Topical azithromycin or ofloxacin for endophthalmitis.

The recently published study by Romero-Aroca et al1 raises interesting questions regarding the effect of choice of topical antibiotic (azithromycin versus ofloxacin) on the incidence of endophthalmitis following intravitreal injections. However, important conclusions advanced by the authors deserve further discussion. First, the authors state that use of azithromycin leads to significantly fewer cases of post-injection endophthalmitis than does the use of ofloxacin. Their prospective series shows a lower endophthalmitis rate in eyes treated with azithromycin (two cases in 4045 injections, 0.049%) than in eyes treated with ofloxacin (five cases in 4151 injections, 0.12%). They calculate a relative risk of 2.37, and conclude that this was statistically significant (confidence interval 1.37–3.72; P < 0.001). We believe that this conclusion is wrong because of errors in the statistical computations. When the endophthalmitis incidence rates are compared using both the Chi-square and two-proportion z-tests, the differences between the cohorts are minimal and far from clinically significant (Chi-square 1.211, two-sided z-statistic 1.10; P = 0.27 for both tests). In fact, for these observed rates to yield a significant difference, a trial with 12,000 injections in each group (three times the size reported by the authors) would be necessary. Therefore, with the data presented, it is not possible to detect a meaningful difference in endophthalmitis rates between the two drugs. Contrary to the authors’ assertion, many retrospective and prospective studies have reported the incidence of endophthalmitis after injections. In the largest prospective age-related macular degeneration trials to date (VIEW 1 and 2),2 six cases of endophthalmitis occurred after 27,112 (0.022% or one in 4519) injections in 2457 patients. This endophthalmitis rate is similar to the rates reported in the two largest published series of injections (one in 4059 patients and the other in 8617 patients).3,4 This leads to the second important point, ie, the authors performed their study under the assumption that prophylactic topical antibiotics lower the incidence of post-injection endophthalmitis. However, to date, no studies have shown that use of prophylactic antibiotics lowers the rate of post-injection endophthalmitis. No differences in antibiotic-related endophthalmitis rates were identified in the largest retrospective series, and as a result, many surgeons have abandoned such use of antibiotics. The conclusions advanced by Romero-Aroca et al also have significant financial implications. Recent data show that more than 220,000 patients (2008 Medicare data) in the US receive intravitreal injections each year.5 Single bottles of azithromycin and ofloxacin cost $108 and $18, respectively, and if these were prescribed once yearly for each patient receiving injections, the total cost would range from $3.96 million to $23.76 million. Given that neither drug has been shown to lower the rate of endophthalmitis, this probably represents a significant waste of money. We applaud the interest of Romero-Aroca et al in endophthalmitis, but we must challenge both the conclusions of their paper and the overall effectiveness of post-injection antibiotics.