Optimizing Antibiotic Prescribing for Acute Respiratory Tract Infections in German Primary Care: Results of the Regional Intervention Study CHANGE-3 and the Nested cRCT.

Within primary care, acute respiratory tract infections (ARTIs) are the most common reason for prescribing antibiotics. The aim of the CHANGE-3 study was to investigate how antibiotic prescribing for non-complicated ARTIs can be reduced to a reasonable level. The trial was conducted as a prospective study consisting of a regional public awareness intervention in two regions of Germany and a nested cluster randomised controlled trial (cRCT) of a complex implementation strategy. The study involved 114 primary care practices and comprised an intervention period of six winter months for the nested cRCT and two times six winter months for the regional intervention. The primary outcome was the percentage of antibiotic prescribing for ARTIs between baseline and the two following winter seasons. The regression analysis confirmed a general trend toward the restrained use of antibiotics in German primary care. This trend was found in both groups of the cRCT without significant differences between groups. At the same time, antibiotic prescribing was higher in routine care (with the public campaign only) than in both groups of the cRCT. With regard to secondary outcomes, in the nested cRCT, the prescribing of quinolones was reduced, and the proportion of guideline-recommended antibiotics increased.

[Acute respiratory tract infections and antibiotic prescriptions: What are patients' expectations?] / Akute Atemwegsinfekte und Antibiotikaverordnungen: Welche Erwartungen haben Patient*innen?

INTRODUCTION: The use of antibiotics in human medicine is partly responsible for the global increase in antibiotic resistance. Significant reductions in antibiotic prescribing were realised through educational campaigns, communication training and prescribing feedback. Based on data from the cluster-randomised CHANGE-3 trial, the present analysis focuses on the question of patient expectations for an antibiotic in acute respiratory infections. METHODS: 106 of 114 General Practitioner (GP) practices in Baden-Württemberg and Mecklenburg-Western Pomerania took part in the study. 4736 patients who visited the practices with acute respiratory infections from October 2018 to May 2019 filled out a questionnaire after the doctor's consultation. The analysis was descriptive. RESULTS: 16.7 % of patients with acute respiratory infections reported receiving antibiotics from their GP. 13.3 % of patients had hoped for an antibiotic and 5.5 % stated that they had asked their GP for an antibiotic prescription. The lowest prescription rate for antibiotics was reported by patients who had received a diagnosis of influenza from their GP. With specific diagnoses differentiated from uncomplicated respiratory tract infection, an increase in both the number of antibiotics hoped for and the number of antibiotics prescribed was observed. DISCUSSION: Patients still receive antibiotics more often than they actually hope for. On the part of GPs, prescriptions may still be written because of perceived pressure from patients, but this is not reflected in patient expectations. In addition to dealing openly with patients' expectations, strengthening patients' health literacy, mindful doctor-patient communication and offered opportunities for re-presentation in the case of specific diagnoses could further reduce the perceived pressure on GPs.

[Acute respiratory tract infections and antibiotic prescriptions: What are patients' expectations?] / Akute Atemwegsinfekte und Antibiotika-Verordnungen: Welche Erwartungen haben Patient*innen?

INTRODUCTION: The use of antibiotics in human medicine is partly responsible for the global increase in antibiotic resistance. Significant reductions in antibiotic prescribing were realised through educational campaigns, communication training and prescribing feedback. Based on data from the cluster-randomised CHANGE-3 trial, the present analysis focuses on the question of patient expectations for an antibiotic in acute respiratory infections. METHODS: 106 of 114 General Practitioner (GP) practices in Baden-Württemberg and Mecklenburg-Western Pomerania took part in the study. 4736 patients who visited the practices with acute respiratory infections from October 2018 to May 2019 filled out a questionnaire after the doctor's consultation. The analysis was descriptive. RESULTS: 16.7 % of patients with acute respiratory infections reported receiving antibiotics from their GP. 13.3 % of patients had hoped for an antibiotic and 5.5 % stated that they had asked their GP for an antibiotic prescription. The lowest prescription rate for antibiotics was reported by patients who had received a diagnosis of influenza from their GP. With specific diagnoses differentiated from uncomplicated respiratory tract infection, an increase in both the number of antibiotics hoped for and the number of antibiotics prescribed was observed. DISCUSSION: Patients still receive antibiotics more often than they actually hope for. On the part of GPs, prescriptions may still be written because of perceived pressure from patients, but this is not reflected in patient expectations. In addition to dealing openly with patients' expectations, strengthening patients' health literacy, mindful doctor-patient communication and offered opportunities for re-presentation in the case of specific diagnoses could further reduce the perceived pressure on GPs.

Converting habits of antibiotic use for respiratory tract infections in German primary care - study protocol of the cluster-randomized controlled CHANGE-3 trial.

BACKGROUND: The overuse of antibiotics is a major cause for the worldwide rise of antibiotic resistance. Although it is well known that acute respiratory tract infections (ARTI) are mainly caused by viruses and are often self limiting, antibiotics are too frequently prescribed in primary care. CHANGE-3 examines whether a complex intervention focusing on improving communication and provision of prescribing feedback reduces antibiotic use in patients suffering from ARTI. METHODS/DESIGN: The CHANGE-3 trial is a cluster-randomized controlled trial nested within a web-based public campaign conducted in two regions in Germany. A total of 114 medical practices will be included. Practices randomized to the intervention will receive a practice-specific antibiotic-prescription feedback and an educational outreach visit. During the visit the whole practice team will receive an introduction to e-learning modules addressing patient-centered communication on antibiotics. Furthermore, the practices will receive tablet PCs with information on antibiotics and the treatment of ARTI to be presented to patients. Practices randomized to the control will provide care as usual. The primary outcome measure is the antibiotic prescribing rate for patients with a history of ARTI. Data collected before the intervention, during the intervention and after the intervention will be compared. The use of narrow- vs. broad-spectrum antibiotics will be analyzed as a secondary outcome. A process evaluation is also part of the trial. DISCUSSION: This study should contribute to the growing body of research on reducing antibiotic prescription. TRIAL REGISTRATION: ISRCTN, ISRCTN15061174 . Registered retrospectively on 13 July 2018.

Imbalance of dendritic cell co-stimulation in COPD.

BACKGROUND: Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown. METHODS: Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers. RESULTS: Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD. CONCLUSION: An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.

Impact of smoking on dendritic cell phenotypes in the airway lumen of patients with COPD.

BACKGROUND: Myeloid dendritic cells (DCs) are increased in the airway wall of patients with chronic obstructive pulmonary disease (COPD), and postulated to play a crucial role in COPD. However, DC phenotypes in COPD are poorly understood. METHODS: Function-associated surface molecules on bronchoalveolar lavage fluid (BALF) DCs were analyzed using flow cytometry in current smokers with COPD, in former smokers with COPD and in never-smoking controls. RESULTS: Myeloid DCs of current smokers with COPD displayed a significantly increased expression of receptors for antigen recognition such as BDCA-1 or Langerin, as compared with never-smoking controls. In contrast, former smokers with COPD displayed a significantly decreased expression of these receptors, as compared with never-smoking controls. A significantly reduced expression of the maturation marker CD83 on myeloid DCs was found in current smokers with COPD, but not in former smokers with COPD. The chemokine receptor CCR5 on myeloid DCs, which is also important for the uptake and procession of microbial antigens, was strongly reduced in all patients with COPD, independently of the smoking status. CONCLUSION: COPD is characterized by a strongly reduced CCR5 expression on myeloid DCs in the airway lumen, which might hamper DC interactions with microbial antigens. Further studies are needed to better understand the role of CCR5 in the pathophysiology and microbiology of COPD.

Fluticasone impact on airway dendritic cells in smokers: a randomized controlled trial.

BACKGROUND: Myeloid Dendritic cells are key drivers of inflammation in smoke-related lung diseases, whereas plasmacytoid DCs play a crucial role in the defense against infections. Effects of inhaled corticosteroids (ICS) on airway DCs in smokers are unknown. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 45 active cigarette smokers inhaled placebo, fluticasone or fluticasone plus salmeterol twice daily for 4 weeks. Bronchoalveolar lavage fluid DCs were analyzed using four-color flow cytometry before and after the inhalation period. In addition, fluticasone effects were tested on T-cell proliferation in co-cultures with blood myeloid DCs from smokers. RESULTS: Inhalation of fluticasone plus salmeterol, but not fluticasone alone or placebo, reduced endobronchial concentrations of myeloid DCs (median decrease: 24%), macrophages (median decrease: 26%) and neutrophils (median decrease: 76%). In contrast, fluticasone reduced plasmacytoid DC concentrations independently of salmeterol. There were no changes in the expression of function-associated surface molecules on myeloid DC (such as CD1a, Langerin, BDCA-1, CD83 or CCR5) in all groups after treatment. Fluticasone (either alone or in combination with salmeterol) suppressed T-cell proliferation in co-cultures with blood myeloid DCs from smokers. CONCLUSIONS: Resistance to ICS monotherapy in smokers might in part be due to lacking effects on airway myeloid DCs, whereas the increased risk for infections during ICS therapy could be attributable to a reduction in plasmacytoid DCs. Combination therapy of fluticasone with salmeterol is associated with a reduction in airway myeloid DCs, but also airway macrophages and neutrophils. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (identifier: NCT00908362) and the European Clinical Trial Database, EudraCT (identifier: 2009-009459-40).

Plasmacytoid dendritic cells and their Toll-like receptor 9 expression selectively decrease with age.

Dendritic cells (DCs) play a crucial role in the initiation of immune responses against infectious particles and tumor cells; however, the impact of age, anthropometric parameters, and gender on the number and the expression of function-associated molecules of human DCs is poorly understood. In this study, blood DCs of 50 volunteers (19-84 years old) with no acute or chronic inflammatory diseases were examined using 4-color flow cytometry. Increasing age was associated with a decrease in blood plasmacytoid, but not myeloid DCs and a selective decrease in Toll-like receptor 9 (TLR9) expression by plasmacytoid DCs. In contrast, gender and body mass index did not impact the number of DC subsets or the expression of function-associated DC molecules. Thus, we demonstrate that age has a selective impact on plasmacytoid DCs and their TLR9 expression. This may contribute to an increased susceptibility to infections and tumors with increasing age.