Objective To assess the overall effect of delayed antibiotic prescribing on average symptom severity for patients with respiratory tract infections in the community, and to identify any factors modifying this effect. Design Systematic review and individual patient data meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO CINAHL Plus, and Web of Science. Eligibility criteria for study selection Randomised controlled trials and observational cohort studies in a community setting that allowed comparison between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing. Main outcome measures The primary outcome was the average symptom severity two to four days after the initial consultation measured on a seven item scale (ranging from normal to as bad as could be). Secondary outcomes were duration of illness after the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale. Results Data were obtained from nine randomised controlled trials and four observational studies, totalling 55 682 patients. No difference was found in follow-up symptom severity (seven point scale) for delayed versus immediate antibiotics (adjusted mean difference −0.003, 95% confidence interval −0.12 to 0.11) or delayed versus no antibiotics (0.02, −0.11 to 0.15). Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics. Complications resulting in hospital admission or death were lower with delayed versus no antibiotics (odds ratio 0.62, 95% confidence interval 0.30 to 1.27) and delayed versus immediate antibiotics (0.78, 0.53 to 1.13). A significant reduction in reconsultation rates (odds ratio 0.72, 95% confidence interval 0.60 to 0.87) and an increase in patient satisfaction (adjusted mean difference 0.09, 0.06 to 0.11) were observed in delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. Children younger than 5 years had a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics (adjusted mean difference 0.10, 95% confidence interval 0.03 to 0.18), but no increased severity was found in the older age group. Conclusions Delayed antibiotic prescribing is a safe and effective strategy for most patients, including those in higher risk subgroups. Delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing. Delayed prescribing could reduce reconsultation rates and is unlikely to be associated with an increase in symptoms or illness duration, except in young children. Study registration PROSPERO CRD42018079400.

OBJECTIVES: To assess the effectiveness and safety of delayed antibiotic prescription (DAP) compared to immediate antibiotic prescription (IAP) and no antibiotic prescription (NAP) in children with uncomplicated respiratory infections. METHODS: Randomized clinical trial comparing 3 antibiotic prescription strategies. The participants were children with acute uncomplicated respiratory infections attended to in 39 primary care centers. Children were randomly assigned into prescription arms as follows: (1) DAP, (2) IAP, or (3) NAP. Primary outcomes were symptom duration and severity. Secondary outcomes were antibiotic use, parental satisfaction, parental beliefs, additional primary care visits, and complications at 30 days. RESULTS: In total, 436 children were included in the analysis. The mean (SD) duration of severe symptoms was 10.1 (6.3) for IAP, 10.9 (8.5) for NAP, and 12.4 (8.4) for DAP (P = .539), although the differences were not statistically significant. The median (interquartile range) of the greatest severity for any symptom was similar for the 3 arms (median [interquartile range] score of 3 [2–4]; P = .619). Antibiotic use was significantly higher for IAP (n = 142 [96%]) compared to DAP (n = 37 [25.3%]) and NAP (n = 17 [12.0%]) (P < .001). Complications, additional visits to primary care, and satisfaction were similar for all strategies. Gastrointestinal adverse effects were higher for IAP. CONCLUSIONS: There was no statistically significant difference in symptom duration or severity in children with uncomplicated respiratory infections who received DAP compared to NAP or IAP strategies; however, DAP reduced antibiotic use and gastrointestinal adverse effects.

IntroductionDelayed prescribing can be a useful strategy to reduce antibiotic prescribing, but it is not clear for whom delayed prescribing might be effective. This protocol outlines an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) and observational cohort studies to explore the overall effect of delayed prescribing and identify key patient characteristics that are associated with efficacy of delayed prescribing.Methods and analysisA systematic search of the databases Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus and Web of Science was conducted to identify relevant studies from inception to October 2017. Outcomes of interest include duration of illness, severity of illness, complication, reconsultation and patient satisfaction. Study authors of eligible papers will be contacted and invited to contribute raw IPD data. IPD data will be checked against published data, harmonised and aggregated to create one large IPD database. Multilevel regression will be performed to explore interaction effects between treatment allocation and patient characteristics. The economic evaluation will be conducted based on IPD from the combined trial and observational studies to estimate the differences in costs and effectiveness for delayed prescribing compared with normal practice. A decision model will be developed to assess potential savings and cost-effectiveness in terms of reduced antibiotic usage of delayed prescribing and quality-adjusted life years.Ethics and disseminationEthical approval was obtained from the University of Southampton Faculty of Medicine Research Ethics Committee (Reference number: 30068). Findings of this study will be published in peer-reviewed academic journals as well as General Practice trade journals and will be presented at national and international conferences. The results will have important public health implications, shaping the way in which antibiotics are prescribed in the future and to whom delayed prescriptions are issued.PROSPERO registration numberCRD42018079400.