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Background: The Dutch Working Party on Antibiotic Policy is developing a national antimicrobial stewardship registry. This registry will report both the quality of antibiotic use in hospitals in the Netherlands and the stewardship activities employed. It is currently unclear which aspects of the quality of antibiotic use are monitored by antimicrobial stewardship teams (A-teams) and can be used as indicators for the stewardship registry. In this pilot study we aimed to determine which stewardship objectives are eligible for the envisioned registry.Methods: We performed an observational pilot study among five Dutch hospitals. We assessed which of the 14 validated stewardship objectives (11 process of care recommendations and 3 structure of care recommendations) the A-teams monitored and documented in individual patients. They provided, where possible, data to compute quality indicator (QI) performance scores in line with recently developed QIs to measure appropriate antibiotic use in hospitalized adults for the period of January 2015 through December 2015 RESULTS: All hospitals had a local antibiotic guideline describing recommended antimicrobial use. All A-teams monitored the performance of bedside consultations in Staphylococcus aureus bacteremia and the prescription of restricted antimicrobials. Documentation and reporting were the best for the use of restricted antimicrobials: 80% of the A-teams could report data. Lack of time and the absence of an electronic medical record system enabling documentation during the daily work flow were the main barriers hindering documentation and reporting.Conclusions: Five out of 11 stewardship objectives were actively monitored by A-teams. Without extra effort, 4 A-teams could report on the quality of use of restricted antibiotics. Therefore, this aspect of antibiotic use should be the starting point of the national antimicrobial stewardship registry. Our registry is expected to become a powerful tool to evaluate progress and impact of antimicrobial stewardship programs in hospitals. [ABSTRACT FROM AUTHOR]

The article presents a comparison of national antimicrobial guide, SWAB-ID based and non-SWAB-ID based. It was in 2006 when the Dutch Working Party on Antibiotic Policy (SWAB) developed an online national antimicrobial guide for treatment of infectious diseases. The Netherland's adoption of this guide is discussed.

Background: After antibiotic treatment of Lyme borreliosis, a subset of patients report persistent symptoms, also referred to as post-treatment Lyme disease syndrome. The reported prevalence of persistent symptoms varies considerably, and its pathophysiology is under debate. The LymeProspect study has been designed to investigate the prevalence, severity, and a wide range of hypotheses on the etiology of persistent symptoms among patients treated for Lyme borreliosis in the Netherlands.Methods: LymeProspect is a prospective, observational cohort study among adults with proven or probable Lyme borreliosis, either erythema migrans or disseminated manifestations, included at the start of antibiotic treatment. During one year of follow-up, participants are subjected to questionnaires every three months and blood is collected repeatedly during the first three months. The primary outcome is the prevalence of persistent symptoms after treatment, assessed by questionnaires online focusing on fatigue (CIS, subscale fatigue severity), pain (SF-36, subscale pain) and neurocognitive dysfunction (CFQ). Potential microbiological, immunological, genetic, epidemiological and cognitive-behavioral determinants for persistent symptoms are secondary outcome measures. Control cohorts include patients with long-lasting symptoms and unconfirmed Lyme disease, population controls, and subjects having reported a tick bite not followed by Lyme borreliosis.Discussion: This article describes the background and design of the LymeProspect study protocol. This study is characterized by a prospective, explorative and multifaceted design. The results of this study will provide insights into the prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis, and may provide a rationale for preventive and treatment recommendations.Trial Registration: NTR4998 (Netherlands Trial Register). Date of registration: 13 February 2015. [ABSTRACT FROM AUTHOR]

Background: In 2004, the Surviving Sepsis Campaign (SSC), a global initiative to reduce mortality from sepsis, was launched. Although the SSC supplies tools to measure and improve the quality of care for patients with sepsis, effective implementation remains troublesome and no recommendations concerning the role of nurses are given. Objectives: To determine the effects of a multifaceted implementation program including the introduction of a nurse-driven, care bundle based, sepsis protocol followed by training and performance feedback. Design and setting: A prospective before-and-after intervention study conducted in the emergency department (ED) of a university hospital in the Netherlands. Participants: Adult patients (≥16 years old) visiting the ED because of a known or suspected infection to whom two or more of the extended systemic inflammatory response syndrome (SIRS) criteria apply. Methods: We measured compliance with six bundled SSC recommendations for early recognition and treatment of patients with sepsis: measure serum lactate within 6h, obtain two blood cultures before starting antibiotics, take a chest radiograph, take urine for urinalysis and culture, start antibiotics within 3h, and hospitalize or discharge the patient within 3h. Results: A total of 825 patients were included in the study. Compliance with the complete bundle significantly improved from 3.5% at baseline to 12.4% after our entire implementation program was put in place. The completion of four of six individual elements improved significantly, namely: measure serum lactate (improved from 23% to 80%), take a chest radiograph (from 67% to 83%), take urine for urinalysis and culture (from 49% to 67%), and start antibiotics within 3h (from 38% to 56%). The mean number of performed bundle elements improved significantly from 3.0 elements at baseline to 4.2 elements after intervention [1.2; 95% confidence interval=0.9–1.5]. Conclusions: Early recognition of sepsis in patients presenting to the ED and compliance with SSC recommendations significantly improved after the introduction of a predominantly nurse-driven, care bundle based, sepsis protocol followed by training and performance feedback. [Copyright &y& Elsevier]

Background: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology., Methods: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice)., Findings: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms., Interpretation: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated., Funding: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS)., Competing Interests: Declaration of interests MEB, FRvdS and JWH report collaborations on LB diagnostics with Pfizer, Antigen Discovery Inc., Oxford Immunotec, AID/GenID, and InVitaLab; funding to institution and/or material supplied for research free of charge, no personal financial compensation. MEB reports support for travel expenses related to LB symposium at Massachusetts General Hospital. LABJ and BJK are co-inventor of Spirofind, an experimental in-house assay for Lyme borreliosis, which is owned by Radboudumc and will not be developed further as potential diagnostic test. CCvdW is a consortium partner and partner in sub-project in the NMCB consortium (The Dutch ME/CFS Cohort and Biobank Consortium) funded by Netherlands Organization for Health Research and Development (ZonMw, project numbers 10091012110027 and 10091012110018). The other authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Current outpatient parenteral antimicrobial therapy (OPAT) guidelines recommend delivering patient-centred care. However, little is known about what patients define as good quality of OPAT care and what their needs and preferences are.The aim of this qualitative study is to explore the patients' perspective on high-quality care, and to explore what patient-centred care means to adult OPAT patients., Design and Setting: This is an explorative, descriptive study using qualitative methods. We conducted focus group interviews with 16 adult patients (5 female, 11 male) from 3 different hospitals, who received OPAT and 2 individual semistructured interviews with their informal caregivers in the Netherlands. We used purposive sampling to ensure diversity of participants. We used the eight Picker principles of patient-centredness to guide data collection and analysis., Results: Participants reported several elements considered as important for patient-centred OPAT care, like patient involvement in the decision-making process, a responsible OPAT lead, intensive collaboration between all disciplines involved, information provision and adherence to hygiene guidelines. Two central dimensions emerged as essential constituents of patient-centred OPAT care: freedom and safety. Both are heavily influenced by the behaviours of healthcare professionals and by organisational aspects beyond the direct influence of these professionals., Conclusion: This study provides insights into the needs and preferences of adult patients who receive OPAT care. Future interventions directed at the improvement of patient-centredness of OPAT care should focus on elements that enhance patients' feelings of freedom and safety., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1-/- mice uniformly succumbed to Candida-induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1-/- mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1-mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis.

Background: Dectin-1 is the major receptor for fungal β-glucans on myeloid cells. We investigated whether defective Dectin-1 receptor function, because of the early stop codon polymorphism Y238X, enhances susceptibility to invasive aspergillosis (IA) in at-risk patients., Methods: Association of Dectin-1 Y238X polymorphism with occurrence and clinical course of IA was evaluated in 71 patients who developed IA post hematopoietic stem cell transplantation (HSCT) and in another 21 non-HSCT patients with IA. The control group consisted of 108 patients who underwent HSCT. Functional studies were performed to investigate consequences of the Y238X Dectin-1 polymorphism., Results: The Y238X allele frequency was higher in non-HSCT patients with IA (19.0% vs 6.9%-7.7%; P < .05). Heterozygosity for Y238X polymorphism in HSCT recipients showed a trend toward IA susceptibility (odds ratio, 1.79; 95% CI, .77-4.19; P = .17) but did not influence clinical course of IA. Functional assays revealed that although peripheral blood mononuclear cells with defective Dectin-1 function due to Y238X responded less efficiently to Aspergillus, corresponding macrophages showed adequate response to Aspergillus., Conclusions: Dectin-1 Y238X heterozygosity has a limited influence on susceptibility to IA and may be important in susceptible non-HSCT patients. This is partly attributable to redundancy inherent in the innate immune system. Larger studies are needed to confirm these findings.

Background: Limited data exist on the most effective approach to increase the quality of antibiotic use for lower respiratory tract infections at hospitals., Methods: One thousand nine hundred six patients with community-acquired pneumonia or an exacerbation of chronic obstructive pulmonary disease (acute exacerbation of chronic bronchitis) were included in a cluster-randomized, controlled trial at 6 medium-to-large Dutch hospitals. A multifaceted guideline-implementation strategy that was tailored to baseline performance and considered the barriers in the target group was used. Principal outcome measures were (1) guideline-adherent antibiotic prescription, (2) adaptation of dose and dose interval of antibiotics according to renal function, (3) switches in therapy, (4) streamlining of therapy, and (5) Gram staining and culture of sputum samples. Secondary process outcomes were applicable to community-acquired pneumonia (e.g., timely administration of antibiotics) or acute exacerbation of chronic bronchitis (e.g., not prescribing macrolides)., Results: The rate of guideline-adherent antibiotic prescription increased from 50.3% to 64.3% in the intervention hospitals (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.57-4.42; P=.0008). The rate of adaptation of antibiotic dose according to renal function increased from 79.4% to 95.1% in the intervention hospitals (OR, 7.32; 95% CI, 2.09-25.7; P=.02). The switch from intravenous to oral therapy improved more in the control hospitals (from 53.3% to 71.9%) than in the intervention hospitals (from 74% to 83.6%). The change from broad-spectrum empirical therapy to pathogen-directed therapy improved by 5.7% in the intervention hospitals (P = not significant). Fewer sputum samples were obtained from both the intervention group (rate of sputum samples obtained decreased from 55.8% to 53.1%) and the control group (rate of sputum samples obtained decreased from 49.6% to 42.7%). Timely administration of antibiotics for community-acquired pneumonia increased significantly in the intervention group (from 55.2% to 62.9%; OR, 2.49; 95% CI, 1.11-5.57; P=.026)., Conclusions: With regard to some important aspects, tailoring interventions to change antibiotic use improved the quality of treatment for patients hospitalized with lower respiratory tract infection.

Objectives: Misuse of antibiotics in surgical prophylaxis is still quite common. The objectives of this study were to reduce the quantity and improve the quality of surgical prophylaxis and to reduce costs., Methods: Prospective multi-site study of elective procedures in 13 Dutch hospitals. The quality of prophylaxis was audited before and after an intervention consisting of performance feedback and implementation of national clinical practice guidelines. Process outcome parameters were antibiotic choice, duration, timing, antibiotic volume and costs. Segmented regression analysis was used to estimate the effect size of the intervention. Patient outcome was documented by the incidence of surgical site infections (SSI)., Results: Before the intervention, 1763 procedures were recorded and 2050 thereafter. Antimicrobial use decreased from 121 to 79 DDD (defined daily doses)/100 procedures and costs reduced by 25% per procedure. After the intervention, antibiotic choice was inappropriate in only 37.5% of the cases instead of in 93.5% expected cases had the intervention not occurred. Prolonged prophylaxis was observed in 31.4% instead of 46.8% expected cases and inappropriate timing in 39.4% instead of the expected 51.8%. Time series analysis showed that all improvements were statistically significant (P < 0.01) and that they could be fully attributed to the intervention. The overall SSI rates before and after intervention were 5.4% (95% CI: 4.3-6.5) and 4.6% (95% CI: 3.6-5.4), respectively., Conclusions: The intervention led to improved quality of surgical prophylaxis and to reduced antibiotic use and costs without impairment of patient outcome.

Objectives: To develop effective and targeted interventions to improve care for patients with community-acquired pneumonia (CAP), insight is needed into the factors that influence the quality of antibiotic use. Therefore, we measured the performance of nine quality indicators and studied determinants of variation in the quality of antibiotic use., Patients and Methods: Data on 498 prospectively included patients with CAP from eight medium-sized Dutch hospitals were extracted from the medical charts. Outcomes of nine indicators were calculated using previously constructed algorithms. Multilevel logistic regression analysis was performed to explain differences in performance rates at the patient, doctor and hospital level., Results: Performance indicators were generally moderate. Markers of severe illness were found to be positive predictors of timely administration of antibiotics (low oxygen saturation on admission OR 1.11; 95% CI: 1.04--1.19) and obtaining blood samples for culture (low sodium concentration on admission OR 1.10; 95% CI: 1.03--1.16). Recent outpatient antibiotic therapy (OR 0.46; 95% CI: 0.26--0.80) and presence of a hospital antibiotic committee (OR 0.27; 95% CI: 0.08--0.90) were negatively associated with guideline-adherent empirical therapy. The main positive predictor of timely administration of antibiotics (within 4 h) was antibiotic administration in the Emergency Department (ED) (OR 3.9; 95% CI: 1.96--8.73)., Conclusions: We gained new insights into factors that determine quality of antibiotic prescription in hospitals. Treatment in the ED, rather than in the ward, will result in earlier administration of antibiotics. Guidelines should clarify preferred antibiotic management of patients who have received antibiotics prior to admission. Hospital-based structures aimed at quality improvement, such as antibiotic committees, do not necessarily lead to better adherence to national standards. Efforts should be made to encourage these committees to implement national guidelines at a local level.

Background: Timely administration of the first dose, dosage adjustment to renal function, switch from intravenous to oral administration, and streamlining are important aspects of rational antibiotic prescription. The goals of this study were to investigate all of these variables, compare them with predefined quality standards, and implement improvement with specific interventions., Methods: At the departments of internal medicine, surgery, and neurology and the emergency department of a tertiary referral university medical center, all consecutive patients receiving therapeutic antibiotics were enrolled. Dosages, timing of first doses, dosing intervals, administration routes, and adjustment of the chosen drug to clinical data were investigated. After the preintervention period, barriers to change were identified, followed by specific interventions and a postintervention measurement., Results: In the preintervention and postintervention periods, 247 and 250 patients were enrolled, receiving 563 and 598 antibiotic prescriptions, respectively. The mean time from the order to first dose at the wards improved from 2.7 to 1.7 hours in potentially severe cases (P =.003). Dosage adjustment to renal function remained unchanged at 45% vs 52% (P =.09) of cases where necessary. Switching of therapy from intravenous to oral improved from 46% to 62% (P =.03) and was performed a mean of 1.6 days earlier (P =.002). Streamlining was performed correctly in most cases, and thus no interventions were necessary., Conclusions: Timing of antibiotic therapy and switch therapy may be improved with a combination of interventions. To improve poor adjustment of dosing to renal function, other strategies are needed. In our setting, streamlining was already correct in most cases.