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Background: The clinical frailty scale (CFS) was used as a triage tool for medical decision making during the COVID-19 pandemic. The CFS has been posed as a suitable risk marker for in-hospital mortality in COVID-19 patients. We evaluated whether the CFS is associated with mortality 24 months after hospitalisation for COVID-19. Methods: The COvid MEdicaTion (COMET) study is an international, multicentre, observational cohort study, including adult patients hospitalised for COVID-19 between March 2020–July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected at admission, survival data were collected 24 months after hospitalisation. Multivariable cox proportional hazard models stratified by age (

Objectives: The COVID-19 pandemic highlights the importance of understanding facilitators for disease transmission. Events such as Carnival, characterized by large gatherings and extensive social interactions, have the potential to become ‘super spreading events' for respiratory infections. This paper aims to assess the impact of large gatherings on virus transmission, providing crucial insights for the development of effective public health strategies. Study design: An ecological study was performed. Methods: The age-standardized number of COVID-19 cases reported in 2022, stratified by age (under 60 and 60+ years) was compared countrywide for Dutch provinces where Carnival was celebrated versus those where it was not. Additionally, we compared standardized hospitalization rates in 2022 and 2023 for both areas. Results: Countrywide, 2,278,431 COVID-19 cases were reported between 06-02-2022 and 10-04-2022. Daily incidence increased after Carnival, peaking at 803 per 100,000 inhabitants for under 60s in carnival provinces and 368 in non-carnival provinces. For individuals 60+ daily incidence peaked at 396 in carnival provinces and 247 in non-carnival provinces. Over the 10 weeks following the start of Carnival, the carnival provinces demonstrated a 15 % (2022) 17 % (2023) higher hospitalization rate compared to non-carnival provinces. Conclusions: The peak in cases and hospitalizations in regions actively celebrating Carnival compared to the rest of the Netherlands qualifies Carnival as a ‘super-spreading’ event. Our findings underscore the elevated risk of respiratory infections associated with large gatherings, advocating guided policies, including transparent risk communication and healthcare preparedness.

We describe vaginal microbiota, including Gardnerella species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB

Summary: Two SARS-CoV-2 nosocomial outbreaks occurred on the haematology ward of our hospital. Patients on the ward were at high risk for severe infection because of their immunocompromised status. Whole Genome Sequencing proved transmission of a particular SARS-CoV-2 variant in each outbreak. The first outbreak (20 patients/31 healthcare workers (HCW)) occurred in November 2020 and was caused by a variant belonging to lineage B.1.221. At that time, there were still uncertainties on mode of transmission of SARS-CoV-2, and vaccines nor therapy were available. Despite HCW wearing II-R masks in all patient contacts and FFP-2 masks during aerosol generating procedures (AGP), the outbreak continued. Therefore, extra measures were introduced. Firstly, regular PCR-screening of asymptomatic patients and HCW; positive patients were isolated and positive HCW were excluded from work as a rule and they were only allowed to resume their work if a follow-up PCR CT-value was ≥30 and were asymptomatic or having only mild symptoms. Secondly, the use of FFP-2 masks was expanded to some long-lasting, close-contact, non-AGPs. After implementing these measures, the incidence of new cases declined gradually. Thirty-seven percent of patients died due to COVID-19.The second outbreak (10 patients/2 HCW) was caused by the highly transmissible omicron BA.1 variant and occurred in February 2022, where transmission occurred on shared rooms despite the extra infection control measures. It was controlled much faster, and the clinical impact was low as the majority of patients was vaccinated; no patients died and symptoms were relatively mild in both patients and HCW.

Introduction: Higher antibody levels, in particular antibodies directed against the receptor-binding domain (RBD) of the spike protein, protect against re-infection with SARS-CoV-2. Quantitative antibody response data provide insight into population immunity and are essential for decision-making on booster-vaccination strategies. We aimed to identify predictors for higher antibody responses such as gender, age, experienced COVID-19-compatible symptoms, disease severity and exposure to pre-determined risk factors associated with SARS-CoV-2 seropositivity. Materials and methods: Quantitative anti-S-RBD responses were analysed in seropositive vaccine-naive individuals (n = 1,857) from a study population of 10,001 adults, including healthcare workers (n = 211) and individuals with a known date of a positive PCR (n = 214). Regression models tested associations between age, gender, the period of symptoms, disease severity, pre-identified exposure factors associated with SARS-CoV-2 seropositivity, and anti-S-RBD responses. Results: Symptoms of more severe disease (fever and/or dyspnoea: OR 2.42 [95%CI 1.76–3.34], and hospital admission: OR 11.41 [95%CI 4.66–27.97]), and a longer interval between COVID-19-compatible symptoms and serum collection (OR 3.17 [95%CI 1.32–7.63]) were predictive for anti-S-RBD levels ≥300 U/mL. Working in healthcare was inversely associated with anti-S-RBD levels ≥300 U/mL (OR 0.51 [95%CI 0.31–0.82]). None of the pre-identified exposure factors associated with SARS-CoV-2 seropositivity could be identified as predictive of higher anti-S-RBD responses. Conclusion: No exposure factors were identified as predictors of higher neutralising antibody responses. Nevertheless, higher neutralising antibody levels in individuals with more severe symptoms suggest better immunological protection against SARS-CoV-2 re-infection. In seroprevalence studies, that mainly include asymptomatic or mildly infected individuals, the determination of quantitative antibody responses may help in the interpretation of population immunity.

COVID-19 booster vaccination has shown to add to the protection against infection with SARS-CoV2 and subsequent severe disease. This longitudinal cross-border study aimed to identify factors associated with COVID-19 booster vaccine intentions in an initially vaccinated adult population living in the Meuse-Rhine Euroregion (EMR; including the Netherlands, Belgium, and Germany) and differences between countries.Data collection took place in autumn of 2021 and consisted of online questionnaires sent to a random sample of the population based on governmental registries. Data from 3,319 fully and partially vaccinated adults were used to examine determinants of non-positive intention for a booster vaccination (i.e., uncertain or do not want), using multivariable logistic regression analyses weighted by age group, sex, and country.Compared to German residents, Dutch residents (OR = 2.4) and Belgian residents (OR = 1.4) were more likely to be uncertain or not want to receive a booster vaccine in September-October 2021. Factors independently associated with non-positive intention were female sex (OR = 1.6), absence of comorbidities (OR = 1.3), time since last vaccination less than 3 months ago for those fully vaccinated (OR = 1.6), being partially vaccinated (OR = 3.6), a negative experience with communication of COVID-19 measures (OR = 2.2), and regarding measures as ineffective (OR = 1.1).Results indicate that booster vaccine intentions differ between countries in the cross border Meuse-Rhine Euroregion. Non-positive intention for the booster vaccine is prevalent in all three countries of the EMR, but to a different extent, as shown in this study. Cross-border collaboration and sharing information and knowledge about vaccination strategies could play a role in limiting the impact of COVID-19.

Presently, many studies assess allergenicity via IgE immunoblotting and IgE binding tests; however, IgE detection does not always signal the manifestation of a clinical allergy. However, the capacity of food allergens to trigger basophils makes it possible to use the in vitro functional basophil activation test (BAT) to assess allergenicity. The effect of the Maillard reaction (MR) on the allergenic potential of processed soy proteins was evaluated by two IgE binding tests (Competitive ELISA and Inhibition ImmunoCAP), a Western Blot and a functional BAT; with the aim to analyze whether the sIgE binding results correspond to the functional assay results. The results between the IgE binding tests and the functional assay were in-line for 2 of the 6 studied patients. For one patient there was no correlation between any of the results. For the raw soy protein extract heated with glucose for 10 and 30 min (SH SPE + Glu and LH SPE + Glu, respectively), the results were in-line for only 3 out of the 6 patients. Thus, the present study shows a discrepancy between IgE binding tests and basophil stimulation when assessing the effect of soy processing on its allergenicity. Since IgE-binding capacity does not always correlate to IgE cross-linking capacity, the conclusions of the allergenic potential based on the IgE binding tests alone should be drawn with care and further studies on this matter would benefit from the inclusion of a functional assay such as the BAT.

Objectives: To evaluate the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on immune, oxidative stress and neurochemical biomarkers in paediatric Attention-Deficit Hyperactivity Disorder (ADHD) as compared to methylphenidate (MPH) and placebo. Results: Paediatric ADHD patients (n = 88, 70 % male, mean age 10.1 years) were randomised (placebo (n = 30), PBE (n = 32) and MPH (n = 26)) receiving 20 mg/day if

Objectives: Determine the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on Attention-Deficit Hyperactivity Disorder (ADHD) behaviour and co-morbid physical/psychiatric symptoms, compared to placebo and the medicine MPH, and to assess its tolerability. Behaviour (measured by the ADHD-Rating Scale (ADHD-RS) and Social-Emotional Questionnaire (SEQ)) and physical complaints were evaluated in weeks 5 and 10. Results: Eighty-eight paediatric ADHD patients (70 % male, mean age 10.1 years) were randomised to placebo (n = 30), PBE (n = 32) or MPH (n = 26). Teachers reported significant improvement of total and hyperactivity/impulsivity ADHD-RS scores by PBE and MPH after 10 weeks compared to placebo. MPH also improved inattention. SEQ ratings support ADHD-RS results. Adverse effects were reported five times more frequently for MPH than for PBE. Conclusions: PBE appears a good alternative for MPH in paediatric ADHD and especially in the primary school environment, a fortiori when considering its almost complete lack of adverse effects.

Summary: In 2019–2020, two subsequent outbreaks caused by phenotypically identical ESBL-producing Enterobacter cloacae and multi-drug-resistant (MDR) Pseudomonas putida were detected in respectively 15 and 9 patients of the haematology-oncology department. Both bacterial species were resistant to piperacillin-tazobactam, used empirically in (neutropenic) sepsis in our hospital, and ciprofloxacin, used prophylactically in selective digestive decontamination for haematology patients. The E. cloacae outbreak was identified in clinical cultures of blood and urine. Despite intensified infection control measures, new cases were found in weekly point-prevalence screening cultures. Environmental samples of sinks and shower drains appeared positive in 18.1%. To diminish the environmental contamination burden, all siphons of sinks were replaced, and disinfection of sinks and shower drains was intensified using chlorine and soda on a daily basis. Replacement of shower drains was not possible. The outbreak of P. putida remained limited to rectal cultures only, and disappeared spontaneously without interventions. During both outbreaks, multiple strains of the incriminated bacterium were found simultaneously (demonstrated by Amplified-Fragment Length Polymorphism and/or Whole-Genome Multi-locus Sequencing Typing) in patients as well as the environment. It was experimentally shown that a biofilm on the toilet edge may act as a source for nosocomial transmission of Gram-negative bacteria. In conclusion, the drainage system of the hospital is an important reservoir of MDR bacteria, threatening the admitted patients. In existing hospitals, biofilms in the drainage systems cannot be removed. Therefore, it is important that in (re)building plans for hospitals a plan for prevention of nosocomial transmission from environment to patients is incorporated.

Introduction: There is a need for detailed data on early antibody responses against SARS-CoV-2 as this may contribute to the prediction of the clinical course of COVID-19 and the optimization of convalescent plasma treatment. This study aims to gain insight into developing antibodies to SARS-CoV-2 in health care workers (HCWs) infected in the first wave of the SARS-CoV-2 pandemic in the Netherlands. Materials and methods: In this retrospective analysis, sera from PCR-confirmed COVID-19 positive HCWs are included at the time of the initial PCR (T = 0, n = 95) and at least 21 days after the initial serum (T ≥ 21, n = 133). This study assesses correlations between qualitative total Ig, IgM, IgA, IgG, and quantitative anti-S-RBD antibody responses and participant characteristics. Results: Higher Ct values were associated with higher antibody positivity rates for total Ig (OR 1.261 (95% CI 1.095–1.452)), IgM (OR 1.373 (95% CI 1.125–1.675)), and IgA (OR 1.222 (95% CI 1.013–1.475)). Gender was predictive of IgM and IgA antibody positivity rates at T = 0 (OR 0.018 (95% CI 0.001–0.268)) and (OR 0.070 (95% CI 0.008–0.646)). At T ≥ 21, a substantial proportion of HCWs developed IgM (103/133; 77.4%) and total Ig (128/133; 96.2%) antibodies. IgA and IgG seroconversions were observed in only 51.1% (67/131) and 55.7% (73/131) of HCWs. Anti-S-RBD responses were higher when the interval between onset of symptoms and sampling was longer. Conclusion: The findings of this study give insight into early antibody responses and may have implications for the selection of convalescent plasma donors and the further development of monoclonal antibody treatment.

Objectives: To determine the effect of a single dose of gentamicin on the incidence and persistence of acute kidney injury (AKI) in patients with sepsis in the emergency department (ED)., Methods: We retrospectively studied patients with sepsis in the ED in three hospitals. Local antibiotic guidelines recommended a single dose of gentamicin as part of empirical therapy in selected patients in one hospital, whereas the other two hospitals did not. Multivariate analysis was used to evaluate the effect of gentamicin and other potential risk factors on the incidence and persistence of AKI after admission. AKI was defined according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria., Results: Of 1573 patients, 571 (32.9%) received a single dose of gentamicin. At admission, 181 (31.7%) of 571 of the gentamicin-treated and 228 (22.8%) of 1002 of the non-gentamicin-treated patients had AKI (p < 0.001). After admission, AKI occurred in 64 (12.0%) of 571 patients who received gentamicin and in 82 (8.9%) of 1002 people in the control group (p 0.06). Multivariate analysis showed that shock (odds ratio (OR), 2.72; 95% CI, 1.31-5.67), diabetes mellitus (OR, 1.49; 95% CI, 1.001-2.23) and higher baseline (i.e. before admission) serum creatinine levels (OR, 1.007; 95% CI, 1.005-1.009) were associated with the development of AKI after admission, but not receipt of gentamicin (OR, 1.29; 95% CI, 0.89-1.86). Persistent AKI was rare in both the group that received gentamicin (16/260, 6.2%) and the group that did not (15/454, 3.3%, p 0.09)., Conclusions: With regard to renal function, a single dose of gentamicin in patients with sepsis in the ED is safe. The development of AKI after admission was associated with shock, diabetes mellitus and higher baseline creatinine level., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recently, chicken meat was identified as a plausible source of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli in humans. We investigated the relatedness of ESBL-producing Klebsiella spp. in chicken meat and humans. Furthermore, we tested the performance of SpectraCell RA(®) (River Diagnostics), a new typing method based on Raman spectroscopy, in comparison with multilocus sequence typing (MLST) for Klebsiella pneumoniae. Twenty-seven phenotypically and genotypically confirmed ESBL-producing Klebsiella spp. isolates were typed with MLST and SpectraCell RA. The isolates derived from chicken meat, human rectal swabs and clinical blood cultures. In the 22 ESBL-producing K. pneumoniae isolates, CTX-M15 was the predominant genotype, found in five isolates of human origin and in one chicken meat isolate. With MLST, 16 different STs were found, including five new STs. Comparing the results of SpectraCell RA with MLST, we found a sensitivity of 70.0% and a specificity of 81.8% for the new SpectraCell RA typing method. Therefore, we conclude that SpectraCell RA is not a suitable typing method when evaluating relationships of ESBL-producing Klebsiella spp. at the population level. Although no clustering was found with isolates of chicken meat and human origin containing the same ESBL genes, MLST showed no clustering into distinctive clones of isolates from chicken meat and human origin. More studies are needed to elucidate the role of chicken meat in the rise of ESBL-producing Klebsiella spp. in humans., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

The aim of this study was to determine the rate of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in the community in the Netherlands and to gain understanding of the epidemiology of these resistant strains. Faecal samples from 720 consecutive patients presenting to their general practitioner, obtained in May 2010, and between December 2010 and January 2011, were analysed for presence of ESBL-E. Species identification and antibiotic susceptibility testing were performed according to the Dutch national guidelines. PCR, sequencing and microarray were used to characterize the genes encoding for ESBL. Strain typing was performed with amplified fragment length polymorphism (AFLP) and multilocus sequence typing (MLST). Seventy-three of 720 (10.1%) samples yielded ESBL-producing organisms, predominantly E. coli. No carbapenemases were detected. The most frequent ESBL was CTX-M-15 (34/73, 47%). Co-resistance to gentamicin, ciprofloxacin and cotrimoxazole was found in (9/73) 12% of the ESBL-E strains. AFLP did not show any clusters, and MLST revealed that CTX-M-15-producing E. coli belonged to various clonal complexes. Clonal complex ST10 was predominant. This study showed a high prevalence of ESBL-producing Enterobacteriaceae in Dutch primary care patients with presumed gastrointestinal discomfort. Hence, also in the Netherlands, a country with a low rate of consumption of antibiotics in humans, resistance due to the expansion of CTX-M ESBLs, in particular CTX-M-15, is emerging. The majority of ESBL-producing strains do not appear to be related to the international clonal complex ST131., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

The emergence of carbapenem resistance in Pseudomonas aeruginosa threatens the efficacy of this important anti-pseudomonal antibiotic class. Between 2003 and 2006, an increase in the number of carbapenem-resistant P. aeruginosa isolates at the Zonguldak Karaelmas University Hospital was observed (Zonguldak, Turkey). To assess the imipenem resistance mechanisms emerging in these P. aeruginosa isolates, they were characterized by amplified fragment length polymorphism typing, which revealed diversity among imipenem-resistant isolates as well as two clonally related outbreak groups. The molecular mechanism of carbapenem resistance was characterized in a representative isolate from each clonal group. Mutational disruption of oprD was the most frequently encountered resistance mechanism (23/27 isolates)., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

The role of the species Mycobacterium haemophilum as a pathogenic non-tuberculous microorganism is becoming better defined with the use of specific detection methods. However, epidemiological investigations of this species are still scarce. We analysed the genetic diversity of M. haemophilum by amplified fragment length polymorphism (AFLP) typing and compared isolates from different parts of the world. In total, 128 isolates, including 41 from the USA, 51 from Australia, 28 from Europe and eight from Israel were compared using AFLP methodology. Two restriction enzymes (MseI and EcoRI) and one selective primer were applied and provided a high discriminatory power. Clusters of isolates with identical AFLP patterns, which could indicate a possible common source, were observed from the Netherlands, New York and Australia. No clear clustering on the basis of continental origin was observed; however, types were restricted to geographical areas and not found on other continents. A high genetic stability within the species was demonstrated by the long-term existence of a single type.

Mannose-binding lectin (MBL) plays an important role in the innate immune response. Three alleles in the MBL gene, and one allele of the promoter, independently cause low serum MBL levels as compared with the wild-type. This study investigated the relationship between MBL genotype and the occurrence of nosocomial infection among neonates in a neonatal intensive care unit (NICU). Prospectively gathered information concerning nosocomial infection was available for 742 neonates from a recently performed surveillance study in an NICU. DNA was isolated from Guthriecards for a subgroup of 204 neonates who stayed in the NICU for > or =4 days. After a pre-PCR for the MBL gene in blood spots on Guthriecards, mutations were analysed by real-time PCR to detect six mutations in the MBL gene. An MBL genotype could be determined for 186 neonates. As compared to term neonates, genotypes encoding MBL-deficient haplotypes were significantly more prevalent among pre-term neonates. Forty-one of these neonates developed sepsis, with blood cultures yielding coagulase-negative staphylococci in 25 cases. Pneumonia occurred in 30 cases, with various causative organisms. No relationship was found between MBL genotype and the risk of nosocomial sepsis or pneumonia, even after correction for birth-weight, perhaps because of an insufficient correlation between genotype and the concentration of functional MBL. In addition, most bloodstream infections in the NICU were caused by coagulase-negative staphylococci, to which MBL binds poorly.

A significant increase in the isolation frequency of ciprofloxacin-resistant Escherichia coli was observed in the haematology departments of two university hospitals in The Netherlands. Amplified fragment length polymorphism analysis revealed that this increase was not caused by the emergence of unique ciprofloxacin-resistant clones. Determination of the presence of class 1 integrons indicated that 81% of the ciprofloxacin-resistant isolates contained an intI1 gene, compared with 11% of the ciprofloxacin-susceptible isolates (p<0.0001). The quinolone resistance gene qnrA was not present in any of the integrons characterised and could not be detected using dot-blot hybridisation of total DNA. In addition, conjugation experiments showed that ciprofloxacin resistance was not co-transferred with class 1 integrons. Ciprofloxacin-resistant isolates harboured mutations in the gyrA gene, which are known to encode ciprofloxacin resistance. In conclusion, an association was observed between ciprofloxacin resistance and the presence of class 1 integrons, which could not be explained by the currently known genetic determinants of quinolone resistance.