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      Delayed antibiotic prescribing strategies for respiratory tract infections in primary care: pragmatic, factorial, randomised controlled trial

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          Abstract

          Objective To estimate the effectiveness of different strategies involving delayed antibiotic prescription for acute respiratory tract infections.

          Design Open, pragmatic, parallel group, factorial, randomised controlled trial.

          Setting Primary care in the United Kingdom.

          Patients 889 patients aged 3 years and over with acute respiratory tract infection, recruited between 3 March 2010 and 28 March 2012 by 53 health professionals in 25 practices.

          Interventions Patients judged not to need immediate antibiotics were randomised to undergo four strategies of delayed prescription: recontact for a prescription, post-dated prescription, collection of the prescription, and be given the prescription (patient led). During the trial, a strategy of no antibiotic prescription was added as another randomised comparison. Analysis was intention to treat.

          Main outcome measures Mean symptom severity (0-6 scale) at days 2-4 (primary outcome), antibiotic use, and patients’ beliefs in the effectiveness of antibiotic use. Secondary analysis included comparison with immediate use of antibiotics.

          Results Mean symptom severity had minimal differences between the strategies involving no prescription and delayed prescription (recontact, post-date, collection, patient led; 1.62, 1.60, 1.82, 1.68, 1.75, respectively; likelihood ratio test χ 2 2.61, P=0.625). Duration of symptoms rated moderately bad or worse also did not differ between no prescription and delayed prescription strategies combined (median 3 days v 4 days; 4.29, P=0.368). There were modest and non-significant differences in patients very satisfied with the consultation between the randomised groups (79%, 74%, 80%, 88%, 89%, respectively; likelihood ratio test χ 2 2.38, P=0.667), belief in antibiotics (71%, 74%, 73%, 72%, 66%; 1.62, P=0.805), or antibiotic use (26%, 37%, 37%, 33%, 39%; 4.96, P=0.292). By contrast, most patients given immediate antibiotics used antibiotics (97%) and strongly believed in them (93%), but with no benefit for symptom severity (score 1.76) or duration (median 4 days).

          Conclusion Strategies of no prescription or delayed antibiotic prescription result in fewer than 40% of patients using antibiotics, and are associated with less strong beliefs in antibiotics, and similar symptomatic outcomes to immediate prescription. If clear advice is given to patients, there is probably little to choose between the different strategies of delayed prescription.

          Trial registration ISRCTN38551726.

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          Most cited references11

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          Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis.

          To systematically review the literature and, where appropriate, meta-analyse studies investigating subsequent antibiotic resistance in individuals prescribed antibiotics in primary care. Systematic review with meta-analysis. Observational and experimental studies identified through Medline, Embase, and Cochrane searches. Review methods Electronic searches using MeSH terms and text words identified 4373 papers. Two independent reviewers assessed quality of eligible studies and extracted data. Meta-analyses were conducted for studies presenting similar outcomes. The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community.
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            Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.

            Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.

              Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions. To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection. A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics). Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics). Symptom duration and severity. A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02). No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.
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                Author and article information

                Contributors
                Role: National Institute for Health Research senior investigator and professor of primary care research
                Role: reader in primary care research
                Role: trial manager
                Role: senior lecturer in primary care research
                Role: reader in health research
                Role: research fellow
                Role: director of the National Institute for Health Research research design service South Central
                Role: research fellow
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2014
                6 March 2014
                : 348
                : g1606
                Affiliations
                [1 ]University of Southampton, Aldermoor Health Centre, Southampton SO16 5ST, UK
                Author notes
                Correspondence to: P Little p.little@ 123456soton.ac.uk
                Article
                litp015183
                10.1136/bmj.g1606
                3944682
                24603565
                b482b1f7-6542-4acc-be10-7245834364e6
                © Little et al 2014

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 5 February 2014
                Categories
                Research

                Medicine
                Medicine

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