17 October 2011
An individual patient data meta-analysis1 of three randomised controlled trials (RCTs) found that overall there was a small significant benefit of topical antibiotics in acute infective conjunctivitis, compared with control (number needed to treat [NNT] 13 for cure at day 7). However, when only the two RCTs that used a placebo control (rather than no treatment) were analysed, there was no significant difference. Most people recovered by day 7 regardless of whether an antibiotic was used, even when the cause was bacterial.
Level of evidence:
Level 2 (limited quality patient-oriented evidence) according to the SORT criteria.
As most people with acute infective conjunctivitis will get better without the need for topical antibiotics, health professionals should follow guidance from the Health Protection Agency (HPA). This states that conjunctivitis should be treated only if symptoms are severe. However, a shared decision-making approach will be needed to determine the best strategy for an individual patient — i.e. antibiotics, delayed antibiotic prescription, or no treatment. Prescribers and community pharmacists should weigh these new data in discussions with patients about the pros and cons of treatment, consider their expectations of antibiotic use, and provide reassurance about the self-limiting nature of the condition.
What is the background to this?
Acute infective conjunctivitis is commonly seen in primary care. HPA guidance on the management of infection in primary care recommends that conjunctivitis should be treated only if severe, as most infections are viral or self-limiting. It also advises that bacterial conjunctivitis is usually unilateral and is characterised by red eye with mucopurulent (not watery), discharge. Bacterial and viral conjunctivitis may be difficult to differentiate on clinical grounds, and many presumed cases of infective conjunctivitis are treated with topical antibiotics. Chloramphenicol eye drops are also available over-the-counter (OTC) for supply by community pharmacists.
This meta-analysis of individual patient data aimed to determine the benefit of antibiotics for the treatment of acute infective conjunctivitis in primary care, and which subgroups of patients may benefit most.
What does this study claim?
This study1 (n=622) claims that topical antibiotics are of limited benefit in acute infective conjunctivitis. Overall, significantly more patients (80%) who received antibiotics were cured at day 7, compared with 71%* of patients who received controls (placebo or no treatment) — relative risk (RR) 1.11 95% confidence interval (CI) 1.02 to 1.21, absolute risk reduction (ARR) 0.08, 95% CI 0.01 to 0.14, NNT 13. When 2 RCTs (n=480) that used a placebo control (rather than no treatment) were analysed, there was no significant benefit — RR 1.05, 95% CI 0.95 to 1.15. Subgroup analyses suggested that patients with purulent discharge and mild severity of red eye may gain benefit from an antibiotic, and purulent discharge and age less than five years were found to be predictors of a positive culture. However, bacterial culture positivity was not an indicator of benefit from antibiotics — RR for cure by day 7 in those with a positive culture (n=292) 1.11, 95% CI 0.99 to 1.24.
*This figure was incorrectly stated as 74% in the paper.
How does this relate to other studies?
A Cochrane review (5 RCTs, n=1034) of antibiotics versus placebo for acute bacterial conjunctivitis found that the use of antibiotics is associated with significantly improved rates of clinical and microbiological remission. However, they concluded that the condition is frequently self-limiting and most cases resolve spontaneously, with clinical remission being achieved in 65% (95% CI 59 to 70) by days 2 to 5 in those receiving placebo. This review included three studies conducted in secondary care, which were also considered to be of lower methodological quality.
This meta-analysis1 suggests most people with acute infective conjunctivitis will get better without antibiotics, even when there is a bacterial cause. A limited group of patients may obtain a small benefit from topical antibiotics — i.e. patients with purulent discharge and patients with mild severity of red eye. The authors hypothesise that this could be because viral and allergic causes of conjunctivitis, as well as alternative diagnoses such as episcleritis, may give a more dramatically red eye. It may also be that in patients with only mild red eye, the diagnosis of acute infective conjunctivitis hinges more on the presence of more specific signs and symptoms, such as purulent discharge. However, the study authors suggest that even in these subgroups the benefit of antibiotics is limited.Study details
When placebo drops were used as the comparator, there was no significant difference between the antibiotic and placebo groups. This may suggest that the irrigation effect of placebo drops is helpful, without the need for antibiotic treatment. This study also found that even in patients with a positive bacterial culture, antibiotics were not significantly better than control. Obtaining eye swabs for microbiological culture has previously been shown not to improve outcomes and to increase patient concerns. This study seems to support the view that they should not be used.
Prescribing rates of topical antibiotics have been falling, but there were still more than 2.5 million items of chloramphenicol and fusidic acid prescribed in general practice in England from April 2010 to March 2011. Since 2005, OTC availability of topical chloramphenicol in the UK has resulted in a 48% increase in its use.2 The authors suggest that prescribing practices and OTC policies (Royal Pharmaceutical Society practice guidance) need to be updated to reflect these findings.
In clinical practice, it is likely that shared decision-making will be important to determine the best strategy for an individual patient. Clinicians (both prescribers and community pharmacists) will need to weigh these new data in discussions about the pros and cons of treatment, consider patient expectations of antibiotic use, and provide reassurance about the self-limiting nature of the condition. Patient information leaflets and/or a delayed prescription strategy may also be useful. This meta-analysis only compared antibiotics with placebo or no treatment, and excluded a study arm of one RCT which also compared antibiotics with a delayed prescription strategy. This study found that delayed prescribing reduced antibiotic use, provided similar duration and severity of symptoms to immediate prescribing, and reduced reattendance for eye infections.
- Jefferis J, et al. Acute infective conjunctivitis in primary care: who needs antibiotics? Br J Gen Pract 2011;61:e542–8 (subscription required to access paper)
- Davis H, et al. Topical antibiotic use for acute infective conjunctivitis: relative impact of clinical evidence and over the counter prescribing. Br J Gen Pract 2009;59:897–900 (subscription required to access paper)
Individual patient data meta-analysis of 3 RCTs.
622 patients with acute infective conjunctivitis treated in primary care.
Intervention and comparison
Topical antibiotic versus placebo or no treatment.
Outcomes and results
The main outcome measure was cure at day 7. See Table 1 below for results.
Table 1. Subgroup analysis for the outcome cured at day 7
No. of patients
Antibiotic vs. Control
NNT for cure at day 7
|All cases||622||1.11 (1.02 to 1.21)||0.08 (0.01 to 0.14)||13|
|Type of control|
|Placebo||480||1.05 (0.95 to 1.15)||0.03 (–0.04 to 0.11)|
|Non placebo||142||1.40 (1.13 to 1.73)||0.23 (0.08 to 0.37)||5|
|Negative||255||1.02 (0.88 to 1.19)||0.02 (–0.09 to 0.12)|
|Positive||292||1.11 (0.99 to 1.24)||0.08 (–0.01 to 0.17)|
|Non-purulent||266||1.12 (0.96 to 1.31)||0.08 (–0.03 to 0.19)|
|Purulent||353||1.12 (1.00 to 1.25)||0.09 (0.01 to 0.17)||12|
|Mild||365||1.13 (1.02 to 1.25)||0.10 (0.02 to 0.18)||10|
|Moderate/severe||234||1.10 (0.91 to 1.33)||0.06 (–0.06 to 0.18)|
|<5||287||1.09 (0.98 to 1.22)||0.07 (–0.01 to 0.16)|
|5–18||97||1.05 (0.88 to 1.24)||0.04 –0.10 to 0.18)|
Sponsorship No funding received.
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