[e-drug] Delay antibiotics for upper respiratory tract infections and conjunctivitis

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E-DRUG: Delay antibiotics for upper respiratory tract infections and conjunctivitis
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[The BMJ editorial below outlines the growing evidence of the usefulness of delayed prescribing as a means of limiting antibiotic use in the community, focusing on uncomplicated upper respiratory tract infections and conjunctivitis. The new evidence - on delayed prescribing in conjunctivitis - appears in this week's BMJ (abstract below). Thanks to Andy for spotting this; copied as fair use. WB]

http://bmj.bmjjournals.com/cgi/content/full/333/7563/311
BMJ  2006;333:311-312 (12 August), doi:10.1136/bmj.333.7563.311 
Editorial
Antibiotics for upper respiratory tract infections and conjunctivitis in primary care - Reconsideration of prescription policy is needed 

Although upper respiratory tract infections and acute infective conjunctivitis are minor illnesses that are usually self limiting, the use of antibiotics in these disorders is high.1-4 Two papers in the BMJ by Arroll and Kenealy and Everitt and colleagues help clarify the role of antibiotics in the treatment of uncomplicated upper respiratory tract infections and acute infective conjunctivitis in primary care.5 6 

Randomised controlled trials and meta-analyses of such trials have shown that antibiotics provided mainly short term benefit and the reduction in symptoms was too limited to justify the use of antibiotics for these minor disorders.1-4 The number needed to treat to reduce pain at two to seven days in children with acute otitis media is 15 (95% confidence interval 11 to 24) and the number needed to treat to cure one patient with a sore throat at one week is 14 (12 to 21).1 2 This is also true for the common cold and acute infectious conjunctivitis.3 4 

The systematic review by Arroll and Kenealy found only a clinically marginal benefit of antibiotic treatment for acute (duration less than 10 days) purulent rhinitis in patients in primary care. The number needed to treat at five to eight days ranged from seven (4 to 24) to 15 (8 to 53), depending on whether the patient's background probability of cure was 85% or 38%.5 The benefit of antibiotics for acute purulent rhinitis may even be overestimated as a funnel plot showed only a few small studies with small or no effect. 

In Western countries, withholding antibiotics for these minor complaints can be considered harmless. Although antibiotics reduce the incidence of suppurative (for example, peritonsillar abscess) and non-suppurative (for example, rheumatic fever) complications in patients with a sore throat,2 the incidence of such complications has declined sharply in Western countries in the past decades. None of the 5856 patients taking placebo in trials undertaken since 1975 developed rheumatic fever. The same trend was found for the incidence of peritonsillar abscess in patients with sore throat. In a meta-analysis on acute otitis media in young children only one serious complication (mastoiditis) occurred in the antibiotic treated group and none in the controls.1 Meta-analyses of infective conjunctivitis, the common cold, and chronic purulent rhinitis also found no complications in the placebo groups.3 4 

Antibiotics can have negative effects such as increased antibiotic resistance and adverse side effects. In minor self limiting illnesses the harmful effects of antibiotics (nausea, vomiting, diarrhoea, and rash) may outweigh the benefits. The meta-analysis by Arroll and Kenealy showed this clearly, as the number needed to harm for acute purulent rhinitis overlapped with the number needed to treat: the number needed to harm ranged from 12 (6 to 53) to 78 (38 to 357).5 A similar effect was seen in acute otitis media; the number needed to harm ranged from 6.5 (3.9 to 18.1) to 170 (83 to 571).1 Prescribing antibiotics for upper respiratory tract infections can strengthen patients' belief in antibiotics (perhaps inappropriately) and could be viewed as excessive interference by the medical profession. The randomised trial by Everitt and colleagues found that this is also true for acute infective conjunctivitis.6 Patients with conjunctivitis who received antibiotics immediately were more likely to say they would re-attend with subsequent eye infections than those who were not prescribed antibiotics or received them at a later date. 

In major illness the risk to benefit ratio may not have an important role in the decision about treatment with antibiotics-usually there is no choice. Antibiotic treatment is more effective in certain subgroups of patients (such as those with confirmed bacterial infection), and in others treatment might be necessary to prevent a severe course of disease. A meta-analysis of patients with a sore throat found that on day 3 antibiotics reduced symptoms in patients with a culture positive infection with Streptococcus species compared with those with a negative culture; the number needed to treat ranged from 6.5 (6.1 to 7.3) to 10.2 (8.0 to 13.3).2 

To help doctors identify these subgroups, diagnostic or prognostic indices are needed that can identify a bacterial cause of disease at an early stage. Such a diagnostic index for people with acute infective conjunctivitis was published in the BMJ in 2004.7 However, further research is warranted, including meta-analyses of data on individual patients from the original trials on upper respiratory tract infections and acute infective conjunctivitis, which may show who would benefit most from antibiotic treatment.8 9 

What does all this imply for daily practice? Although antibiotics shorten the duration of symptoms and protect against complications, the benefit is small and often absent. Patients can be protected from complications only by treating many who will not benefit and may actually be harmed by the treatment. The evidence indicates that reserved prescribing of antibiotics for upper respiratory tract infections and acute infective conjunctivitis is justified. 

Delayed prescription of antibiotics is a good alternative for patients with a progressive course of disease or for those patients with a strong preference for antibiotics; it is a safe strategy to reduce the number of prescriptions in patients with upper respiratory tract infections and acute infective conjunctivitis.6 10 

Remco P Rietveld, general practitioner 
Division of Clinical Methods and Public Health, Department of General Practice, Academic Medical Centre, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands 
(r.p.rietveld@amc.uva.nl) 

Patrick J E Bindels, professor of general practice 
Division of Clinical Methods and Public Health, Department of General Practice, Academic Medical Centre, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands 

Gerben ter Riet, epidemiologist 
Horten Centre, University of Zurich, Switzerland 

References
1. Glasziou PP, Del Mar CB, Sanders SL, Hayem M. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2004;1:CD000219. 
2. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2004;2:CD000023. 
3. Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database of Systematic Reviews 2005;3:CD000247. 
4. Sheikh A, Hurwitz B. Topical antibiotics for acute bacterial conjunctivitis: Cochrane systematic review and meta-analysis update. Br J Gen Pract 2005;55: 962-4.
5. Arroll B, Kenealy T. Are antibiotics effective for acute purulent rhinitis? Systematic review and meta-analysis of placebo controlled randomised trials. BMJ 2006;333: 279-81.
6. Everitt HA, Little PS, Smith PWF. A randomised controlled trial of management strategies for acute infective conjunctivitis in general practice. BMJ 2006;333: 321-4. 
7. Rietveld RP, Riet ter G, Bindels PJE, Sloos JH, Weert van HCPM. Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms. BMJ 2004;329: 206-8.
8. Stewart LA, Parmar MK. Meta-analysis of the literature or of individual patient data: is there a difference? Lancet 1993;341: 418-22.
9. Stewart LA, Tierney JF. To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof 2002;25: 76-97.
10. Spurling GKP, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for symptoms and complications of respiratory infections. Cochrane Database of Systematic Reviews 2004;4:CD004417. 

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http://bmj.bmjjournals.com/cgi/content/abstract/333/7563/321
BMJ  2006;333:321 (12 August), doi:10.1136/bmj.38891.551088.7C (published 17 July 2006) 
A randomised controlled trial of management strategies for acute infective conjunctivitis in general practice 

Hazel A Everitt, MRC research training fellow1, Paul S Little, professor of primary care research1, Peter W F Smith, professor of social statistics2 

1 Primary Medical Care, University of Southampton, Aldermoor Health Centre, Southampton SO16 5ST, 2 Southampton Statistical Sciences Research Institute, University of Southampton 

Correspondence to: H A Everitt hae1@soton.ac.uk 

Abstract

Objective To assess different management strategies for acute infective conjunctivitis. 

Design Open, factorial, randomised controlled trial. 

Setting 30 general practices in southern England. 

Participants 307 adults and children with acute infective conjunctivitis. 

Intervention One of three antibiotic prescribing strategies-immediate antibiotics (chloramphenicol eye drops; n = 104), no antibiotics (controls; n = 94), or delayed antibiotics (n = 109); a patient information leaflet or not; and an eye swab or not. 

Main outcome measures Severity of symptoms on days 1-3 after consultation, duration of symptoms, and belief in the effectiveness of antibiotics for eye infections. 

Results Prescribing strategies did not affect the severity of symptoms but duration of moderate symptoms was less with antibiotics: no antibiotics (controls) 4.8 days, immediate antibiotics 3.3 days (risk ratio 0.7, 95% confidence interval 0.6 to 0.8), delayed antibiotics 3.9 days (0.8, 0.7 to 0.9). Compared with no initial offer of antibiotics, antibiotic use was higher in the immediate antibiotic group: controls 30%, immediate antibiotics 99% (odds ratio 185.4, 23.9 to 1439.2), delayed antibiotics 53% (2.9, 1.4 to 5.7), as was belief in the effectiveness of antibiotics: controls 47%, immediate antibiotics 67% (odds ratio 2.4, 1.1 to 5.0), delayed antibiotics 55% (1.4, 0.7 to 3.0), and intention to reattend for eye infections: controls 40%, immediate antibiotics 68% (3.2, 1.6 to 6.4), delayed antibiotics 41% (1.0, 0.5 to 2.0). A patient information leaflet or eye swab had no effect on the main outcomes. Reattendance within two weeks was less in the delayed compared with immediate antibiotic group: 0.3 (0.1 to 1.0) v 0.7 (0.3 to 1.6). 

Conclusions Delayed prescribing of antibiotics is probably the most appropriate strategy for managing acute conjunctivitis in primary care. It reduces antibiotic use, shows no evidence of medicalisation, provides similar duration and severity of symptoms to immediate prescribing, and reduces reattendance for eye infections. 

Trial registration Current Controlled Trials ISRCTN32956955 [controlled-trials.com]