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Should We Prescribe Antibiotics for Acute Conjunctivitis? SEAN P. DAVID, M.D., S.M., Brown Medical School, Providence, Rhode Island The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Sean P. David, M.D., S.M., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract. A patient information handout about conjunctivitis, written by the author of this article, is provided on page 1652. Clinical Scenario A 12-year-old girl has a history of two days of red eyes without purulent discharge. On examination, the patient appears nontoxic, is afebrile, has normal visual acuity, and demonstrates moderate bilateral conjunctival and scleral erythema, serous discharge, conjunctival swelling, and a tender preauricular node. Clinical Question Should we prescribe antibiotics for acute conjunctivitis? Evidence-Based Answer This review indicates that even in high-risk patients with bacterial conjunctivitis, there is only a small benefit of treatment with antibiotics. Furthermore, most cases (64 percent) resolve spontaneously, and complications are rare. Therefore, it is reasonable to avoid antibiotic use in a low-risk patient with suspected viral conjunctivitis. Cochrane Abstract Background. There are concerns regarding whether antibiotic therapy confers significant benefit in the treatment of acute bacterial conjunctivitis. Objectives. The aim of this review1 is to assess the benefit and harm of antibiotic therapy in the management of acute bacterial conjunctivitis. Search Strategy. The authors searched the Cochrane Controlled Trials Register, CENTRAL (which contains the Cochrane Eyes and Vision Group specialized register), MEDLINE, EMBASE, and the reference lists of identified trial reports. The authors used the Science Citation Index to look for articles that cited the relevant studies, and they contacted investigators and pharmaceutical companies for information about additional trials. Selection Criteria. The authors included double-blind, randomized, controlled trials in which any form of antibiotic treatment had been compared with placebo in the management of acute bacterial conjunctivitis. This included topical, systemic, and combination (i.e., antibiotics and steroids) antibiotic usage. Data Collection and Analysis. One reviewer extracted data, and the accuracy was checked by a second reviewer. Relative risks were summarized. The authors tested for heterogeneity between studies. Primary Results. This review includes three trials that randomized a total of 527 participants. Another trial, which has been published in abstract form and has yet to be fully reported, currently is awaiting assessment. All of the trials thus far identified appear to have been conducted on a selected specialist-care patient population. The trials were heterogeneous in terms of their inclusion and exclusion criteria, the nature of the intervention, and the outcome measures assessed. Meta-analysis indicates that acute bacterial conjunctivitis frequently is a self-limiting condition, and clinical remission (cure or significant improvement) occurred by days 2 to 5 in 64 percent of patients treated with placebo (99 percent confidence interval [CI], 57 to 71 percent). Treatment with antibiotics was, however, associated with significantly better rates of clinical remission (days 2 to 5, relative risk [RR] 1.31, 99 percent CI, 1.11 to 1.55) with a suggestion that this benefit was maintained for late clinical remission (days 6 to 10, RR 1.27, 99 percent CI, 0.92 to 1.74). Antibiotic treatment was associated with microbiologic remission (pathogen eradication or reduction). No serious outcomes were reported in either the active or placebo arms of these trials, indicating that important sight-threatening complications are an infrequent occurrence. Reviewers' Conclusions. Acute bacterial conjunctivitis frequently is a self-limiting condition, but the use of antibiotics is associated with significantly improved rates of early clinical remission and early and late microbiologic remission. Because trials to date have been conducted in selected specialist-care patient populations, these results might not necessarily be generalizable to a primary care population. A primary carebased trial that is designed to assess the cost-effectiveness of commonly prescribed antibiotics versus placebo in acute bacterial conjunctivitis is warranted. These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in The Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (www.cochrane.org). Cochrane Critique Did the authors address a focused clinical question? Yes. Were the criteria used to select articles for inclusion appropriate? Yes. Is it likely that important relevant articles were missed? No. Was the validity of the individual articles appraised? Yes. Were the assessments of studies reproducible? Yes. Were the results similar from study to study? Yes. Can the results be applied to patient care? Yes. Do the conclusions make clinical and biological sense? Yes. Are the benefits of treatment with antibiotics for acute bacterial conjunctivitis worth the harms and costs? Yes. However, the precision of these results is limited by the grouping of all bacterial causes of conjunctivitis, treatment with three types of antibiotics, and pooling data from one study carried out in a pediatric population,2 one study carried out in an adult population,3 and one study that did not specify the age of the population.4 This systematic review should be applied to primary care settings with caution because most of the patients in the studies were examined in tertiary care settings and might not represent populations presenting in primary care settings. Practice Pointers Conjunctivitis (any inflammatory condition of the membrane that lines the eyelids and covers the exposed surface of the sclera) is the ophthalmologic condition most commonly presenting to primary care physicians, amounting to 1 to 2 percent of ambulatory office visits.5 While the differential diagnosis of conjunctivitis is broad--encompassing infectious and noninfectious etiologies--most cases of conjunctivitis are caused by viruses or bacteria. A risk-stratification strategy that identifies patients with potentially sight-threatening or noninfectious causes of conjunctivitis has been advocated.6 High-risk patients, namely those with hyperacute bacterial conjunctivitis (abrupt onset characterized by copious, yellow-green, purulent discharge that re-accumulates after being wiped away),3 have a sight-threatening condition associated with more virulent pathogens (e.g., Neisseria gonorrhoeae or Neisseria meningitidis) and require prompt ophthalmologic referral.6 These data indicate that five patients with acute bacterial conjunctivitis would need to be treated to result in one patient having an early remission of symptoms. While this might seem like a reasonable trade-off, there is a low risk of complications from untreated bacterial conjunctivitis, and use of antibiotics carries its own risk. Therefore, among low-risk patients with acute bacterial conjunctivitis, a shared decision-making approach seems appropriate. Patients with viral conjunctivitis should be offered supportive care. The author thanks Dr. Kay Dickersin for help in preparing the manuscript. Reading the Numbers It would be ideal to have clinical trials with sufficient sample sizes to detect small but clinically significant benefits of experimental treatments, but this is not always possible. Historically, physicians relied on unstructured reviews of the research literature or on original research reports without access to all available data. As a result, potentially life-saving treatments were sometimes not recognized until investigators collaborated in applying statistical analyses of data (metaanalysis) pooled from several randomized, controlled clinical trials that met strict eligibility criteria, were of high quality, and represented the most complete datasets feasible. For example, between 1959 and 1984, 16 of 20 randomized, controlled trials of intravenous streptokinase (Streptase) in acute myocardial infarction found no significant reduction in mortality, but a meta-analysis of all 20 trials detected a significant reduction in the relative risk of mortality favoring use of streptokinase (odds ratio 0.76, 95 percent CI, 0.66-0.88).7 Using statistical methods described elsewhere, the metaanalyses used by the Cochrane Collaboration and others compare "like with like, avoiding direct comparison of patients in different trials," to maximize the power of several similar studies to detect small but important differences in treatment outcome.8 REFERENCES 1. 1. Sheikh A, Hurwitz B, Cave J. Antibiotics for acute bacterial conjunctivitis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD001211. 2. 2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. Efficacy of topical antibiotic therapy in acute conjunctivitis in children. J Pediatr 1984;104:623-6. 3. 3. Miller IM, Wittreich JM, Cook T, Vogel R. The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The norfloxacinchloramphenicol opthamalic study group. Eye 1992;6(pt 1):111-4. 4. 4. Leibowitz HM. Antibacterial effectiveness of ciprofloxacin 0.3 percent ophthalmic solution in the treatment of bacterial conjunctivitis. Am J Ophthamol 1991;112(suppl 4):29S-33S. 5. 5. Kane KY, Meadows S, Ellis MR, Reust C. When should acute nonvenereal conjunctivitis be treated with topical antibiotics? J Fam Pract 2002;51:312. 6. 6. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998; 57:735-46. 7. 7. Yusuf S, Collins R, Peto R, Furberg C, Stampfer MJ, Goldheber SZ, et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials. Eur Heart J 1985;6:556-85. 8. 8. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985;27:335-71.
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