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... Show moreBackground.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.A group of bacteria that cause difficult-to-treat infections in humans is methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to monitor changes in the spread of MRSA, their disease causing potential and resistance to antibiotics used to treat MRSA infections. MRSA from patients and their contacts in the Netherlands were collected over a period of 12 years and characterized. This revealed new types of MRSA emerged and others disappeared. An increasing number of MRSA produces a protein called PVL toxin, enabling MRSA to cause more severe infections. Also, some people appear to carry MRSA without any disease for more than a year. These findings suggest an increasing disease potential of MRSA and possible unnoticed sources of infection. Consequently, it is important to maintain monitoring of these infections to minimize MRSA spread.Schouls et al. characterize 43,321 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained between 2008 and 2019 in the Netherlands. Genomic changes occur in the MRSA population, with increases in the proportion of PVL-positive MRSA. Show less
Grootveld, R. van; Beek, M.T. van der; Janssen, N.A.F.; Erguen, M.; Dijk, K. van; Bethlehem, C.; ... ; CAPA20 Study Grp 2023
Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential... Show morePurpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment.Materials and methods: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria.Results: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy.Conclusions: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation. Show less
Pothast, C.R.; Dijk, K. van; Pool, E.S.; Halkes, C.J.M.; Heemskerk, M.H.M.; Tjon, J.M.L. 2022
We investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We... Show moreWe investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency increased from 7.6% (95% CI 5.9%-9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%-17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutations. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Our survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests. Show less
Prehn, J. van; Triest, M.I. van; Altorf-van der Kuil, W.; Dijk, K. van; Stuart, J.W.T.C.; Weersink, A.J.L.; ... ; Dutch Natl AMR Surveillance Study 2019
After penetrating keratoplasty had been the preferred method for the treatment of corneal disorders for almost a century, the introduction of lamellar keratoplasty techniques has changed the... Show moreAfter penetrating keratoplasty had been the preferred method for the treatment of corneal disorders for almost a century, the introduction of lamellar keratoplasty techniques has changed the field of corneal transplantation substantially over the last two decades. These lamellar keratoplasty techniques provide several advantages over penetrating keratoplasty: anterior lamellar keratoplasty may potentially improve graft survival by preserving the healthy recipient endothelium in the management of corneal stromal diseases, and endothelial keratoplasty has improved the predictability and speed of visual rehabilitation for treating endothelial disorders, mainly by leaving the anterior corneal surface intact. The latest innovation in the field of endothelial keratoplasty is Descemet membrane endothelial keratoplasty (DMEK), in which only the Descemet membrane and endothelium are replaced by donor tissue. The trend towards more selective and minimally invasive transplantation techniques has also led to the development of new treatment options for patients with (advanced) keratoconus, including the mid-stromal implantation of an isolated donor Bowman layer, referred to as Bowman layer-transplantation. This thesis focusses on the feasibility and clinical outcomes of these two modern lamellar keratoplasty techniques, i.e. DMEK for endothelial disorders, and Bowman layer-transplantation for advanced keratoconus. Show less
Donner, N.R.; Arteaga, A.; Geurds, A.; Dijk, K. van 2017
In 2015 and 2016, the Proyecto Arqueológico Centro de Nicaragua ( Pacen) conducted several fieldwork seasons which focused on surface survey and mound recording. The main goal of this research was... Show moreIn 2015 and 2016, the Proyecto Arqueológico Centro de Nicaragua ( Pacen) conducted several fieldwork seasons which focused on surface survey and mound recording. The main goal of this research was to systematically document the synchronic and diachronic variability in pre-Hispanic material culture found throughout the Mayales River subbasin, particularly in the valley north of Juigalpa, in the department of Chontales. The study started as a full-coverage, high intensity surface survey in a 52 sq km area, as well as the recording of all sites featuring architecture within a 42 sq km subarea. Surface ceramics were mainly found on the riverbanks, while chipped stone presented lower densities distributed uniformly throughout the area, similar to groundstone, which occurred in even lesser quantities. Ceramic and chipped stone distribution and frequency seem to be related to raw material procurement practices rather than the chronological depth of sites with architectural features. In the process, 1,300 mounds were documented during 2015 and 2016. Including the previously registered site of Aguas Buenas, the total of 1,679 mounds was divided in 47 clusters, following specific environmental and material culture patterning. Preliminary results of this study suggest that pre-Hispanic communities in the research area formed a historically complex social landscape Show less
Veerdonk, F.L. van de; Kolwijck, E.; Lestrade, P.P.A.; Hodiamont, C.J.; Rijnders, B.J.A.; Paassen, J. van; ... ; Dutch-Belgian Mycoses Study Grp 2017
A survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a... Show moreA survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a background of emerging azole resistance in Aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the UMCs. Azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. Voriconazole remained first choice for invasive aspergillosis in 13 out of 16 hospitals. In documented azole resistance 14 out of 16 centres treated patients with liposomal amphotericin B. Show less
A.K. van der bij; Dijk, K. van; Muilwijk, J.; Thijsen, S.F.T.; Notermans, D.W.; Greeff, S. de; ... ; ISIS-AR Study Grp 2012
