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SOUTHAMPTON, England, Dec. 4 -- Amoxicillin and nasal budesonide were no more effective than placebo in treating acute sinus infections in a randomized trial, researchers here found.

Median total symptom severity (TSS) scores for the two drugs together, each drug alone, and placebo were similar on every day of the study and reached zero on the ninth day for every treatment, reported Ian G. Williamson, M.D., of the University of Southampton, and colleagues, in the Dec. 5 issue of the Journal of the American Medical Association.

"Neither an antibiotic nor a topical steroid alone or in combination are effective in altering the symptom severity, the duration, or the natural history of the condition," the researchers said.

However, a subgroup analysis indicated that budesonide had a significant benefit on certain symptoms when they were initially mild.

Up to 92% of patients with acute sinusitis in Britain and 85% to 98% of such patients in the U.S. receive antibiotics, even though doctors rarely confirm a bacterial infection, the group said.

In an accompanying editorial, Morten Lindbaek, M.D., of the University of Oslo, said that, based on the results of this study, "cautious use of antibiotics in the general practice setting for patients with sinusitis is warranted."

Dr. Williamson and his colleagues said theirs was the largest randomized, placebo-controlled study of amoxicillin in acute sinus infection ever conducted without pharmaceutical company funding, and the only "adequately powered" study of budesonide in these patients.

The double-blind study involved 240 patients seen in family practice clinics over a four-year period for uncomplicated acute sinusitis. They were assigned to four treatment groups: 500 mg of oral amoxicillin three times a day for seven days plus a nasal placebo; 200 micrograms of budesonide nasal spray once daily for 10 days plus an oral placebo; both active drugs; and both placebos.

Patients assessed their own symptoms on a seven-point severity scale, in categories including blockage and discharge for each nostril, four types of pain, unpleasant taste or smell, feelings of illness, and activity restriction. Patients tracked symptoms in a diary, which was to be turned in after two weeks or when they scored all symptoms as zero.

Diaries were not collected from 31 patients and two patients dropped out of the study because of ongoing symptoms, leaving 207 patients in the primary analysis.

Amoxicillin, either by itself or combined with budesonide, showed no significant effects on severity or duration of symptoms relative to placebo.

Symptoms lasted 10 or more days for 29% of patients on amoxicillin compared with 33.6% for those not taking amoxicillin (adjusted odds ratio: 0.99, 95% CI: 0.57 to 1.73) and for 31.4% of patients on topical budesonide compared with an equal percentage among those not taking budesonide (adjusted odds ratio: 0.93, 95% CI: 0.54 to 1.62).

Anticipating criticism that the study involved a single antibiotic, Dr. Williamson's group cited studies showing similar effects in sinusitis for multiple antibiotic classes. "It is unlikely that a different antibiotic would have produced different results," they said.

Budesonide did have a detectable benefit in two symptom categories, "unwell" feelings and activity restriction, in patients who graded these symptoms as mild at presentation. The amount of improvement declined with increasing initial symptom severity, and the drug was a clear detriment to patients with more severe initial symptoms.

Dr. Williamson and his group calculated that budesonide's benefit relative to placebo at day 10 decreased by 0.28 points (P=0.003, 95% CI: 0.10 to 0.45) for each 1-point increase in initial severity of the unwellness and activity symptoms.

Under this linear model, patients with initial scores of 1 for these symptoms had a benefit of 0.47 points at day 10 with budesonide. Those with baseline scores of 5 on these symptoms worsened by 0.65 points with budesonide.

Commenting on the clinical implications of their study, the researchers said that "topical steroids (because of their local method of delivery to the mucosa) are more likely to be of benefit at an early stage" of sinusitis.

Budesonide showed no effects on other symptoms in any patient subgroup.

Dr. Lindbaek said the results were largely in line with previous research.

"This study reinforces the lack of benefit from antibiotics shown in a number of other studies that recruited patients based on clinical symptoms and findings," he said. "Most patients with acute purulent sinusitis recover without antibiotic treatment, as was also observed in a study that used sinus computed tomography scans as the diagnostic standard."

However, he said, the small minority of sinusitis patients who have fever, malaise, and poor overall condition "still are in need of antibiotics."

He said the evidence was equivocal for the use of nasal steroids in acute sinusitis. One large study found a statistically significant benefit, he said, but the clinical difference from placebo "was modest at best."

Dr. Lindbaek said there may be patient subgroups, like the one identified in the Southampton study, that would show more benefit from either antibiotics or nasal steroids. These might be identifiable in a large meta-analysis of individual patient data from multiple trials, he said.

The study was funded by the U.K. Department of Health. One co-author reported a financial relationship with Abbott Pharmaceuticals.

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