Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study.

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.

Antibiotic Resistance and the Risk of Recurrent Bacteremia.

Background: Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of recurrent bacteremia associated with resistance. Methods: We extracted antimicrobial susceptibility testing data on blood isolates from the Dutch surveillance system for antimicrobial resistance between 2008 and 2017. First and first recurrent (4-30 days) bacteremia episodes were categorized as susceptible, single nonsusceptible, or co-nonsusceptible to third-generation cephalosporins without or with carbapenems (Enterobacteriaceae), ceftazidime without or with carbapenems (Pseudomonas species), aminopenicillins without or with vancomycin (Enterococcus species), or as methicillin-sensitive/-resistant S. aureus (MSSA/MRSA). We calculated risks of recurrent bacteremia after nonsusceptible vs susceptible first bacteremia, estimated the crude population attributable effect of resistance for the Netherlands, and calculated risks of nonsusceptible recurrent bacteremia after a susceptible first episode. Results: Risk ratios for recurrent bacteremia after a single- and co-nonsusceptible first episode, respectively, vs susceptible first episode, were 1.7 (95% confidence interval [CI], 1.5-2.0) and 5.2 (95% CI, 2.1-12.4) for Enterobacteriaceae, 1.3 (95% CI, 0.5-3.1) and 5.0 (95% CI, 2.9-8.5) for Pseudomonas species, 1.4 (95% CI, 1.2-1.7) and 1.6 (95% CI, 0.6-4.2) for Enterococcus species, and 1.6 (95% CI, 1.1-2.4) for MRSA vs MSSA. The estimated population annual number of recurrent bacteremias associated with nonsusceptibility was 40. The risk of nonsusceptible recurrent bacteremia after a susceptible first episode was at most 0.4% (Pseudomonas species). Conclusions: Although antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, the estimated annual number of additional recurrent episodes in the Netherlands (40) was rather limited.

Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition.

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)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 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) = 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.

Epidemiology of carbapenem-resistant and carbapenemase-producing Enterobacterales in the Netherlands 2017-2019.

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.

[Important rise in antibiotic resistance rates inHelicobacter pyloriin the Netherlands]. / Verontrustende toename van antibioticaresistentie bijHelicobacter pylori.

OBJECTIVE: Description of the changing patterns of antibiotic resistance in Helicobacter pylori infection in the Netherlands. DESIGN: Retrospective database study using the Dutch infectious disease surveillance information system-antibiotic resistance (ISIS-AR). METHOD: In the ISIS-AR database antibiotic resistance data are reported by 46 microbiologic laboratories in the Netherlands. For the present study, data from 16 centres were used with a 10 year period of reporting H. pylori resistance data, from 1 January 2010 till 1 January 2020, for amoxycillin, levofloxacin, claritrhromycin, tetracyclin and metronidazole. RESULTS: In 2019 Antimicrobial resistance rates in the Netherlands were 1% for tetracycline, 5% for amoxycillin, 23%% for levofloxacin, 46% for metronidazole and 47% for clarithromycin. The combined resistance rate for clarithromycin and metronidazole was 29%. Significantly higher resistance rates were found in female patients for amoxycillin (8% vs 1%), clarithromycin (53% vs 38%) and metronidazole (52% vs 38%). From 2010 to 2019, a significant rise in resistance rates was found for amoxycillin (0% - 5%), clarithromycin (7% - 40%), metronidazole (14% - 45%) and for the clarithromycin and metronidazole combination (2% - 29%). CONCLUSION: There was an important rise in antibiotic resistance rates in H. pylori in the Netherlands. For optimal H. pylori treatment bismuth-based therapies should become available again in the Netherlands. Treatment of H. pylori should be based on the individual antibiotic resistance profile and be in concordance with the principles of antibiotic stewardship. Guidelines for treatment of H. pylori in the Netherlands should be adapted and have a better correlation with International guidelines and best practices.

The burden of bacteremic and non-bacteremic Gram-negative infections: A prospective multicenter cohort study in a low-resistance country.

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands. Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance. Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 - 89) and 86 (95% CI 72-100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102-1,954) for bacteremic and 982 (95% CI 688 - 1,276) for non-bacteremic GNI. Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI.

Associations between common respiratory viruses and invasive group A streptococcal infection: A time-series analysis.

BACKGROUND: Invasive infections by group A Streptococcus (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.