The majority of antimicrobial susceptibility testing (AST) in Dutch medical microbiology laboratories (MMLs) is performed using the automated system VITEK2 or Phoenix. One of the Phoenix users... Show moreThe majority of antimicrobial susceptibility testing (AST) in Dutch medical microbiology laboratories (MMLs) is performed using the automated system VITEK2 or Phoenix. One of the Phoenix users noted a high percentage of gentamicin resistance in Proteus mirabilis compared to national resistance data. We therefore performed a descriptive analysis comparing gentamicin and tobramycin minimum inhibitory concentration (MIC) distributions for Enterobacterales and non-fermenters as measured using VITEK2 and Phoenix. Routine susceptibility data from 5 MMLs using Phoenix and 31 using VITEK2 with complete data in the Dutch national surveillance system for antimicrobial resistance from January 2016 to December 2021 were included. A panel of 12 discrepant isolates was sent to Becton Dickinson for confirmation. In general, Phoenix measured higher MICs, with discrepancies being most prevalent for Proteus, Providencia, Morganella, Serratia, and Acinetobacter species (borderline susceptibility for gentamicin ranging from 1% for VITEK2 to 67% for Phoenix systems), and less, but still clinically relevant, for Escherichia coli (1%-12%). Furthermore, we observed a yearly increase in resistance for Proteus and Providencia species measured by Phoenix. Similar discrepancies were found for tobramycin. The company confirmed our findings on all strains. Significantly more false aminoglycoside borderline susceptible and resistant Enterobacterales were found using Phoenix compared to the VITEK2 system. These findings should be taken into consideration in the development of clinical treatment guidelines for patients with sepsis.IMPORTANCEAntimicrobial sensitivity data are important to guide antimicrobial therapy. In microbiological laboratories, routine sensitivity measurements are typically performed with automated testing systems such as VITEK2 and Phoenix. Using data from the Dutch national surveillance system for antimicrobial resistance over a 6-year period, we found that the measured minimum inhibitory concentrations for aminoglycosides in Enterobacterales and non-fermenters were too high for the Phoenix system. In addition, we observed a yearly increase in resistance for several species measured by Phoenix. These findings might have consequences for clinical treatment of patients with sepsis.Antimicrobial sensitivity data are important to guide antimicrobial therapy. In microbiological laboratories, routine sensitivity measurements are typically performed with automated testing systems such as VITEK2 and Phoenix. Using data from the Dutch national surveillance system for antimicrobial resistance over a 6-year period, we found that the measured minimum inhibitory concentrations for aminoglycosides in Enterobacterales and non-fermenters were too high for the Phoenix system. In addition, we observed a yearly increase in resistance for several species measured by Phoenix. These findings might have consequences for clinical treatment of patients with sepsis. Show less
Vendrik, K.E.W.; Kuijper, J.; Dimmendaal, M.; Silvis, W.; Denie-Verhaegh, E.; Boer, A. de; ... ; MRSA Consortium 2022
In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resist-ant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first... Show moreIn this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resist-ant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next -generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community -onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance. Show less
Court, J.R. de la; Woudt, S.H.S.; Schoffelen, A.F.; Heijmans, J.; Jonge, N.A. de; Bruggen, T. van der; ... ; Schade, R.P. 2022
Objectives Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third... Show moreObjectives Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third-generation cephalosporins (3GC) is increasing. In order to explore the value of using surveillance cultures to guide empirical treatment e.g. choosing between carbapenem versus ceftazidime- we aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-resistant GNB (3GC-R GNB) bacteraemia that was preceded by 3GC-R GNB colonization. Methods Using 11 years of data (2008-2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of 3GC-R GNB in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Colonization was defined as availability of any GNB surveillance isolate in the year before, independent of the causative micro-organism (time-paired isolates). Results We included 3887 patients, representing 4142 episodes of bacteraemia. GNB were identified in 715/4142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In 139 of these 221 patients a time-paired surveillance culture was available. In 76.2% (106/139) of patients these surveillance cultures already showed 3GC-R GNB isolates in the year prior to the culture date of the 3GC-R GNB positive blood isolate. Conclusions This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of the use of surveillance-cultures to guide empirical therapy to restrict the empirical use of carbapenems in this population. Show less
Background: The Netherlands is currently considered a low endemic country for carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE), experiencing only... Show moreBackground: The Netherlands is currently considered a low endemic country for carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE), experiencing only sporadic hospital outbreaks. This study aims to describe susceptibility to carbapenems and the epidemiology of carbapenemase production in Enterobacterales in the Netherlands in 2017-2019. Methods: Three complementary nationwide surveillance systems are in place to monitor carbapenem susceptibility in the Netherlands. Routine antimicrobial susceptibility test results from medical microbiology laboratories were used to study phenotypic susceptibility of Escherichia coli and Klebsiella pneumoniae. Pathogen surveillance (of all Enterobacterales species) and mandatory notifications were used to describe the characteristics of CPE positive isolates and affected persons. Results: The prevalence of isolates with gradient strip test-confirmed elevated meropenem (> 0.25 mg/L) or imipenem (> 1 mg/L) minimum inhibitory concentration (MIC) in the Netherlands was very low in 2017-2019, with percentages of 0.06% in E. coli and 0.49% in K. pneumoniae, and carbapenem resistances of 0.02% and 0.18%, respectively. A total of 895 unique species/carbapenemase-encoding allele combinations of CPE from 764 persons were submitted between 2017 and 2019, with the annual number of submissions increasing slightly each year. Epidemiological data was available for 660 persons. Screening because of presumed colonisation risk was the reason for sampling in 70.0% (462/660) of persons. Hospitalization abroad was the most common risk factor, being identified in 45.9% of persons. Conclusions: Carbapenem resistance of E. coli and K. pneumoniae remains low in the Netherlands. The annual number of CPE isolates slightly increased during the period 2017-2019. Recent hospitalization abroad is the main risk factor for acquisition of CPE. Show less
Lestrade, P.P.A.; Buil, J.B.; Beek, M.T. van der; Kuijper, E.J.; Dijk, K. van; Kampinga, G.A.; ... ; Verweij, P.E. 2020
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
Kooi, T.I.I. van der; Boshuizen, H.; Wille, J.C.; Greeff, S.C. de; Dissel, J.T. van; Schoffelen, A.F.; Gaalen, R.D. van 2019
Seven hospitals participated in the Dutch national surveillance for ventilator-associated pneumonia (VAP) and its risk factors. We analysed time-independent and time-dependent risk factors for VAP... Show moreSeven hospitals participated in the Dutch national surveillance for ventilator-associated pneumonia (VAP) and its risk factors. We analysed time-independent and time-dependent risk factors for VAP using the standard Cox regression and the flexible Weighted Cumulative Effects method (WCE) that evaluates both current and past exposures. The prospective surveillance of intensive care patients aged. 16 years and ventilated. 48 hours resulted in the inclusion of 940 primary ventilation periods, comprising 7872 ventilation days. The average VAP incidence density was 10.3/1000 ventilation days. Independent risk factors were age (16-40 years at increased risk: HR 2.42 95% confidence interval 1.07-5.50), COPD (HR 0.19 [0.04-0.78]), current sedation score (higher scores at increased risk), current selective oropharyngeal decontamination (HR 0.19 [0.04-0.91]), jet nebulizer (WCE, decreased risk), intravenous antibiotics for selective decontamination of the digestive tract (ivSDD, WCE, decreased risk), and intravenous antibiotics not for SDD (WCE, decreased risk). The protective effect of ivSDD was afforded for 24 days with a delay of 3 days. For some time-dependent variables, the WCE model was preferable over standard Cox proportional hazard regression. The WCE method can furthermore increase insight into the active time frame and possible delay herein of a time-dependent risk factor. 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
