding varicella zoster infections, nine were fatal. This increase is not attributable to a specific emm type. Vigilance for clinical deterioration as iGAS sign is warranted in young children, especially those with varicella zoster infection.

Published
2023

10. A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing bla VIM-1 and mcr-9 in the Netherlands

Author

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

Subjects
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.

Published
2021
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11. The sputum transcriptome better predicts COPD exacerbations after the withdrawal of inhaled corticosteroids than sputum eosinophils

Author

Ditz, B., primary, Sarma, A., additional, Kerstjens, H.A.M., additional, Liesker, J.J.W., additional, Bathoorn, E., additional, Vonk, J.M., additional, Bernal, V., additional, Horvatovich, P., additional, Guryev, V., additional, Caldera, S., additional, Langelier, C., additional, Faiz, A., additional, Christenson, S. A., additional, and van den Berge, M., additional

Published
2021
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12. Education and training programmes for infection prevention and control professionals: mapping the current opportunities and local needs in European countries

Author

Tsioutis, C., Birgand, G., Bathoorn, E., Deptula, A., Ten Horn, L., Castro-Sanchez, E., Săndulescu, O., Widmer, A. F., Tsakris, A., Pieve, G., Tacconelli, E., Mutters, N. T., and ESRC

Subjects
Qualifications, Infection Control, Certification, 1103 Clinical Sciences, Review, L1, RT, lcsh:Infectious and parasitic diseases, Education, Europe, RA0421, 1108 Medical Microbiology, Infection prevention, Humans, Training, lcsh:RC109-216, Education, Medical, Continuing, Infection control, 0605 Microbiology
Abstract

BACKGROUND: Studies have repeatedly highlighted the need for homogenisation of training content and opportunities in infection prevention and control (IPC) across European countries. \ud \ud OBJECTIVES: To map current training opportunities for IPC professionals, define local needs and highlight differences, across 11 European countries (Cyprus, France, England, Germany, Greece, Italy, Netherlands, Poland, Romania, Spain, Switzerland). \ud \ud SOURCES: From July 2018 to February 2019, IPC experts directly involved in IPC training and education in their countries and/or internationally were invited to complete a prespecified set of questions in order to provide a detailed description of IPC training opportunities and needs in their country. \ud \ud CONCLUSIONS: IPC training among nurses and doctors varies greatly across countries, with differences in content and type of training (e.g., standardised curriculum, educational programme, clinical experience) duration, as well as in assessment and recognition/accreditation. The observed heterogeneity in IPC training between European countries can be eliminated through establishment of interdisciplinary region-wide training programmes, with common learning objectives, shared know-how and supported by national and international professional bodies.

Published
2020

13. The sputum transcriptome better predicts COPD exacerbations after the withdrawal of inhaled corticosteroids than sputum eosinophils.

Author

Ditz, B, Sarma, A, Kerstjens, HAM, Liesker, JJW, Bathoorn, E, Vonk, JM, Bernal, V, Horvatovich, P, Guryev, V, Caldera, S, Langelier, C, Faiz, A, Christenson, SA, van den Berge, M, Ditz, B, Sarma, A, Kerstjens, HAM, Liesker, JJW, Bathoorn, E, Vonk, JM, Bernal, V, Horvatovich, P, Guryev, V, Caldera, S, Langelier, C, Faiz, A, Christenson, SA, and van den Berge, M

Abstract

Introduction: Continuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions. Methods: We performed transcriptional profiling of sputum to explore the molecular biology and compared the predictive value of an unbiased gene signature versus sputum eosinophils for exacerbations after ICS withdrawal in COPD patients. RNA-sequencing data of induced sputum samples from 43 COPD patients were associated with the time to exacerbation after ICS withdrawal. Expression profiles of differentially expressed genes were summarised to create gene signatures. In addition, we built a Bayesian network model to determine coregulatory networks related to the onset of COPD exacerbations after ICS withdrawal. Results: In multivariate analyses, we identified a gene signature (LGALS12, ALOX15, CLC, IL1RL1, CD24, EMR4P) associated with the time to first exacerbation after ICS withdrawal. The addition of this gene signature to a multiple Cox regression model explained more variance of time to exacerbations compared to a model using sputum eosinophils. The gene signature correlated with sputum eosinophil as well as macrophage cell counts. The Bayesian network model identified three coregulatory gene networks as well as sex to be related to an early versus late/nonexacerbation phenotype. Conclusion: We identified a sputum gene expression signature that exhibited a higher predictive value for predicting COPD exacerbations after ICS withdrawal than sputum eosinophilia. Future studies should investigate the utility of this signature, which might enhance personalised ICS treatment in COPD patients.

Published
2021

14. Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

Author

van der Zwaluw, K., primary, Witteveen, S., additional, Wielders, L., additional, van Santen, M., additional, Landman, F., additional, de Haan, A., additional, Schouls, L.M., additional, Bosch, T., additional, Cohen Stuart, J.W.T., additional, Melles, D.C., additional, van Dijk, K., additional, Visser, C.E., additional, Notermans, D.W., additional, van Ogtrop, M.L., additional, Werdmuller, B.F.M., additional, van Hees, B.C., additional, Kluytmans, J.A.J.W., additional, van den Bijllaardt, W., additional, Kraan, E.M., additional, van der Linden, M.P.M., additional, Mattsson, E.E., additional, Sebens, F.W., additional, de Jong, E., additional, Frénay, H.M.E., additional, Maraha, B., additional, van Griethuysen, A.J., additional, van Asselt, G.J., additional, Demeulemeester, A., additional, Wintermans, B.B., additional, van Trijp, M., additional, Ott, A., additional, Bathoorn, E., additional, Lokate, M., additional, Sinnige, J.C., additional, de Brauwer, E.I.G.B., additional, Stals, F.S., additional, Silvis, W., additional, Bakker, L.J., additional, Dorigo-Zetsma, J.W., additional, Ridwan, B., additional, Waar, K., additional, Bernards, A.T., additional, van Mens, S.P., additional, Roescher, N., additional, Nabuurs-Franssen, M.H., additional, Wertheim, H., additional, Schülin, T., additional, Diederen, B.M.W., additional, Bode, L., additional, van Rijn, M., additional, Dinant, S., additional, Pontesilli, O., additional, de Man, P., additional, Leversteijn-van Hall, M.A., additional, van Elzakker, E.P.M., additional, Muller, A.E., additional, Renders, N.H., additional, van Dam, D.W., additional, Buiting, A.G.M., additional, Vlek, A.L.M., additional, Reuland, A., additional, Frakking, F.N.J., additional, Overdevest, I.T.M.A., additional, Bosboom, R.W., additional, Trienekens, T.A.M., additional, Bruins, M.J., additional, and Wolfhagen, M.J.H.M., additional

Published
2020
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16. Education and training programmes for infection prevention and control professionals: mapping the current opportunities and local needs in European countries

Author

Tsioutis, C. Birgand, G. Bathoorn, E. Deptula, A. ten Horn, L. Castro-Sánchez, E. Săndulescu, O. Widmer, A.F. Tsakris, A. Pieve, G. Tacconelli, E. Mutters, N.T.

Abstract

Background: Studies have repeatedly highlighted the need for homogenisation of training content and opportunities in infection prevention and control (IPC) across European countries. Objectives: To map current training opportunities for IPC professionals, define local needs and highlight differences, across 11 European countries (Cyprus, France, England, Germany, Greece, Italy, Netherlands, Poland, Romania, Spain, Switzerland). Sources: From July 2018 to February 2019, IPC experts directly involved in IPC training and education in their countries and/or internationally were invited to complete a prespecified set of questions in order to provide a detailed description of IPC training opportunities and needs in their country. Conclusions: IPC training among nurses and doctors varies greatly across countries, with differences in content and type of training (e.g., standardised curriculum, educational programme, clinical experience) duration, as well as in assessment and recognition/accreditation. The observed heterogeneity in IPC training between European countries can be eliminated through establishment of interdisciplinary region-wide training programmes, with common learning objectives, shared know-how and supported by national and international professional bodies. © 2020, The Author(s).

Published
2020

17. Plasmid diversity among genetically related Klebsiella pneumoniae bla KPC-2 and bla KPC-3 isolates collected in the Dutch national surveillance

Author

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

Subjects
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.

Published
2020
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18. Plasmid diversity among genetically related Klebsiella pneumoniae bla KPC-2 and bla KPC-3 isolates collected in the Dutch national surveillance

Author

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

Published
2020
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19. Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

Author

Mulder, T. (Tessa), Kluytmans-Vandenbergh, M.F.Q. (Marjolein), Vlaminckx, B.J.M. (Bart J.), Roos, D. (Daphne), Smet, A.M. (Anne Marie) de, de Vos Tot Nederveen Cappel, R. (Robert), Verheijen, P. (Paul), Brandt, A. (Alexandra), Smits, A. (Anke), Vorm, E.R. (Eric) van der, Bathoorn, E. (Erik), Etten, B. (Boudewijn) van, Veenemans, J. (Jacobien), Weersink, A. (Annemarie), Vos, M.C. (Margreet), Veer, N.E. (Nils) van 't, Nikolakopoulos, S. (Stavros), Bonten, M., Kluytmans, J.A.J.W. (Jan), Mulder, T. (Tessa), Kluytmans-Vandenbergh, M.F.Q. (Marjolein), Vlaminckx, B.J.M. (Bart J.), Roos, D. (Daphne), Smet, A.M. (Anne Marie) de, de Vos Tot Nederveen Cappel, R. (Robert), Verheijen, P. (Paul), Brandt, A. (Alexandra), Smits, A. (Anke), Vorm, E.R. (Eric) van der, Bathoorn, E. (Erik), Etten, B. (Boudewijn) van, Veenemans, J. (Jacobien), Weersink, A. (Annemarie), Vos, M.C. (Margreet), Veer, N.E. (Nils) van 't, Nikolakopoulos, S. (Stavros), Bonten, M., and Kluytmans, J.A.J.W. (Jan)

Abstract

BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. METHODS: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. RESULTS: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46). CONCLUSIONS: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. TRIAL REGISTRATION: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17.

Published
2020
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20. Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

Author

Zwaluw, K. (Kim) van der, Witteveen, S. (S.), Wielders, L. (L.), van Santen, M. (M.), Landman, F. (F.), de Haan, A. (A.), Schouls, L.M., Bosch, T. (T.), Cohen Stuart, J.W.T. (James), Melles, D.C. (Damian), Dijk, K.D. (Karin) van, Visser, C.E., Notermans, D.W. (Daan), Ogtrop, M.L. van, Werdmuller, B.F.M. (B. F.M.), Hees, B.C. (Babette) van, Kluytmans, J.A.J.W. (Jan), van den Bijllaardt, W. (Wouter), Kraan, E.M. (E. M.), van der Linden, M.P.M. (M. P.M.), Mattsson, E.E. (E. E.), Sebens, F. (Fré), de Jong, E. (E.), Frénay, H.M.E. (H. M.E.), Maraha, B. (B.), Griethuysen, A. (Arjanne) van, van Asselt, G.J. (G. J.), Demeulemeester, A. (A.), Wintermans, B.B. (B. B.), Trijp, M.J.C.A. (Marijke) van, Ott, A. (A.), Bathoorn, E. (E.), Lokate, M. (M.), Sinnige, J.C. (J. C.), Brauwer, E.I.G.B. (E. I G B) de, Stals, F.S. (Frans), Silvis, W. (W.), Bakker, L.J. (L. J.), Dorigo-Zetsma, J.W., Ridwan, B. (B.), Waar, K. (K.), Bernards, A.T. (Alexandra), van Mens, S.P. (S. P.), Roescher, N. (N.), Nabuurs-Franssen, M.H. (M. H.), Wertheim, H.F.L. (Heiman), Schülin, T. (Tanja), Diederen, B.M.W. (Bram), Bode, L.G.M. (Lonneke), van Rijn, M. (M.), Dinant, S. (S.), Pontesilli, O. (O.), Man, P. (Peter) de, Leversteijn-van Hall, M.A. (M. A.), Elzakker, E. van, Muller, A.E. (Anouk), Renders, N. (Nicole), van Dam, D.W. (D. W.), Buiting, A.G.M. (Anton), Vlek, A.L.M. (Anne L.M.), Reuland, A. (A.), Frakking, F.N.J. (Florine N.), Overdevest, I. (Ilse), Bosboom, R.W. (R. W.), Trienekens, T.A.M. (T. A.M.), Bruins, M.J. (Marjan), Wolfhagen, M.J.H.M., Zwaluw, K. (Kim) van der, Witteveen, S. (S.), Wielders, L. (L.), van Santen, M. (M.), Landman, F. (F.), de Haan, A. (A.), Schouls, L.M., Bosch, T. (T.), Cohen Stuart, J.W.T. (James), Melles, D.C. (Damian), Dijk, K.D. (Karin) van, Visser, C.E., Notermans, D.W. (Daan), Ogtrop, M.L. van, Werdmuller, B.F.M. (B. F.M.), Hees, B.C. (Babette) van, Kluytmans, J.A.J.W. (Jan), van den Bijllaardt, W. (Wouter), Kraan, E.M. (E. M.), van der Linden, M.P.M. (M. P.M.), Mattsson, E.E. (E. E.), Sebens, F. (Fré), de Jong, E. (E.), Frénay, H.M.E. (H. M.E.), Maraha, B. (B.), Griethuysen, A. (Arjanne) van, van Asselt, G.J. (G. J.), Demeulemeester, A. (A.), Wintermans, B.B. (B. B.), Trijp, M.J.C.A. (Marijke) van, Ott, A. (A.), Bathoorn, E. (E.), Lokate, M. (M.), Sinnige, J.C. (J. C.), Brauwer, E.I.G.B. (E. I G B) de, Stals, F.S. (Frans), Silvis, W. (W.), Bakker, L.J. (L. J.), Dorigo-Zetsma, J.W., Ridwan, B. (B.), Waar, K. (K.), Bernards, A.T. (Alexandra), van Mens, S.P. (S. P.), Roescher, N. (N.), Nabuurs-Franssen, M.H. (M. H.), Wertheim, H.F.L. (Heiman), Schülin, T. (Tanja), Diederen, B.M.W. (Bram), Bode, L.G.M. (Lonneke), van Rijn, M. (M.), Dinant, S. (S.), Pontesilli, O. (O.), Man, P. (Peter) de, Leversteijn-van Hall, M.A. (M. A.), Elzakker, E. van, Muller, A.E. (Anouk), Renders, N. (Nicole), van Dam, D.W. (D. W.), Buiting, A.G.M. (Anton), Vlek, A.L.M. (Anne L.M.), Reuland, A. (A.), Frakking, F.N.J. (Florine N.), Overdevest, I. (Ilse), Bosboom, R.W. (R. W.), Trienekens, T.A.M. (T. A.M.), Bruins, M.J. (Marjan), and Wolfhagen, M.J.H.M.

Abstract

Objectives: Carbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system. Methods: Meropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS). Results: In total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n = 388, 43%), Escherichia coli (n = 264, 30%) and Enterobacter cloacae complex (n = 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with blaOXA-48 being predominant (38%, 336/892), followed by blaNDM-1 (16%, 145/892). For the first time in the Netherlands, blaOXA-181, blaOXA-232 and blaVIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse. Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are blaOXA-48 and blaNDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem.

Published
2020
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21. Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

Author

Mulder, T, van den Kluytmans-Bergh, MFQ, Vlaminckx, B, Roos, D, De Smet, AM, Cappel, R, Verheijen, P, Brandt - Kerkhof, Alexandra, Smits, A, van der Vorm, E, Bathoorn, E, Etten, B, Veenemans, J, Weersink, A, Vos, Greet, van't Veer, N, Nikolakopoulos, S, Bonten, M, Kluytmans, J, Mulder, T, van den Kluytmans-Bergh, MFQ, Vlaminckx, B, Roos, D, De Smet, AM, Cappel, R, Verheijen, P, Brandt - Kerkhof, Alexandra, Smits, A, van der Vorm, E, Bathoorn, E, Etten, B, Veenemans, J, Weersink, A, Vos, Greet, van't Veer, N, Nikolakopoulos, S, Bonten, M, and Kluytmans, J

Published
2020

23. Proportion of asylum seekers carrying multi-drug resistant microorganisms is persistently increased after arrival in the Netherlands

Author

Ravensbergen, S.J. Louka, C. Ott, A. Rossen, J.W. Cornish, D. Pournaras, S. Bathoorn, E. Stienstra, Y.

Abstract

Background: Several studies have shown a high prevalence of multi-drug resistant organisms (MDRO) amongst asylum seekers when compared to the general population. The aim of this study is to assess the duration of MDRO carriage in this population. Methods: Data were retrospectively collected between January 1st 2014 through December 31st 2016. Study material included screening samples for MDRO carriage and clinical samples from asylum seekers in need of medical care. The study focused on methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Enterobacteriaceae (MDRE). The rates of MRSA and MDRE detected were calculated every four weeks after arrival in the Netherlands. Results: Samples from 2091 asylum seekers were included. 1270 (60.7%) were female, median age was 26 years (IQR 20-34) and median number of days in the Netherlands until first sample was 67 (IQR 4-235). In the patients' first obtained samples, the rate of MRSA varied between 4.5 and 13.0% per time interval after arrival. The rate of MDRE fluctuated between 7.4% and 25.0%. No particular decline in positivity rates in first obtained samples was observed after arrival in the Netherlands. In the group of asylum seekers who arrived more than one year ago, MRSA was isolated in a percentage of 5.1% (n = 273, median months after arrival 34.1 (IQR 16.5-63.1)) and MDRE in 9.4% (n = 276, median months after arrival 35.4 (IQR 17-65)). Conclusion: To our knowledge, this is the first study demonstrating that carriage rate of MDRO in asylum seekers remains high even after prolonged stay in the Netherlands. Longitudinal data on MDRO carriage after arrival in countries with a low MDRO prevalence are needed to determine optimal screening strategies, infection control measures and empirical antibiotic therapy. © 2019 The Author(s).

Published
2019

25. Identification of a Novel Genomic Island Associated with vanD -Type Vancomycin Resistance in Six Dutch Vancomycin-Resistant Enterococcus faecium Isolates

Author

Top, Janetta, primary, Sinnige, Jan C., additional, Brouwer, Ellen C., additional, Werner, Guido, additional, Corander, Jukka, additional, Severin, Juliëtte A., additional, Jansen, Rogier, additional, Bathoorn, E., additional, Bonten, Marc J. M., additional, Rossen, John W. A., additional, and Willems, Rob J. L., additional

Published
2018
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26. Identification of a novel genomic island associated with vand-type vancomycin resistance in six Dutch vancomycin-resistant enterococcus faecium isolates

Author

Top, Janetta, Sinnige, Jan C., Brouwer, Ellen C., Werner, Guido, Corander, Jukka, Severin, Juliëtte A., Jansen, Rogier, Bathoorn, E., Bonten, Marc J.M., Rossen, John W.A., Willems, Rob J.L., Top, Janetta, Sinnige, Jan C., Brouwer, Ellen C., Werner, Guido, Corander, Jukka, Severin, Juliëtte A., Jansen, Rogier, Bathoorn, E., Bonten, Marc J.M., Rossen, John W.A., and Willems, Rob J.L.

Published
2018

27. Identification of a novel genomic island associated with vand-type vancomycin resistance in six Dutch vancomycin-resistant enterococcus faecium isolates

Author

MMB Infectiepreventie, Infection & Immunity, MMB opleiding Arts microbioloog, Epi Infectieziekten, JC onderzoeksprogramma Infectieziekten, Top, Janetta, Sinnige, Jan C., Brouwer, Ellen C., Werner, Guido, Corander, Jukka, Severin, Juliëtte A., Jansen, Rogier, Bathoorn, E., Bonten, Marc J.M., Rossen, John W.A., Willems, Rob J.L., MMB Infectiepreventie, Infection & Immunity, MMB opleiding Arts microbioloog, Epi Infectieziekten, JC onderzoeksprogramma Infectieziekten, Top, Janetta, Sinnige, Jan C., Brouwer, Ellen C., Werner, Guido, Corander, Jukka, Severin, Juliëtte A., Jansen, Rogier, Bathoorn, E., Bonten, Marc J.M., Rossen, John W.A., and Willems, Rob J.L.

Published
2018

32. Astrovirus outbreak at a pediatric hematology and hematopoietic stem cell transplant unit despite strict hygiene rules

Author

MMB opleiding Arts microbioloog, Infectieziekten patientenzorg, Child Health, Infection & Immunity, Haematologie, Regenerative Medicine and Stem Cells, MMB Medische Staf, SCT patientenzorg, Van Der Doef, H. P J, Bathoorn, E., Van Der Linden, M. P M, Wolfs, T. F W, Minderhoud, A. L C, Bierings, M. B., Wensing, A. M J, Lindemans, C. A., MMB opleiding Arts microbioloog, Infectieziekten patientenzorg, Child Health, Infection & Immunity, Haematologie, Regenerative Medicine and Stem Cells, MMB Medische Staf, SCT patientenzorg, Van Der Doef, H. P J, Bathoorn, E., Van Der Linden, M. P M, Wolfs, T. F W, Minderhoud, A. L C, Bierings, M. B., Wensing, A. M J, and Lindemans, C. A.

Published
2016

34. Extensive colonization with carbapenemase-producing microorganisms in Romanian burn patients: infectious consequences from the Colectiv fire disaster.

Author

Pirii, L. E., Friedrich, A. W., Rossen, J. W.A., Vogels, W., Beerthuizen, G. I. J. M., Nieuwenhuis, M. K., Kooistra-Smid, A. M. D., and Bathoorn, E.

Subjects
BURN patients, INFECTION prevention, BURNS & scalds complications, CARBAPENEMASE, MOLECULAR epidemiology
Abstract

Health care of severe burn patients is highly specialized and may require international patient transfer. Burn patients have an increased risk of developing infections. Patients that have been hospitalized in countries where carbapenemase-producing microorganisms (CPMO) are endemic may develop infections that are difficult to treat. In addition, there is a risk on outbreaks with CPMOs in burn centers. This study underlines that burn patients may extensively be colonized with CPMOs, and it provides best practice recommendations regarding clinical microbiology and infection control. We evaluated CPMO-carriage and wound colonization in a burn patient initially treated in Romania, and transported to the Netherlands. The sequence types and acquired beta-lactamase genes of highly-resistant microorganisms were derived from next generation sequencing data. Next, we searched literature for reports on CPMOs in burn patients. Five different carbapenemase-producing isolates were cultured: two unrelated OXA-48-producing Klebsiella pneumoniae isolates, OXA-23-producing Acinetobacter baumanii, OXA-48-producing Enterobacter cloacae, and NDM-1-producing Providencia stuartii. Also, multi-drug resistant Pseudomonas aeruginosa isolates were detected. Among the sampling sites, there was high variety in CPMOs. We found 46 reports on CPMOs in burn patients. We listed the epidemiology of CPMOs by country of initial treatment, and summarized recommendations for care of these patients based on these reports and our study. [ABSTRACT FROM AUTHOR]

Published
2018
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35. Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: A case report

Author

Bathoorn, E., Escobar Salazar, N., Sepehrkhouy, S., Meijer, M., de Cock, H., Haas, P.J., Bathoorn, E., Escobar Salazar, N., Sepehrkhouy, S., Meijer, M., de Cock, H., and Haas, P.J.

Abstract

Background: Aspergillus tubingensis is a black Aspergillus belonging to the Aspergillus section Nigri, which includes species that morphologically resemble Aspergillus niger. Recent developments in species determination have resulted in clinical isolates presumed to be Aspergillus niger being reclassified as Aspergillus tubingensis by sequencing. We present a report of a patient with an osteomyelitis of the maxillary bone with a probable invasive Aspergillus tubingensis infection.Case presentation: We describe an immune compromised patient suffering from osteomyelitis of the maxillary bone after tooth extraction. The osteomyelitis probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis. Histologic examination of biopsy samples showed osteomyelitis, and inflammation of the surrounding connective tissue. Cultures of the alveolar wound grew Aspergillus tubingensis. The patient was treated with liposomal amphoterocin B, which was changed to oral treatment with voriconazole based on susceptibility testing (MIC for voriconazole was 1 μg/ml).Conclusion: This case shows that Aspergillus tubingensis may have the potential to cause severe invasive infections in immunocompromised hosts. A larger proportion of Aspergillus tubingensis isolates are less susceptible to azoles compared to Aspergillus niger. Therefore, correct species identification and susceptibility testing is crucial for the choice of anti-fungal treatment, screening of azole resistance, and characterization of the pathogenic potential of the various species within Aspergillus section Nigri. © 2013 Bathoorn et al.; licensee BioMed Central Ltd., Background: Aspergillus tubingensis is a black Aspergillus belonging to the Aspergillus section Nigri, which includes species that morphologically resemble Aspergillus niger. Recent developments in species determination have resulted in clinical isolates presumed to be Aspergillus niger being reclassified as Aspergillus tubingensis by sequencing. We present a report of a patient with an osteomyelitis of the maxillary bone with a probable invasive Aspergillus tubingensis infection.Case presentation: We describe an immune compromised patient suffering from osteomyelitis of the maxillary bone after tooth extraction. The osteomyelitis probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis. Histologic examination of biopsy samples showed osteomyelitis, and inflammation of the surrounding connective tissue. Cultures of the alveolar wound grew Aspergillus tubingensis. The patient was treated with liposomal amphoterocin B, which was changed to oral treatment with voriconazole based on susceptibility testing (MIC for voriconazole was 1 μg/ml).Conclusion: This case shows that Aspergillus tubingensis may have the potential to cause severe invasive infections in immunocompromised hosts. A larger proportion of Aspergillus tubingensis isolates are less susceptible to azoles compared to Aspergillus niger. Therefore, correct species identification and susceptibility testing is crucial for the choice of anti-fungal treatment, screening of azole resistance, and characterization of the pathogenic potential of the various species within Aspergillus section Nigri. © 2013 Bathoorn et al.; licensee BioMed Central Ltd.

Published
2013

36. Primary Epstein-Barr virus infection with neurological complications

Author

Bathoorn, E., Vlaminckx, B.J., Schoondermark-Stolk, S., Donders, A.R.T., Meulen, M. van der, Thijsen, S.F., Bathoorn, E., Vlaminckx, B.J., Schoondermark-Stolk, S., Donders, A.R.T., Meulen, M. van der, and Thijsen, S.F.

Abstract

Item does not contain fulltext, Several case studies have reported on neurological complications caused by a primary Epstein-Barr virus (EBV) infection. We aimed to investigate the viral loads and the clinical and inflammatory characteristics of this disease entity. We evaluated all 84 cases in which the EBV polymerase chain reaction test (PCR) was requested on cerebrospinal fluid (CSF) for the period 2003-2008. Fourteen patients with proven neuroborreliosis served as the control group. Nine patients were diagnosed with a primary EBV infection and neurological symptoms (median age 36 y; 4 male). Viral DNA copies in CSF were detected by PCR in 7 of 9 patients. The presenting symptoms were meningeal signs, epileptic insults, polyradiculomyelitis, polyradiculitis, and/or sudden cognitive disorders. All EBV cases had a pleocytosis with significantly increased mononuclear leukocytes as compared to the neuroborreliosis group (median 99% interquartile range (96-100%) versus 90% (86-97%). In cases with a primary EBV infection, viral loads ranged from 43 to 3202 copies/ml in CSF and from 61 to 15,595 copies/ml in serum. Seventy-eight percent of the cases had a positive PCR on CSF. This study provides criteria for diagnosing neurological disease during primary EBV infection. Primary EBV infections in immune competent persons can cause a broad range of neurological symptoms, with lymphocytic and monocytic inflammation both in blood and CSF.

Published
2011

43. Case report: Carbapenemase-producing enterobacteriaceae in an asylum seeker with multidrug-resistant tuberculosis

Author

Ravensbergen, S.J. Louka, C. Lokate, M. Bathoorn, E. Pournaras, S. Van Der Werf, T.S. De Lange, W.C.M. Stienstra, Y. Akkerman, O.W.

Abstract

A Syrian asylum seeker with multidrug-resistant tuberculosis (TB) developed a bronchopleural fistula after pneumonectomy. Although screening tests were negative on admission, carbapenemase-producing Enterobacteriaceae were cultured after a few months ofTBtreatment. Prevalence of multidrug-resistant organisms is reported to be increased in asylum seekers compared with the general Dutch population. Arduous conditions during transit and interrupted health care delivery in our patient led to multiple-resistant microorganisms that complicated treatment. Copyright © 2018 by The American Society of Tropical Medicine and Hygiene.

44. Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: a case report

Author

Bathoorn Erik, Escobar Salazar Natalia, Sepehrkhouy Shahrzad, Meijer Martin, de Cock Hans, and Haas Pieter-Jan

Subjects
Aspergillus tubingensis, Aspergillus section nigri, Invasive mould infection, Species identification, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Aspergillus tubingensis is a black Aspergillus belonging to the Aspergillus section Nigri, which includes species that morphologically resemble Aspergillus niger. Recent developments in species determination have resulted in clinical isolates presumed to be Aspergillus niger being reclassified as Aspergillus tubingensis by sequencing. We present a report of a patient with an osteomyelitis of the maxillary bone with a probable invasive Aspergillus tubingensis infection. Case presentation We describe an immune compromised patient suffering from osteomyelitis of the maxillary bone after tooth extraction. The osteomyelitis probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis. Histologic examination of biopsy samples showed osteomyelitis, and inflammation of the surrounding connective tissue. Cultures of the alveolar wound grew Aspergillus tubingensis. The patient was treated with liposomal amphoterocin B, which was changed to oral treatment with voriconazole based on susceptibility testing (MIC for voriconazole was 1 μg/ml). Conclusion This case shows that Aspergillus tubingensis may have the potential to cause severe invasive infections in immunocompromised hosts. A larger proportion of Aspergillus tubingensis isolates are less susceptible to azoles compared to Aspergillus niger. Therefore, correct species identification and susceptibility testing is crucial for the choice of anti-fungal treatment, screening of azole resistance, and characterization of the pathogenic potential of the various species within Aspergillus section Nigri.

Published
2013
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45. The agreement between bronchoalveolar lavage, bronchial wash and sputum culture: a retrospective study.

Author

Post AE, Bathoorn E, Postma DF, Slebos DJ, and Akkerman OW

Subjects
Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Pseudomonas aeruginosa isolation & purification, Sputum microbiology, Bronchoalveolar Lavage methods, Bronchoalveolar Lavage Fluid microbiology
Abstract

Purpose: Bronchoalveolar lavage is commonly used in clinical practice for unresolved pneumonia. However, bronchoalveolar lavage is not suitable for all patients as it is an invasive procedure and can worsen oxygenation. The diagnostic value of bronchial wash and sputum has been debated extensively over the years. In this study, we aim to compare the diagnostic value in several pathogens of bronchoalveolar lavage and bronchial wash, and secondarily bronchoalveolar lavage and sputum., Methods: We retrospectively included all adult patients in our hospital who underwent bronchoalveolar lavage, bronchial wash, and where sputum sampling was done between January 1st of 2018 and December 31st of 2021. The intraclass correlation coefficient was computed for the three tests., Results: In total, 308 patients were included. We found a level of correlation of 0.819 and 0.865, respectively, between bronchoalveolar lavage and bronchial wash for two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. For Stenotrophomonas maltophilia and Aspergillus fumigatus, we found an intraclass correlation coefficient of 0.568 and 0.624, respectively. Between bronchoalveolar lavage and sputum, we found varying levels of agreement., Conclusion: Our study shows reasonably well agreement levels between bronchoalveolar lavage and bronchial wash, suggesting that bronchial wash could potentially be an alternative to bronchoalveolar lavage., (© 2024. The Author(s).)

Published
2024
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46. Nosocomial transmission of tet(x3) , bla NDM-1 and bla OXA-97 -carrying Acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the Netherlands, March to August 2021.

Author

Talsma DT, Monteiro R, Flores-Vallejo RDC, Heuvelmans M, Le TN, Hendrickx AP, Rosema S, Maat I, van Dijl JM, and Bathoorn E

Subjects
Humans, Netherlands epidemiology, Plasmids genetics, Disease Outbreaks, Bacterial Proteins genetics, Carbapenems pharmacology, Intensive Care Units, Acinetobacter baumannii genetics, Acinetobacter baumannii drug effects, Acinetobacter baumannii isolation & purification, Acinetobacter baumannii enzymology, Acinetobacter Infections microbiology, Acinetobacter Infections epidemiology, Microbial Sensitivity Tests, Tetracyclines pharmacology, Anti-Bacterial Agents pharmacology, Cross Infection microbiology, Cross Infection epidemiology, beta-Lactamases genetics, Drug Resistance, Multiple, Bacterial genetics
Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important pathogen causing serious nosocomial infections. We describe an outbreak of CRAb in an intensive care unit in the Netherlands in 2021. During an outbreak of non-resistant A. baumannii , while infection control measures were in place, CRAb isolates carrying highly similar bla NDM-1 - and tet(x3)- encoding plasmids were isolated from three patients over a period of several months. The chromosomal and plasmid sequences of the CRAb and non-carbapenemase-carrying A. baumannii isolates cultured from patient materials were analysed using hybrid assemblies of short-read and long-read sequences. The CRAb isolates revealed that the CRAb outbreak consisted of two different strains, carrying similar plasmids. The plasmids contained multiple antibiotic resistance genes including the tetracycline resistance gene tet(x3) , and the bla NDM-1 and bla OXA-97 carbapenemase genes. We determined minimal inhibitory concentrations (MICs) for 13 antibiotics, including the newly registered tetracycline antibiotics eravacycline and omadacycline. The CRAb isolates showed high MICs for tetracycline antibiotics including eravacycline and omadacycline, except for minocycline which had a low MIC. In this study we show the value of sequencing multidrug-resistant A. baumannii for outbreak tracking and guiding outbreak mitigation measures.

Published
2024
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47. The complete genome sequence of unculturable Mycoplasma faucium obtained through clinical metagenomic next-generation sequencing.

Author

Sabat AJ, Durfee T, Baldwin S, Akkerboom V, Voss A, Friedrich AW, and Bathoorn E

Subjects
Humans, Mycoplasma Infections microbiology, Mycoplasma Infections diagnosis, Whole Genome Sequencing methods, Lung Transplantation, Prophages genetics, Interspersed Repetitive Sequences genetics, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Metagenomics methods, Genome, Bacterial, High-Throughput Nucleotide Sequencing, Mycoplasma genetics, Mycoplasma isolation & purification, Mycoplasma classification
Abstract

Introduction: Diagnosing Mycoplasma faucium poses challenges, and it's unclear if its rare isolation is due to infrequent occurrence or its fastidious nutritional requirements., Methods: This study analyzes the complete genome sequence of M. faucium , obtained directly from the pus of a sternum infection in a lung transplant patient using metagenomic sequencing., Results: Genome analysis revealed limited therapeutic options for the M. faucium infection, primarily susceptibility to tetracyclines. Three classes of mobile genetic elements were identified: two new insertion sequences, a new prophage (phiUMCG-1), and a species-specific variant of a mycoplasma integrative and conjugative element (MICE). Additionally, a Type I Restriction-Modification system was identified, featuring 5'-terminally truncated hsdS pseudogenes with overlapping repeats, indicating the potential for forming alternative hsdS variants through recombination., Conclusion: This study represents the first-ever acquisition of a complete circularized bacterial genome directly from a patient sample obtained from invasive infection of a primary sterile site using culture-independent, PCR-free clinical metagenomics., Competing Interests: Authors TD and SB are employees of the company DNASTAR, Inc. SB is a minor shareholder in DNASTAR, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sabat, Durfee, Baldwin, Akkerboom, Voss, Friedrich and Bathoorn.)

Published
2024
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48. Neonatal Elizabethkingia anophelis meningitis originating from the water reservoir of an automated infant milk dispenser, the Netherlands, February 2024.

Author

Brandsema BR, Fleurke GJ, Rosema S, Schins EM, Helfferich J, and Bathoorn E

Subjects
Humans, Infant, Newborn, Genome, Bacterial, Milk, Netherlands, Flavobacteriaceae, Flavobacteriaceae Infections diagnosis, Flavobacteriaceae Infections drug therapy, Flavobacteriaceae Infections epidemiology, Meningitis
Abstract

Elizabethkingia anophelis is a multidrug-resistant pathogen causing high mortality and morbidity in adults with comorbidities and neonates. We report a Dutch case of E. anophelis meningitis in a neonate, clonally related to samples taken from an automated infant milk dispenser located at the family's residence. We inform about the emergence of E. anophelis and suggest molecular surveillance in hospitals and other health settings. This is the first case connecting an automated formula dispenser to an invasive infection in a neonate.

Published
2024
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49. Uncovering the spread of drug-resistant bacteria through next-generation sequencing based surveillance: transmission of extended-spectrum β-lactamase-producing Enterobacterales by a contaminated duodenoscope.

Author

Cimen C, Bathoorn E, Loeve AJ, Fliss M, Berends MS, Nagengast WB, Hamprecht A, Voss A, and Lokate M

Subjects
Humans, Bacteria genetics, beta-Lactamases genetics, Klebsiella pneumoniae genetics, High-Throughput Nucleotide Sequencing, Duodenoscopes, Sepsis
Abstract

Contamination of duodenoscopes is a significant concern due to the transmission of multidrug-resistant organisms (MDROs) among patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), resulting in outbreaks worldwide. In July 2020, it was determined that three different patients, all had undergone ERCP with the same duodenoscope, were infected. Two patients were infected with bla CTX-M-15 encoding Citrobacter freundii, one experiencing a bloodstream infection and the other a urinary tract infection, while another patient had a bloodstream infection caused by bla SHV-12 encoding Klebsiella pneumoniae. Molecular characterization of isolates was available as every ESBL-producing isolate undergoes Next-Generation Sequencing (NGS) for comprehensive genomic analysis in our center. After withdrawing the suspected duodenoscope, we initiated comprehensive epidemiological research, encompassing case investigations, along with a thorough duodenoscope investigation. Screening of patients who had undergone ERCP with the implicated duodenoscope, as well as a selection of hospitalized patients who had ERCP with a different duodenoscope during the outbreak period, led to the discovery of three additional cases of colonization in addition to the three infections initially detected. No microorganisms were detected in eight routine culture samples retrieved from the suspected duodenoscope. Only after destructive dismantling of the duodenoscope, the forceps elevator was found to be positive for bla SHV-12 encoding K. pneumoniae which was identical to the isolates detected in three patients. This study highlights the importance of using NGS to monitor the transmission of MDROs and demonstrates that standard cultures may fail to detect contaminated medical equipment such as duodenoscopes., (© 2024. The Author(s).)

Published
2024
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50. Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome.

Author

Westgeest AC, Schippers EF, Rosema S, Fliss MA, Kuijper EJ, Zwittink RD, Lokate M, Wouthuyzen-Bakker M, Lambregts MMC, and Bathoorn E

Subjects
Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cohort Studies, Ciprofloxacin, Carrier State drug therapy, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections drug therapy
Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11-15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms., (© 2024. The Author(s).)

Published
2024
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