Clostridium difficile infections (CDIs) are frequent in hospitals, but also seem to increase in the community. Here, we aim to determine the incidence of CDI in general practice and to evaluate current testing algorithms for CDI. Three Dutch laboratories tested all unformed faeces (12,714) for C. difficile when diagnostic testing (for any enteric pathogen) was requested by a general practitioner (GP). Additionally, a nested case-control study was initiated, including 152 CDI patients and 304 age and sex-matched controls. Patients were compared using weighted multivariable logistic regression. One hundred and ninety-four samples (1.5%) were positive for C. difficile (incidence 0.67/10,000 patient years). This incidence was comparable to that of Salmonella spp. Compared with diarrhoeal controls, CDI was associated with more severe complaints, underlying diseases, antibiotic use and prior hospitalization. In our study, GPs requested a test for C. difficile in 7% of the stool samples, thereby detecting 40% of all CDIs. Dutch national recommendations advise testing for C. difficile when prior antibiotic use or hospitalization is present (18% of samples). If these recommendations were followed, 61% of all CDIs would have been detected. In conclusion, C. difficile is relatively frequent in general practice. Currently, testing for C. difficile is rare and only 40% of CDI in general practice is detected. Following recommendations that are based on traditional risk factors for CDI, would improve detection of CDI.

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 ¼ 388, 43%), Escherichia coli (n ¼ 264, 30%) and Enterobacter cloacae complex (n ¼ 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 bla OXA-48 being predominant (38%, 336/892), followed by bla NDM-1 (16%, 145/892). For the first time in the Netherlands, bla OXA-181 , bla OXA-232 and bla VIM-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 bla OXA-48 and bla NDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem.

Antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, but the estimated number of additional recurrent episodes in the Netherlands (40 per year) was rather limited.

Knowledge of beta-lactam resistance rates in Streptococcus mitis group bacteria is especially important in neutropenic haematological patients as adequate empirical antibiotic treatment (often including agents like meropenem [1]) is paramount. EUCAST guidelines allow one to infer viridans group streptococci (VGS) beta-lactam susceptibility from benzylpenicillin susceptibility; penicillin-resistant isolates should be tested for individual agents. Few studies reported the association between penicillin resistance and broad-spectrum beta-lactam resistance in VGS [2,3], and data from Northern European countries is lacking. Here, we first describe the prevalence of beta-lactam resistance in S. mitis/oralis in The Netherlands. Second, we describe the association between penicillin MIC and broad-spectrum beta-lactam resistance.The Dutch national surveillance system for antimicrobial resistance (ISIS-AR) [4], covering 44 out of 56 Dutch clinical microbiology laboratories in 2017, was searched for susceptibility results of S. mitis/oralis isolates for (benzyl)penicillin, amoxicillin/ampicillin, cefotaxime/ceftriaxone, and meropenem from 2013 through 2017.ISIS-AR collects susceptibility test results of all bacterial isolates of collaborating laboratories. The analysis was limited to the first isolate of each patient. Patients whose first isolate was not tested for penicillin susceptibility were excluded.To avoid bias due to selective testing, for each antibiotic only laboratories testing 50% of isolates were included. Forty-one laboratories were included for analyses on penicillin susceptibility, 24 laboratories for amoxicillin/ampicillin, and 23 for cefotaxime/ceftriaxone. Meropenem was tested in 15 laboratories; here the inclusion rule was not applied, as this resulted in a significant impact on the number of isolates for analysis. All selected laboratories used EUCAST guidelines, except one laboratory in 2013. MIC breakpoint for susceptibility is 0.25 mg/L for penicillin, 0.5 mg/L for amoxicillin/ampicillin and cefotaxime/ceftriaxone, and 2 mg/L for meropenem.Of 4164 S. mitis/oralis isolates tested for penicillin, 3634 were reported susceptible (87.2%), 281 intermediate (6.7%), and 249 resistant (6.0%). Of 2019 isolates with amoxicillin/ampicillin susceptibility reported, 117 isolates were reported resistant (5.8%) to either agent. Of 2079 isolates with cefotaxime/ceftriaxone susceptibility reported, 159 were resistant (7.6%). Of 306 isolates with meropenem susceptibility reported, four were resistant (1.3%). Percentages of broad-spectrum beta-lactam resistance by penicillin susceptibility category is shown in the Table S1.For amoxicillin/ampicillin susceptible isolates, the median penicillin MIC with automated testing was 0.06 mg/L (IQR 0.06e0.12; n ¼ 875), for intermediate isolates 1.0 mg/L (IQR 0.5e2.0; n ¼ 55), and for resistant isolates 2.0 mg/L (IQR 2.0e4.0; n ¼ 51). Results with gradient testing were similar: for susceptible isolates median penicillin MIC was 0.047 mg/L (IQR 0.023e0.094; n ¼ 327), for intermediat...

Objectives 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.