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

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

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

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.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.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

The prevalence of disease clusters in older adults with multiple chronic diseases - a systematic literature review

Contains fulltext : 126145.pdf (publisher's version ) (Open Access)BACKGROUND: Since most clinical guidelines address single diseases, treatment of patients with multimorbidity, the co-occurrence of multiple (chronic) diseases within one person, can become complicated. Information on highly prevalent combinations of diseases can set the agenda for guideline development on multimorbidity. With this systematic review we aim to describe the prevalence of disease combinations (i.e. disease clusters) in older patients with multimorbidity, as assessed in available studies. In addition, we intend to acquire information that can be supportive in the process of multimorbidity guideline development. METHODS: We searched MEDLINE, Embase and the Cochrane Library for all types of studies published between January 2000 and September 2012. We included empirical studies focused on multimorbidity or comorbidity that reported prevalence rates of combinations of two or more diseases. RESULTS: Our search yielded 3070 potentially eligible articles, of which 19 articles, representing 23 observational studies, turned out to meet all our quality and inclusion criteria after full text review. These studies provided prevalence rates of 165 combinations of two diseases (i.e. disease pairs). Twenty disease pairs, concerning 12 different diseases, were described in at least 3 studies. Depression was found to be the disease that was most commonly clustered, and was paired with 8 different diseases, in the available studies. Hypertension and diabetes mellitus were found to be the second most clustered diseases, both with 6 different diseases. Prevalence rates for each disease combination varied considerably per study, but were highest for the pairs that included hypertension, coronary artery disease, and diabetes mellitus. CONCLUSIONS: Twenty disease pairs were assessed most frequently in patients with multimorbidity. These disease combinations could serve as a first priority setting towards the development of multimorbidity guidelines, starting with the diseases with the highest observed prevalence rates and those with potential interacting treatment plans

Triple saut : enseigner la répartition des bonds

Contains fulltext : 153445.pdf (publisher's version ) (Open Access)BACKGROUND: To support the management of multimorbid patients in primary care, evidence is needed on prevalent multimorbidity patterns. OBJECTIVE: To identify the common and distinctive multimorbidity patterns. METHODS: Clinical data of 120480 patients (>/=55 years) were extracted from 158 general practices in 2002-11. Prevalence rates of multimorbidity were analyzed (overall, and for 24 chronic diseases), adjusted for practice, number of diseases and patients' registration period; differentiated between patients 55-69 and >/=70 years. To investigate multimorbidity patterns, prevalence ratios (prevalence rate index-disease group divided by that in the non-index-disease group) were calculated for patients with heart failure, diabetes mellitus, migraine or dementia. RESULTS: Multiple membership multilevel models showed that the overall adjusted multimorbidity rate was 86% in patients with >/=1 chronic condition, varying from 70% (migraine) to 98% (heart failure), 38% had >/=4 chronic diseases. In patients 55-69 years, 83% had multimorbidity. Numerous significant prevalence ratios were found for disease patterns in heart failure patients, ranging from 1.2 to 7.7, highest ratio for chronic obstructive pulmonary disease-cardiac dysrhythmia. For diabetes mellitus, dementia or migraine patients highest ratios were for heart failure-visual disorder (2.1), heart failure-depression (3.9) and depression-back/neck disorder (2.1), respectively (all P-values <0.001). CONCLUSIONS: Multimorbidity management in general practice can be reinforced by knowledge on the clinical implications of the presence of the comprehensive disease patterns among the elderly patients, and those between 55 and 69 years. Guideline developers should be aware of the complexity of multimorbidity. As a consequence of this complexity, it is even more important to focus on what matters to a patient with multimorbidity in general practice

Bij iedere huisarts evenveel pillen? inter-praktijkvariatie in polyfarmacie*.

Doel: Onderzoeken wat de variatie is in het percentage oudere patiënten met polyfarmacie tussen huisartsenpraktijken, in de groep mensen die minstens één geneesmiddel gebruikt, en in hoeverre patiënt- en praktijkkenmerken met deze variatie samenhangen. Opzet: Cohortonderzoek. Methode: We gebruikten gegevens van huisartsenpraktijken – gekoppeld met gegevens van apotheken – die deelnamen aan NIVEL Zorgregistraties eerste lijn en de Stichting Farmaceutische Kengetallen. We includeerden patiënten van 55 jaar en ouder die ten minste 1 geneesmiddel gebruikten in 2012. Van de 45.731 geïncludeerde patiënten uit 126 huisartsenpraktijken bepaalden we het percentage patiënten met polyfarmacie. Vervolgens onderzochten we met multilevel logistische regressieanalyses wat de inter-praktijkvariatie was. Verschillende patiënt- en praktijkkenmerken werden toegevoegd aan de modellen, als mogelijke verklarende variabelen voor de variatie. Resultaten: De spreiding in het percentage oudere patiënten met polyfarmacie tussen praktijken liep van 12,4 tot 30,1%, nadat gecorrigeerd was voor verschillen in patiënt- en praktijkkenmerken. Gemiddeld had 19,8% van de patiënten polyfarmacie. Hoe ouder patiënten waren, des te groter de kans op polyfarmacie. Ook het aantal en het type chronische aandoeningen hing sterk positief samen met het hebben van polyfarmacie. In mindere mate gold dit voor sociaal-economische status. Praktijkkenmerken waren nauwelijks van invloed op de verschillen tussen praktijken. Conclusie: Er is aanzienlijke inter-praktijkvariatie in het percentage oudere patiënten met polyfarmacie. Omdat dit niet komt door verschillen in de patiëntpopulatie of door praktijkkenmerken, lijken zorgverleners een grote rol te spelen bij de verschillen in het voorschrijven. Vervolgonderzoek naar de verklaring en mogelijke ongewenste effecten van deze verschillen is belangrijk. (aut. ref.

Medication management strategy for older people with polypharmacy in general practice: a qualitative study on prescribing behaviour in primary care

BACKGROUND: For older patients with polypharmacy, medication management is a process of careful deliberation that needs periodic adjustment based on treatment effects and changing conditions. Because of the heterogeneity of the patient group, and limited applicability of current guidelines, it is difficult for GPs to build up a routine. AIM: To gain insight into GPs' medication management strategies for patients with polypharmacy, and to explore the GPs' perspectives and needs on decision-making support to facilitate this medication management. DESIGN AND SETTING: Two focus group meetings with Dutch GPs, discussing four clinical vignettes of patients with multimorbidity and polypharmacy. METHOD: Questions about medication management of the vignettes were answered individually; the strategy chosen in each case was discussed in plenary. Analysis followed a Framework approach. RESULTS: In total, 12 GPs described a similar strategy regarding the patients' medication management: defining treatment goals; determining primary goals; and adjusting medications based on the treatment effect, GPs' and patients' preferences, and patient characteristics. There was variation in the execution of this strategy between the GPs. The GPs would like to discuss their choices with other professionals and they valued structured medication reviews with the patient, as well as quick and practical support tools that work on demand. CONCLUSION: To facilitate decision making, a more extensive and structured collaboration between healthcare professionals is desired, as well as support to execute structured medication reviews with eligible patients, and some on-demand tools for individual consultations

[Inter-practice variation in polypharmacy prevalence amongst older patients in primary care]

Item does not contain fulltextPURPOSE: Complex medication management in older people with multiple chronic conditions can introduce practice variation in polypharmacy prevalence. This study aimed to determine the inter-practice variation in polypharmacy prevalence and examine how this variation was influenced by patient and practice characteristics. METHODS: This cohort study included 45,731 patients aged 55 years and older with at least one prescribed medication from 126 general practices that participated in NIVEL Primary Care Database in the Netherlands. Medication dispensing data of the year 2012 were used to determine polypharmacy. Polypharmacy was defined as the chronic and simultaneous use of at least five different medications. Multilevel logistic regression models were constructed to quantify the polypharmacy prevalence variation between practices. Patient characteristics (age, gender, socioeconomic status, number, and type of chronic conditions) and practice characteristics (practice location and practice population) were added to the models. RESULTS: After accounting for differences in patient and practice characteristics, polypharmacy rates varied with a factor of 2.4 between practices (from 12.4% to 30.1%) and an overall mean of 19.8%. Age and type of conditions were highly positively associated with polypharmacy, and to a lesser extent a lower socioeconomic status. CONCLUSIONS: Considerable variation in polypharmacy rates existed between general practices, even after accounting for patient and practice characteristics, which suggests that there is not much agreement concerning medication management in this complex patient group. Initiatives that could reduce inappropriate heterogeneity in medication management can add value to the care delivered to these patients

The interactive web-based program MSmonitor for self-management and multidisciplinary care in multiple sclerosis: concept, content, and pilot results

Contains fulltext : 152846.pdf (publisher's version ) (Open Access)BACKGROUND: There is a growing need to offer persons with multiple sclerosis (PwMS) possibilities for self-management and to integrate multidisciplinary health data. In 2009-2014 we developed a patient-reported outcome based, interactive, web-based program (MSmonitor) for (self-)monitoring, self-management and integrated, multidisciplinary care in MS. METHODS: The notions underlying the MSmonitor concept and the program's elements are described. We analyze MSmonitor's role in the self-management of fatigue by retrospective comparison of fatigue and health-related quality of life (HRQoL) before and after usage of specific elements of MSmonitor, and by a correlative analysis between frequency of usage and fatigue change. RESULTS: After a step-wise development the program comprises six validated questionnaires: Multiple Sclerosis Impact Profile, Modified Fatigue Impact Scale-5 items (MFIS-5), Hospital Anxiety and Depression Scale, Multiple Sclerosis Quality of Life-54 items, and the 8-item Leeds Multiple Sclerosis Quality of Life (LMSQoL) questionnaires; two inventories: Medication and Adherence Inventory, Miction Inventory; two diaries: Activities Diary, Miction Diary; and two functionalities: e-consult and personal e-logbook. The program is now used in 17 hospitals by 581 PwMS and their neurologists, MS nurses, physical therapists, rehabilitative doctors, continence nurses, and family doctors. Those PwMS (N=105) who used the LMSQoL and MFIS-5 questionnaires at least twice in a period of up to 6 months, showed improved HRQoL (P<0.026). In the subgroup (N=56) who had also used the Activities Diary twice or more, the frequency of diary usage correlated modestly with the degree of fatigue improvement (r=0.292; P=0.028). CONCLUSION: MSmonitor is an interactive web-based program for self-management and integrated care in PwMS. Pilot data suggest that the repeated use of the short MFIS-5 and LMSQoL questionnaires is associated with an increase in HRQoL, and that a repeated use of the Activities Diary might contribute to the self-management of fatigue

Third-generation cephalosporin and carbapenem resistance in Streptococcus mitis/oralis. Results from a nationwide registry in the Netherlands

Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc