Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR adj) ¼ 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR adj ¼ 1.89, 95% CI: 1.06, 3.36) and distal (IRR adj ¼ 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR adj ¼ 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR adj ¼ 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors. biological markers; case-control studies; colorectal neoplasms; oxidative stress Abbreviations: CI, confidence interval; CRC, colorectal cancer; FRAP, ferric reducing ability of plasma; ICD-10, International Classification of Diseases, Tenth Revision; IRR, incidence rate ratio; ROM, reactive oxygen metabolites; ROS, reactive oxygen species. Worldwide, colorectal cancer (CRC) is the third most common cancer, accounting for approximately 1.2 million new cases and 608,000 deaths per year (1). Several endogenous factors, as well as lifestyle and dietary factors, related to CRC risk have been identified (2). A diet rich in fruit and vegetables and containing antioxidants in abundance has been shown to be associated with a lower risk of cancer, including CRC (3, 4). Moreover, oxidative

Background Invasive infections by group A S treptococcus (iGAS, Streptococcus pyogenes ) have a winter seasonality which largely coincides with the season for influenza and other respiratory viruses. Influenza superinfections with GAS have been described to occur regularly and to show a severe clinical picture with high mortality. We aimed to study the extent to which influenza A and B viruses (IAV and IBV), respiratory syncytial virus (RSV) and rhinovirus circulation contribute to iGAS incidence and severity. Methods Time‐series regression models were built to explore the temporal associations between weekly laboratory counts of IAV, IBV, RSV and rhinovirus as independent variables and weekly counts of GAS disease notifications or laboratory GAS cultures as dependent variables. Results The weekly number of IAV detections showed a significant temporal association with the number of notifications of streptococcal toxic shock syndrome (STSS), a severe complication of iGAS. Depending on the season, up to 40% of all notified STSS cases was attributable to IAV circulation. Besides STSS, none of the other iGAS manifestations were associated with a respiratory virus. Conclusions Our study found an ecological temporal association between IAV and STSS, the most severe complication of iGAS. Future studies are needed to confirm this association and assess the possible preventability of STSS by influenza vaccination, especially in the age group 60 years and older.

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.

Background 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.

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...

a , k , on behalf of the ISIS-AR study group l , 1

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.

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