Azithromycin Beats Tetracycline in Trichiasis Surgery Trial

Laird Harrison

December 15, 2011

December 15, 2011 — Oral azithromycin edged out topical tetracycline in a study on antibiotic therapy after surgery for trichiasis published online December 12 in the Archives of Ophthalmology.

The rate of recurrence of trichiasis was 10% after a single dose of oral azithromycin compared with 13% after topical tetracycline therapy, with the protective effects evident for up to 3 years after surgery, but not significantly different between the 2 drugs (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58 - 1.10) at the 3-year follow-up, reported Fasika Woreta, MD, MPH, from the Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, and colleagues.

Trachoma is the leading infectious cause of blindness, accounting for an estimated 15.5% of blindness worldwide, according to the authors. Years of repeated infection with the Chlamydia trachomatis bacteria lead to chronic follicular conjunctivitis, which may result in scarring of the eyelid and in-turned lashes rubbing against the surface of the eye. This condition is known as trachomatous trichiasis and may result in corneal scarring and eventual blindness.

To determine the effectiveness of the 2 antibiotic regimens, the researchers from Johns Hopkins University and Project ORBIS, Ethiopia, enrolled 1452 patients in the Surgery for Trichiasis, Antibiotics to Prevent Recurrence [STAR] trial. All patients underwent surgery for the syndrome and were randomly assigned to receive either a single 1-g dose of oral azithromycin or 2 doses of topical tetracycline twice a day for 6 weeks.

Researchers reported previously that oral azithromycin reduced the risk of recurrence by 33% compared with topical tetracycline at 1 year.

In the current study, the researchers wanted to find out whether azithromycin maintained its higher effectiveness after 3 years.

Of the patients enrolled in the trial, 484 were assigned to the tetracycline group and 968 to the azithromycin group. The azithromycin group also was originally divided into 2 subgroups. In one of these subgroups, the patients' family was given the azithromycin as well, but after 1 year, no differences between the subgroups emerged, so the results were combined.

Researchers gave either antibiotic to patients who did not have trichiasis 1 year after surgery. A third of the patients originally receiving azithromycin received a course of topical tetracycline, and 17% of those originally assigned to topical tetracycline received oral azithromycin, slightly blurring the 3-year outcome results, the researchers acknowledged.

Compared with the tetracycline group, the original azithromycin group had a 22% lower rate of recurrence of trichiasis 3 years after surgery, but this difference did not reach statistical significance (P = .11 for the cumulative incidence of recurrence of trichiasis by treatment group).

"Trichiasis recurrence rates in the trial remained low for up to 3 years followingsurgery," the authors write. "The protective effect of a single dose of azithromycin was less than at 1 year and, although not statistically significant, was still suggestive up to 3 years following trichiasis surgery."

A multivariate analysis looked at age, sex, severity of entropion, number of eyelashes touching the globe, and which surgeon performed the surgery. After controlling for these variables, azithromycin was protective against trichiasis recurrence compared with topical tetracycline, but the difference was not statistically significant (HR, 0.78; 95% CI, 0.56 - 1.07).

A single dose of azithromycin after surgery is a component of the World Health Organization's strategy for the elimination of trachoma by the year 2020.

In discussing the reasons why azithromycin appeared to work better, the researchers pointed out that the single dose of azithromycin was administered under the observance of healthcare workers, and compliance was 100%.

In the tetracycline group, healthcare workers only observed the first application of ointment, and the researchers did not collect information on compliance for the next 6 weeks, so it is possible that compliance was a factor in the greater success of azithromycin.

The authors also pointed out that azithromycin costs more than tetracycline ($4.60 vs $0.30 per child), but that oral azithromycin "is readily available" in sub-Saharan Africa through donation programs.

The authors have disclosed no relevant financial relationships.

Arch Ophthalmol. Published online December 12, 2011. Full text