Primary Health Care Laboratory

Utrecht, Netherlands

Primary Health Care Laboratory

Utrecht, Netherlands
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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.


Leverstein-van Hall M.A.,University Utrecht | Leverstein-van Hall M.A.,National Institute for Public Health and the Environment RIVM | Dierikx C.M.,Central Veterinary Institute of Wageningen UR | Cohen Stuart J.,University Utrecht | And 11 more authors.
Clinical Microbiology and Infection | Year: 2011

Intestinal carriage of extended-spectrum beta-lactamase (ESBL) -producing bacteria in food-producing animals and contamination of retail meat may contribute to increased incidences of infections with ESBL-producing bacteria in humans. Therefore, distribution of ESBL genes, plasmids and strain genotypes in Escherichia coli obtained from poultry and retail chicken meat in the Netherlands was determined and defined as 'poultry-associated' (PA). Subsequently, the proportion of E. coli isolates with PA ESBL genes, plasmids and strains was quantified in a representative sample of clinical isolates. The E. coli were derived from 98 retail chicken meat samples, a prevalence survey among poultry, and 516 human clinical samples from 31 laboratories collected during a 3-month period in 2009. Isolates were analysed using an ESBL-specific microarray, sequencing of ESBL genes, PCR-based replicon typing of plasmids, plasmid multi-locus sequence typing (pMLST) and strain genotyping (MLST). Six ESBL genes were defined as PA (blaCTX-M-1, blaCTX-M-2, blaSHV-2, blaSHV-12, blaTEM-20, blaTEM-52): 35% of the human isolates contained PA ESBL genes and 19% contained PA ESBL genes located on IncI1 plasmids that were genetically indistinguishable from those obtained from poultry (meat). Of these ESBL genes, 86% were blaCTX-M-1 and blaTEM-52 genes, which were also the predominant genes in poultry (78%) and retail chicken meat (75%). Of the retail meat samples, 94% contained ESBL-producing isolates of which 39% belonged to E. coli genotypes also present in human samples. These findings are suggestive for transmission of ESBL genes, plasmids and E. coli isolates from poultry to humans, most likely through the food chain. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.


Kelder J.C.,University Utrecht | Kelder J.C.,St Antonius Hospital | Cramer M.J.,University Utrecht | Verweij W.M.,Primary Health Care Laboratory | And 2 more authors.
Journal of Cardiac Failure | Year: 2011

Background: In patients suspected of new slow-onset heart failure, data on the comparative diagnostic performance of automated B-type natriuretic peptide (BNP) assays are scarce. Methods and Results: Two hundred patients referred to a heart failure outpatient diagnostic facility underwent standard diagnostic work-up including echocardiography. The reference standard for the diagnosis of heart failure was an expert panel conclusion. N-terminal pro-BNP on Elecsys and BNP on Axsym and Centaur machines were measured in a single batch. Data were available for 172 patients; 51 had heart failure (29.7%). All 3 tests had high c-statistic values. An intermediate-risk subset of 111 patients (34% with heart failure) was created by excluding patients with very high or very low probability based on history and physical examination, the subgroup most in need of an additional test. Applying different thresholds for ruling heart failure in or out, the positive predicted values in this "gray zone" group were 75%, 76%, and 72%, respectively, and the negative predictive values 83%, 71%, and 85%, with the remaining 50% of patients having ∼18% probability of heart failure. Conclusion: In practice, a valid diagnosis in patients suspected of slow-onset heart failure remains elusive for many in the absence of echocardiographic imaging. © 2011 Elsevier Inc. All rights reserved.


Rijkaart D.C.,VU University Amsterdam | Coupe V.M.H.,VU University Amsterdam | Van Kemenade F.J.,VU University Amsterdam | Heideman D.A.M.,VU University Amsterdam | And 7 more authors.
British Journal of Cancer | Year: 2010

Background:We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.Methods:We used data of 25 871 women (aged 30-60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3 +), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.Results:Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.Conclusions:The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing. © 2010 Cancer Research UK. All rights reserved.


Rijkaart D.C.,VU University Amsterdam | Rijkaart D.C.,Primary Health Care Laboratory | Berkhof J.,VU University Amsterdam | Van Kemenade F.J.,VU University Amsterdam | And 7 more authors.
International Journal of Cancer | Year: 2010

We studied the effectiveness of high-risk human papillomavirus (hrHPV) triage for immediate colposcopy in women with borderline or mild dyskaryosis (BMD). In the Utrecht province of the Netherlands, women aged 30-60 years who participated in the regular cervical screening programme were offered hrHPV testing and cytology (intervention group) or cytology only (control group). In the intervention group (n = 337), women with BMD were immediately referred for colposcopy only if the sample was hrHPV positive. Women with a hrHPV negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if and when the repeat test result was positive (BMD or worse). In the control group (n = 329), referral of women with BMD was delayed until cytology was repeatedly positive at 6 or 18 months. The CIN3 detection rates were 10.7% (36/337) in the intervention group and 6.4% (21/329) in the control group (p = 0.047). Moreover, hrHPV triaging resulted in shorter time to diagnosis (154 vs. 381 days). Although the number of colposcopy referrals was 51.5% higher in the intervention group than in the control group, the medical costs per detected CIN3 were slightly lower ([euro] 4781 vs. [euro] 6235). If, in addition, hrHPV negative women had been referred back to routine screening at baseline, the CIN3 rate would have been 10.1% (34/337) and colposcopy rate would only have been 30.4% higher than in the control group. This study shows that hrHPV triaging of women with BMD is at least as effective for detecting CIN3 as repeat cytology, also when hrHPV negative women are referred back to routine screening. © 2009 UICC.


Rijkaart D.C.,VU University Amsterdam | Berkhof J.,VU University Amsterdam | Van Kemenade F.J.,VU University Amsterdam | Coupe V.M.H.,VU University Amsterdam | And 7 more authors.
British Journal of Cancer | Year: 2012

Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.Methods:In all, 25 871 women (29-61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3). Results were adjusted for non-attendance at repeat testing.Results:The hrHPV-positive women with abnormal cytology had a CIN3 risk of 42.2% (95% confidence interval (CI): 36.4-48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72-7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3 risk to only 1.6% (95% CI: 0.6-4.9) if the repeat test was normal. The CIN3 risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29-33 years of age) (9.1%; 95% CI: 5.6-14.3) than among older women (3.0%; 95% CI: 1.5-5.5).Conclusion:Primary hrHPV screening with cytology triage in women aged ≥30 years is an effective way to stratify women on CIN3 risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening. © 2012 Cancer Research UK All rights reserved.


Rijkaart D.C.,VU University Amsterdam | Berkhof J.,VU University Amsterdam | Van Kemenade F.J.,VU University Amsterdam | Coupe V.M.H.,VU University Amsterdam | And 8 more authors.
International Journal of Cancer | Year: 2012

High-risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high-grade intraepithelial neoplasia (CIN). To avoid over-referral to colposcopy and overtreatment, hrHPV-positive women require triage testing and/or followup. A total of 25,658 women (30-60 years) enrolled in a population-based cohort study had an adequate baseline Pap smear and hrHPV test. The end-point was cumulative two-year risk of CIN grade 3 or worse (CIN3+). In a post-hoc analysis, fourteen triage/followup strategies for hrHPV-positive women (n = 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6-99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4-60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2-36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1-99.8%). Triage hrHPV-positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy. Copyright © 2011 UICC.

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