Genetische variatie van zomereik in een aanplant en een spontane verjonging

Uit een vergelijking van de genetische variatie in een aangeplant bos en een natuurlijke verjonging (Amerongen) met een natuurlijk bos (De Meinweg) blijkt dat het bosbeheer geen waarneembaar effect heeft. Door de bijdrage van vele, onbekende vaders is de genetische variatie overal groot. Het onderzoek werd uitgevoerd met microsatelliet-analys

Invloed van de bosbouwpraktijk op de genetische samenstelling van eikenbossen

Hebben de verschillen in aanleg, ontwikkeling en beheer van eikenbossen een grote invloed op de genetische samenstelling (diversiteit) van de bossen? Drie bossen (bosreservaat De Meintweg bij Roermond, militair terrein De Stompert bij Soesterberg, en boswachterij Amerongen) werden bemonsterd om de genetische herkomst te bepalen. De voorkomende haplotypes zeggen iets over het autochtoon zijn van de bossen en vertonen een relatie met de intensiteit van behee

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

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the

Ciprofloxacin : Use and resistance in Community, Nursing Home and Hospital

The aim of the studies described in this thesis was to analyze some aspects of ciprofloxacin use and clinical and (molecular) epidemiology of ciprofloxacin resistance in different settings, both within hospitals (chapter 3,4 and 6), community and nursing homes (chapter 2 and 5). With its broad spectrum against gram negative organisms and favorable pharmacokinetics, ciprofloxacin use has increased over the last two decades, as did resistance against ciprofloxacin. Chapter 2 describes a nation-wide epidemiological analysis of culture-proven Campylobacter infections in the Netherlands over the years 2000-2004 and the effect of region, degree of urbanization and season on the incidence of campylobacteriosis and development of resistance. High stable rates of resistance to fluoroquinolones (35%) were observed and resistance was higher in travel related infections (54%) than in endemic infections (33%). The high resistance rates to fluoroquinolones warrants reconsideration of its use as drug of first choice in the empiric treatment of gastrointestinal infections in the Netherlands. In chapter 3 the effects of intervention to reduce and improve ciprofloxacin use in a hospital have been described. Despite relatively low baseline ciprofloxacin consumption, intervention led to 3-4 fold sustained reduction in the use of ciprofloxacin and significant improvement in quality of ciprofloxacin prescription. Close collaboration within a hospital between medical microbiologists and clinicians is an important condition to reduce liberal and inappropriate use of antibiotics. Chapter 4 describes our randomized double-blind placebo-controlled trial where ciprofloxacin use appeared not beneficial at all in reducing occurrence of significant bacteriuria and urinary tract infection after catheter removal. We determined the prevalence and molecular epidemiology of ESBL-producing and of ciprofloxacin-resistant Enterobacteriaceae in a teaching hospital and nursing homes in its immediate catchment area in a point prevalence and retrospective analysis in chapter 5. Our findings demonstrate a persistently high prevalence of ciprofloxacin-resistant (26%) and ESBL-producing (7%) Enterobacteriaceae in nursing home residents. In chapter 6 we investigated the evolution of ciprofloxacin resistance and molecular epidemiology of clinical E. coli isolates in haematology patients receiving ciprofloxacin prophylaxis on the population and individual patient level. We provide evidence for cross-transmission of ciprofloxacin resistant E. coli and in vivo mutation to a resistant phenotype of previously sensitive E. coli strains (in 7% of patients). In our study we observe that in 27% of patients ciprofloxacin-resistant E. coli strains can be demonstrated. Resistance to antibiotics is becoming an increasingly important worldwide problem. Inappropriate use of antibiotics is considered to be the most important reason for development of antibiotic resistance. Antibiotic pressure in the community, hospitals and nursing homes, should be reduced by a shift to treatment based on results of microbiologic investigation rather than empiric treatment. Given large quantities of antibiotics currently use in veterinary medicine, judicious and targeted use of antibiotics in clinical medicine alone will not be enough to prevent ever increasing levels of resistance. The use of veterinary antimicrobial drugs associated with induction of resistance to antibiotics in humans should be limited, preferably by government regulations

Genetische variatie van zomereik in een aanplant en een spontane verjonging

Uit een vergelijking van de genetische variatie in een aangeplant bos en een natuurlijke verjonging (Amerongen) met een natuurlijk bos (De Meinweg) blijkt dat het bosbeheer geen waarneembaar effect heeft. Door de bijdrage van vele, onbekende vaders is de genetische variatie overal groot. Het onderzoek werd uitgevoerd met microsatelliet-analys

Appropriateness of empirical treatment and outcome in bacteremia caused by extended-spectrum-β-lactamase-producing bacteria

We studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients with bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing bacteria in eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive patients with ESBL bacteremia (due to Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae) between 2008 and 2010. In this cohort (median age of 65 years; 24 patients were <18 years of age), many had comorbidities, such as malignancy (34%) or recurrent urinary tract infection (UTI) (15%). One hundred forty episodes (60%) were nosocomial, 54 (23%) were otherwise health care associated, and 38 (16%) were community acquired. The most frequent sources of infection were UTI (42%) and intra-abdominal infection (28%). Appropriate therapy within 24 h after bacteremia onset was prescribed to 37% of all patients and to 54% of known ESBL carriers. The day 30 mortality rate was 20%. In a multivariable analysis, a Charlson comorbidity index of ≥3, an age of ≥75 years, intensive care unit (ICU) stay at bacteremia onset, a non-UTI bacteremia source, and presentation with severe sepsis, but not inappropriate therapy within <24 h (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 0.68 to 3.45), were associated with day 30 mortality. Further assessment of confounding and a stratified analysis for patients with UTI and non-UTI origins of infection did not reveal a statistically significant effect of inappropriate therapy on day 30 mortality, and these results were insensitive to the possible misclassification of patients who had received β-lactam-β-lactamase inhibitor combinations or ceftazidime as initial treatment. In conclusion, ESBL bacteremia occurs mostly in patients with comorbidities requiring frequent hospitalization, and 84% of episodes were health care associated. Factors other than inappropriate therapy within <24 h determined day 30 mortality. Copyrigh