An antibiotic widely used to treat uncomplicated lower respiratory tract infections had little benefit in a placebo-controlled clinical trial, researchers reported.

Amoxicillin had no effect, compared with placebo, on duration of moderately bad symptoms or average symptom severity, according to Paul Little, MD, of the University of Southampton in Southampton, England, and colleagues.

The drug did prevent new or worsening symptoms, but was also associated with an increased rate of adverse effects, Little and colleagues reported online in The Lancet.

“Patients given amoxicillin don’t recover much quicker or have significantly fewer symptoms,” Little said in a statement. “Using amoxicillin to treat respiratory infections in patients not suspected of having pneumonia is not likely to help and could be harmful.”

Acute but uncomplicated lower respiratory tract infection is very often treated with antibiotics in developed countries, the researchers noted, despite a consensus to restrict their use in such cases.

Part of the reason the practice persists, they added, is the lack of data from placebo-controlled trials that would confirm or deny a benefit.

To help fill the gap, they enrolled 2,061 patients who were treated at primary care practices in 12 European countries for lower respiratory tract infections that had lasted 28 days or less and were not suspected to be pneumonia. Most patients had acute cough with sputum.

Participants were randomly assigned to take amoxicillin (at 1 g three times a day) or an identical-appearing placebo for 7 days.

The primary outcome was duration of symptoms rated “moderately bad” or worse on a 7-point scale, in which 0 was no problem and 6 was “as bad as it could be.” On that scale, 3 was “moderately bad.”

Secondary outcomes were average symptom severity on days 2, 3, and 4 after starting treatment, using the same 7-point scale, as well as new or worsening symptoms, defined as a return to the doctor within 4 weeks of the initial visit with worsening symptoms, new symptoms, new signs, or illness requiring admission to hospital.

The analysis showed no effect on duration of symptoms rated “moderately bad” or worse compared with placebo (hazard ratio 1.06, 95% CI 0.96 to 1.18, P=0.229).

There also was no effect on mean symptom severity. On the 7-point scale, the average symptom severity was 1.69 with placebo and 1.62 with amoxicillin (P=0.074).

However, there was a significant effect on new or worsening symptoms. They were reported by 15.9% of 1,021 amoxicillin patients and 19.3% of 1,006 placebo patients (P=0.043). The number needed to treat to prevent one case was 30.

Finally, there was a significant effect on adverse events. Nausea, rash, or diarrhea were reported by 28.7% of participants in the amoxicillin group and 24% of those in the placebo group (P=0.025). The number needed to harm was 21.

There was one case of anaphylaxis in the amoxicillin group, and one patient who required hospital admission. Two patients in the placebo group needed to be admitted to the hospital. There were no study-related deaths.

A planned subgroup analysis in patients 60 or older mirrored the overall results, Little and colleagues reported.

“Our results show that most people get better on their own,” Little said. “But given that a small number of patients will benefit from antibiotics, the challenge remains to identify these individuals.”

The data are “convincing,” commented Philipp Schuetz, MD, of Kantonsspital Aarau in Aarau, Switzerland.

In an accompanying comment article, Schuetz wrote that the findings “should encourage physicians in primary care to refrain from antibiotic treatment in low-risk patients in whom pneumonia is not suspected.”

“Whether this one size- fits-all approach can be further improved remains to be seen,” he noted, adding “antibiotic treatment might still have a net benefit for selected people,” although any benefit might be outweighed by side effects.

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Primary source: The Lancet
Source reference: Little P, et al “Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial” Lancet 2012; DOI: 10.1016/S1473-3099(12)70300-6.

Additional source: The Lancet
Source reference: Schuetz P “Antibiotics for non-pneumonic respiratory-tract infections” Lancet 2012; DOI: 10.1016/S1473-3099(12)70310-9.