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Background Knowledge about how older adults get a respiratory infection is crucial for planning preventive strategies. We aimed to determine how contact with young children living outside of the household affects the risk of acute respiratory tract infections (ARTI) in community-dwelling older adults. Methods This study is part of the European RESCEU older adult study. Weekly surveillance was performed to detect ARTI throughout 2 winter seasons (2017-2018, 2018-2019). Child exposure, defined as having regular contact with children under 5 living outside of the subject’s household, was assessed at baseline. The average attributable fraction was calculated to determine the fraction of ARTI explained by exposure to these children. Results We prospectively established that 597/1006 (59%) participants experienced at least 1 ARTI. Child exposure increased the risk of all-cause ARTI (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.21 -2.08; P = .001). This risk was highest in those with the most frequent contact (aOR, 1.80; 95% CI, 1.23-2.63; P = .003). The average attributable fraction of child exposure explaining ARTI was 10% (95% CI, 5%-15%). Conclusions One of 10 ARTI in community-dwelling older adults is attributable to exposure to preschool children living outside of the household. Clinical Trials Registration NCT03621930.

Background Respiratory syncytial virus (RSV) surveillance is heavily dependent on the influenza-like illness (ILI) case definition from the World Health Organization (WHO). Because ILI includes fever in its syndromic case definition, its ability to accurately identify acute respiratory tract infections (ARTI) caused by RSV in older adults is uncertain. Methods The accuracy of the WHO ILI and a modified ILI (requiring only self-reported fever) case definitions in identifying patients with PCR-confirmed RSV-ARTI was evaluated in community-dwelling older adults (≥60 years) from the prospective European RESCEU cohort study. Results Among 1040 participants, 750 ARTI episodes were analyzed including 36 confirmed RSV-ARTI. Due to a general lack of fever, sensitivity for RSV-ARTI was 33% for modified ILI and 11% for ILI. The area under the curve for both ILI definitions was 0.52 indicating poor discrimination for RSV. RSV-ARTI could not be distinguished from all other ARTI based on clinical symptoms. Conclusions The use of ILI underestimated the occurrence of RSV-ARTI in community-dwelling older adults up to 9-fold (11% sensitivity). Because worldwide RSV surveillance depends largely on ILI, there is an urgent need for a better approach to measure the occurrence of RSV disease and the impact of future RSV vaccine introduction. Clinical Trials Registration. NCT03621930.

This randomized clinical trial compares the need for re-treatment of respiratory infection following hospitalization for community-acquired pneumonia among children receiving amoxicillin at high doses vs low doses and at 3-days vs 7-days duration. Question For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day noninferior to 70 to 90 mg/kg per day, and is a 3-day course noninferior to 7 days, with regard to the need for antibiotic re-treatment? Findings In this 2 x 2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic re-treatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin. Meaning Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day was noninferior to a dose of 70 to 90 mg/kg per day and 3 days was noninferior to 7 days with regard to the need for later antibiotic re-treatment. Importance The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants Multicenter, randomized, 2 x 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -infinity to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -infinity to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -infinity to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -infinity to 7.4%]; P value for interaction = .73). Conclusions and Relevance Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a randomized, placebo-controlled trial. Patients were prescribed amoxicillin 1 g, three times daily (naEuroS=aEuroS52) or placebo (naEuroS=aEuroS50) for 7 days. Oropharyngeal swabs obtained before, within 48 h post-treatment and at 28-35 days were assessed for proportions of amoxicillin-resistant (ARS; amoxicillin MIC a parts per thousand yen2 mg/L) and -non-susceptible (ANS; MIC a parts per thousand yen0.5 mg/L) streptococci. Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated. ITT and PP analyses were conducted. ARS and ANS proportions increased 11- and 2.5-fold, respectively, within 48 h post-amoxicillin treatment compared with placebo [ARS mean increase (MI) 9.46, 95% CI 5.57-13.35; ANS MI 39.87, 95% CI 30.96-48.78; PaEuroS < aEuroS0.0001 for both]. However, these differences were no longer significant at days 28-35 (ARS MI -3.06, 95% CI -7.34 to 1.21; ANS MI 4.91, 95% CI -4.79 to 14.62; PaEuroS > aEuroS0.1588). ARS/ANS were grouped by pbp mutations. Group 1 strains exhibited significantly lower amoxicillin resistance (mean MIC 2.8 mg/L, 95% CI 2.6-3.1) than group 2 (mean MIC 9.3 mg/L, 95% CI 8.1-10.5; PaEuroS < aEuroS0.0001). Group 2 strains predominated immediately post-treatment (61.07%) and although decreased by days 28-35 (30.71%), proportions remained higher than baseline (18.70%; PaEuroS=aEuroS0.0004). By utilizing oropharyngeal streptococci as model organisms this study provides the first prospective, experimental evidence that resistance selection in patients receiving amoxicillin is modest and short-lived, probably due to 'fitness costs' engendered by high-level resistance-conferring mutations. This evidence further supports European guidelines that recommend amoxicillin when an antibiotic is indicated for community-acquired lower respiratory tract infections.

Background Mixed methods are commonly used in health services research; however, data are not often integrated to explore complementarity of findings. A triangulation protocol is one approach to integrating such data. A retrospective triangulation protocol was carried out on mixed methods data collected as part of a process evaluation of a trial. The multi-country randomised controlled trial found that a web-based training in communication skills (including use of a patient booklet) and the use of a C-reactive protein (CRP) point-of-care test decreased antibiotic prescribing by general practitioners (GPs) for acute cough. The process evaluation investigated GPs’ and patients’ experiences of taking part in the trial. Methods Mixed methods are commonly used in health services research; however, data are not often integrated to explore complementarity of findings. A triangulation protocol is one approach to integrating such data. A retrospective triangulation protocol was carried out on mixed methods data collected as part of a process evaluation of a trial. The multi-country randomised controlled trial found that a web-based training in communication skills (including use of a patient booklet) and the use of a C-reactive protein (CRP) point-of-care test decreased antibiotic prescribing by general practitioners (GPs) for acute cough. The process evaluation investigated GPs’ and patients’ experiences of taking part in the trial. Results Three instances of dissonance occurred in 39 independent findings. GPs and patients reported different views on the use of a CRP test. GPs felt that the test was useful in convincing patients to accept a no-antibiotic decision, but patient data suggested that this was unnecessary if a full explanation was given. Whilst qualitative data indicated all patients were generally satisfied with their consultation, quantitative data indicated highest levels of satisfaction for those receiving a detailed explanation from their GP with a booklet giving advice on self-care. Both qualitative and quantitative data sets indicated higher patient enablement for those in the communication groups who had received a booklet. Conclusions Use of CRP tests does not appear to engage patients or influence illness perceptions and its effect is more centred on changing clinician behaviour. Communication skills and the patient booklet were relevant and useful for all patients and associated with increased patient satisfaction. A triangulation protocol to integrate qualitative and quantitative data can reveal findings that need further interpretation and also highlight areas of dissonance that lead to a deeper insight than separate analyses.

BACKGROUND: Most cases of adult pertussis probably remain undiagnosed. AIM: To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. DESIGN AND SETTING: Prospective observational study between 2007 and 2010 in primary care in 12 European countries. METHOD: Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. RESULTS: Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. CONCLUSION: Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation.