Topical Antibiotics for Clinical and Microbiologic Cure of Bacterial Conjunctivitis

Sheikh A, Hurwitz B, van Schayck CP, McLean S, Nurmatov U. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev 2012;(9): CD001211.

Study Population: 3,673 patients with bacterial conjunctivitis from 11 trials randomized to topical antibiotics vs. placebo

Time to clinical and microbiologic cure

Adverse outcomes as reported in trials, for example, complications such as bacterial keratitis and orbital cellulitis; adverse reactions to antibiotics were not reported

Acute bacterial conjunctivitis is an infective condition frequently resulting in mucopurulent ocular discharge, bulbar and palpebral injection, and discomfort. It may be difficult to differentiate between viral and bacterial conjunctivitis on clinical grounds, and swabbing eyes for cultures is not considered clinically practical. Therefore, although most cases are self-limited, antibiotics are typically given based on the belief that they decrease time to recovery, reduce sightthreatening complications, and reduce the rate of relapse.

This review, an update of a previous Cochrane review from 2006, included 11 randomized control trials totaling 3,673 patients with bacterial conjunctivitis, whereas the prior review included five randomized control trials and 1,034 patients. The review included trials that made the diagnosis of bacterial conjunctivitis based on either clinical or microbiologic grounds.1 Clinical criteria required varied but generally included ocular discharge and conjunctival injection. Two of the trials required microbiologically proven bacterial conjunctivitis with the remainder making the diagnosis on clinical grounds. The primary outcomes of this review included both clinical and microbiologic cure rates.1 How cure was assessed varied between trials but, in general, it was defined by absence of symptoms or microbiologic eradication.

Data analysis from the trials indicated improved early (2- to 5-day) clinical cure rate of 40% (risk ratio [RR] = 1.36, 95% confidence interval [CI] = 1.15– 1.61) and microbiologic cure (RR = 1.55, 95% CI = 1.37–1.76). At 6 to 10 days (considered the “late” time point) antibiotics continued to show clinical benefit in clinical and microbiologic cure (RR = 1.21, 95% CI = 1.10–1.33; and RR = 1.37, 95% CI = 1.24–1.52 respectively). The absolute risk difference for early and late clinical cure were 11 and 9%, respectively, corresponding to NNTs of 9 and 11.1

Among subjects in the placebo groups, 30% achieved clinical cure by day 5, and 41% of cases had resolved by days 6 to 10. No serious outcomes were reported in either placebo groups or treatment groups.1

Of the 11 included trials, two primary care-based trials were judged by the reviewers to be of high quality, with the remainder graded as being of poor quality. Nine of the 11 studies were judged to have a high risk of bias. Two of the 11 trials were done at primary care sites, and the remainder were performed at specialty care sites, suggesting the possibility of referral bias.1

Interestingly, the natural history of bacterial conjunctivitis could not be inferred from the trials, as some of the trials used placebo eye drops containing an antiseptic that when applied three to four times a day was likely to have some clinical effect. Moreover, all of the included studies utilized different antibiotic regimens, which was a major contributor to the high degree of heterogeneity of the trials. Of note, the majority of the more recent trials utilized fluoroquinolones. Other factors contributing to heterogeneity included patient age, method of diagnosis, and definition of outcome measures. There was no recommendation regarding which antibiotic or duration of treatment was superior. Also of note, only two of the trials required microbiologic evidence to make the diagnosis of bacterial conjunctivitis, while the remainder allowed for bacterial conjunctivitis to be diagnosed clinically. This is a potential limitation of the study as it is possible that other forms of conjunctivitis were being treated.

In this review, 30% of the placebo groups achieved clinical cure by day 5, and 41% had resolved at 6 to 10 days. This suggests that the benefits of antibiotics were reflected in the rate of resolution of conjunctivitis but not in a reduction in complications, since no serious outcomes were reported in treatment or placebo groups.1 Given that complications such as orbital cellulitis are rare, however, a larger trial would be necessary to assess the efficacy of antibiotics in terms of reduction in complications.

In conclusion, despite the limited existing evidence (mostly poor quality with high risk of bias) the demonstration of consistent positive outcomes supports the use of topical antibiotics to treat bacterial conjunctivitis. The risk of adverse events associated with this treatment appear to be minimal. Therefore, we have assigned a color rating of green (benefits > harms) to this treatment.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Topical Antibiotics for Bacterial Conjunctivitis, November 7, 2010

March 29, 2019