Laboratory of Medical Microbiology and Infectious Diseases

Zwolle, Netherlands

Laboratory of Medical Microbiology and Infectious Diseases

Zwolle, Netherlands
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van Ingen J.,Radboud University Nijmegen | Kohl T.A.,Molecular and Experimental Mycobacteriology | Kohl T.A.,German Center for Infection Research | Kranzer K.,National Mycobacteriology Reference Laboratory | And 56 more authors.
The Lancet Infectious Diseases | Year: 2017

Background: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. Methods: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. Findings: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. Interpretation: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. Funding: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance. © 2017 Elsevier Ltd.


Bruijnesteijn van Coppenraet L.E.S.,Laboratory of Medical Microbiology and Infectious Diseases | Swanink C.M.A.,Alysis Zorggroep | van Zwet A.A.,Alysis Zorggroep | Nijhuis R.H.T.,Alysis Zorggroep | And 3 more authors.
Journal of Virological Methods | Year: 2010

Two molecular assays were compared with real-time RT-PCR and viral culture for simultaneous detection of common viruses from respiratory samples: a multiplex ligation-dependant probe amplification (MLPA) and a dual priming oligonucleotide system (DPO). In addition, the positive detections of MLPA and DPO were identified using two different automatic electrophoresis systems. A panel of 168 culture-positive and negative samples was tested by the molecular assays for the presence of influenza A and B virus, respiratory syncytial virus, human metapneumovirus, rhinovirus, coronaviruses, parainfluenza viruses and adenovirus.One hundred and twenty-nine (77%) samples were positive as detected by at least one method. Sixty-nine (41%) samples were positive by cell culture (excluding human metapneumovirus and coronaviruses), 116 (69%) by RT-PCR, 127 (76%) by MLPA and 100 (60%) by DPO. The MLPA yielded results in one attempt for all samples included while 12 (7.2%) samples had to be repeated by the DPO assay due to inconclusive results. The MLPA assay performed well in combination with either electrophoresis system, while the performance of the DPO assay was influenced by the electrophoresis systems.Both molecular assays are comparable with real-time RT-PCR, more sensitive than viral culture and can detect dual infections easily. Results can be obtained within 1 day. © 2010 Elsevier B.V.


Fraaij P.L.A.,Erasmus University Rotterdam | Fraaij P.L.A.,Erasmus MC Sophia Childrens Hospital | Van Der Vries E.,Erasmus University Rotterdam | Beersma M.F.C.,Erasmus University Rotterdam | And 15 more authors.
Journal of Infectious Diseases | Year: 2011

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days) compared with 14 days (range, 6-21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated. © The Author 2011.


Van der Bij A.K.,National Institute for Public Health and the Environment RIVM | Frentz D.,National Institute for Public Health and the Environment RIVM | Bonten M.J.M.,University Utrecht | Cohen Stuart J.W.T.,Medical Center Alkmaar | And 49 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016

Objectives: The objective of this study was to determine time trends in the rate of Gram-positive cocci in 42 Dutch ICUs that continuously used or did not use selective oropharyngeal decontamination (SOD) or selective decontamination of the digestive tract (SDD) and ICUs that introduced SOD/SDD. Methods: The Dutch Surveillance System on Antibiotic Resistance was used to determine monthly rates of Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium isolates, including resistant phenotypes, in blood and respiratory tract specimens from 2008 to 2013. Per patient, the last isolate per species per month was selected, and cumulative rates per 100 beds per month were determined. Time trends were analysed by multilevel Poisson regression. Results: Eighteen ICUs used SOD/SDD (1296 months), 13 did not use SOD/SDD (936 months) and 11 introduced SOD/SDD (373 months before and 419 months after introduction). There was no significant increase in the rate of Gram-positive cocci in ICUs that used SOD/SDD. Introduction of SOD/SDD was associated with increased rates of S. aureus (β = 0.018, 95% CI 0.006-0.030) and E. faecalis isolates (β = 0.028, 95% CI 0.006-0.051) in respiratory tract specimens. Numbers of resistant phenotypes remained low, and an observed increase in E. faecium isolates (β = 0.033, 95% CI 0.012-0.054), 97% of which were resistant to ampicillin, in the absence of SOD/SDD disappeared after the introduction of SOD/SDD. Conclusions: In ICUs with a low endemicity of resistance, introduction of SOD/SDD was associated with increased rates of S. aureus and E. faecalis isolates, but not with resistant phenotypes. Continuous 5 year use of SOD/SDD was not associated with increased isolation of Gram-positive cocci. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Leverstein-van Hall M.A.,National Institute for Public Health and the Environment RIVM | Leverstein-van Hall M.A.,Bronovo Hospital | Waar K.,Center for Infectious Diseases Friesland | Muilwijk J.,National Institute for Public Health and the Environment RIVM | And 47 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2013

Objectives: The CLSI recommends a fixed 2:1 ratio of co-amoxiclav for broth microdilution susceptibility testing of Enterobacteriaceae, while EUCASTrecommends a fixed 2 mg/L clavulanate concentration. The aims of this study were: (i) to determine the influence of a switch fromCLSI to EUCASTmethodology on Escherichia coli susceptibility rates; (ii) to compare susceptibility results obtained using EUCAST-compliant microdilution with those from disc diffusion and the Etest; and (iii) to evaluate the clinical outcome of patients with E. coli sepsis treated with co-amoxiclav in relation to the susceptibility results obtained using either method. Methods: Resistance rateswere determined in three laboratories that switched fromCLSI to EUCASTcards with the Phoenix system (Becton Dickinson) as well as in 17 laboratories that continued to use CLSI cards with the VITEK 2 system (bioMérieux). In one laboratory, isolateswere simultaneously tested by both the Phoenix system and either disc diffusion (n=471) or the Etest (n=113). Medical and laboratory records were reviewed for E. coli sepsis patients treated with co-amoxiclav monotherapy. Results: Only laboratories that switched methodology showed an increase in resistance rates - from19% in 2010 to 31% in 2011 (P,0.0001). All isolates that tested susceptible by microdilution were also susceptible by disc diffusion or the Etest, but of 326 isolates that tested resistant by microdilution, 43% and 59% tested susceptible by disc diffusion and the Etest, respectively. Among the 89 patients included there was a better correlation between clinical response and measured MICs using the Phoenix system than the Etest. Conclusions: EUCASTmethodology resulted in higherco-amoxiclav E. coli resistance rates than CLSI methodology, but correlated better with clinical outcome. EUCAST-compliant microdilution and disc diffusion provided discrepant results. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Houben A.J.M.,National Institute for Public Health and the Environment RIVM | Houben A.J.M.,Health Science University | Oostdijk E.A.N.,University Utrecht | van der Voort P.H.J.,Onze Lieve Vrouwe Gasthuis | And 53 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: Selective oropharyngeal decontamination (SOD) and selective decontamination of the digestive tract (SDD) are associated with improved outcomes among patients in intensive care units (ICUs), but uncertainty remains about their long-term effects on resistance levels. We determined trends in antibiotic resistance among Gram-negative bacteria in 38 Dutch ICUs using and not using SOD/SDD. Methods: The Infectious Disease Surveillance Information System-Antibiotic Resistance (ISIS-AR) was used to identify all Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. isolates from blood and respiratory tract specimens from ICUs between January 2008 and April 2012. Per patient, the last isolate per species per specimen per month was selected to determine cumulative resistance rates (per 100 beds/month) for colistin, tobramycin, ciprofloxacin, ceftazidime and cefotaxime/ceftriaxone in ICUs that continuously used or did not use SOD/SDD, and ICUs that introduced SOD/SDD. Time trends were analysed by multilevel Poisson regression. Results: Seventeen ICUs continuously used SOD/SDD (859 months), 13 did not use SOD/SDD (663 months) and 8 introduced SOD/SDD (223 and 117 months before and after introduction). There were no discernible trends in antibiotic resistance among 637 blood isolates. For the 8353 respiratory isolates, resistance to cefotaxime/ceftriaxone increased in ICUs that did not use SOD/SDD (P<0.001) and decreased in those that continuously used SOD/SDD (P=0.04), as did resistance to ciprofloxacin (P<0.001). The introduction of SOD/SDD was followed by statistically significant reductions in resistance rates for all antimicrobial agents. Conclusions: Continuous use of SOD/SDD was associated with decreasing trends for resistance to cefotaxime/ceftriaxone and ciprofloxacin. The introduction of SOD/SDD was associated with reductions in resistance rates for all antimicrobial agents included. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Kohler P.,University of Zürich | Kuster S.P.,University of Zürich | Bloemberg G.,University of Zürich | Schulthess B.,University of Zürich | And 22 more authors.
European Heart Journal | Year: 2015

Aims: We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. Methods and results: Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. Conclusion: Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens. © The Author 2015.

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