One Dose of Oral Azithromycin Resolves Otitis - Brief Article

0 Comments | Family Practice News, Nov 15, 2000 | by Jennifer M. Wang

It offers compliance advantage over 10-day course of amoxicillin/clavulanate.

NEW ORLEANS -- A single dose of oral azithromycin for acute otitis media is as effective as a 10-day course of amoxicillin/clavulanate, according to the first single-dose oral treatment study for otitis.

"It has the potential for creating a novel treatment alternative for otitis media. The ramifications for compliance are enormous," Dr. Stephen Eppes said in a poster presentation at the annual meeting of the Infectious Diseases Society of America.

The study data are being submitted this fall to the Food and Drug Administration for approval of the new indication, said Dr. Eppes, a pediatric infectious diseases specialist at the Alfred I. duPont Hospital for Children in Wilmington, Del.

In the multicenter, doubleblind, double-placebo trial of 260 children aged 6 months to 12 years, the patients were randomized to receive 30 mg/kg of single dose, oral-suspension azithromycin (Zithromax) plus placebo for 10 days or 45/6.4 mg/kg of amoxicillin/clavulanate (Augmentin) twice daily for 10 days, up to the maximum dosage for 40 kg plus a singledose placebo.

At the "end of treatment" visit between days 12 and 16, 86% of the children receiving azithromycin and 88% of those receiving amoxicillin/ clavulanate were considered treatment successes, defined as the complete resolution of symptoms with or without effusion. At a later visit between days 28 and 32, 75% of children in both groups were considered cured, while six in each group had recurrent disease.

Similar results appeared when the data were broken down by age, Dr. Eppes said in an interview. "The kids under 2 years old were cured at about the same rate as the entire group, even though they tended to be sicker." Children aged 2 and younger achieved resolution rates of 78% with azithromycin and 80% with amoxicillin/clavulanate by days 12-16, and 64% with azithromycin and 57% with amoxicillin/clavulanate by days 28-32.

Overall, 29 (16.8%) children in the azithromycin group reported side effects, compared with 39 (22.5%) children in the amoxicillin/ clavulanate group. Diarrhea and vomiting appeared most often with azithromycin; diarrhea and rash occurred most frequently with amoxicillin/ clavulanate.

The study was limited to children without refractory acute otitis media who had nor previously failed antibiotic therapy. The children were evaluated for clinical response only and were less ill than patients who typically undergo tympanocentesis, said Dr. Stan L. Block, the lead investigator.

He said that shorter follow-up intervals would not have revealed differences in the two therapies. The Centers for Disease Control and Prevention guidelines for treating acute otitis media note that an effective antibiotic should bring about clinical improvement by 3 days of treatment (Pediatr. Infect. Dis. J. 18[1]:1-9, 1999). This happens in 95% of children with nonrefractory acute otitis media regardless of what antibiotics they are put on, said Dr. Block, who practices in Bardstown, Ky.

Double-tap tympanometric, microbiologic studies have shown that more bacteria linger in the body early in treatment with azithromycin than in treatment with amoxicillin/ clavulanate (Pediatr. Infect. Dis. J. 19[2]: 95-104, 2000). But the final clinical result is equal eradication, Dr. Block commented.

Single-dose azithromycin may be a good alternative treatment for the penicillin-allergic child who is difficult to treat, he pointed out. The single-dose administration guarantees patient compliance.

Pfizer, the maker of Zithromax, agreed to sponsor the study when the physicians suggested it based on the favorable pharmacokinetics of azithromycin.

"This is the only drug that makes sense for single-dose treatment" because of its long half-life of about 60 hours, its excellent penetration into tissues, and its high concentration in white blood cells, Dr. Block said.