Amoxicillin Alone Better Than Antibiotic Combo for Treating Exacerbations

In people with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations, the use of amoxicillin alone is associated with better outcomes than treatment with amoxicillin in combination with clavulanic acid, another antibiotic, a Danish study shows.

The study, “Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid—data from 43,636 outpatients,” was published in Respiratory Research.

Acute exacerbations of COPD are events in which a patient’s symptoms get suddenly worse. Since these exacerbations often are associated with bacterial infections, treatment with antibiotics —medications that kill bacteria — is part of the standard of care.

In Denmark, there are two commonly used antibiotic regimens for treating such exacerbations. One is 750 mg of amoxicillin three times daily, while the other is 500 mg of amoxicillin plus 125 mg of clavulanic acid, also thrice daily.

Both amoxicillin and clavulanic acid are beta-lactams, a type of antibiotic that works by interfering with the production of the bacterial cell wall, thereby killing bacteria.

The rationale for combining the two antibiotics is that clavulanic acid is effective against more different types of bacteria. However, treatment with amoxicillin alone means that the single antibiotic can be given at higher doses, which may in the end be more effective at killing bacteria.

Now, a team of researchers in Denmark directly compared the outcomes of COPD exacerbations treated with these two regimens.

Using data from the Danish Registry of COPD, in combination with other national registries, the researchers identified 43,639 patients whose exacerbations had been treated with one of the two regimens under analysis. Specifically, 12,915 were given amoxicillin alone, and 30,721 were given the combination. Notably, none of the analyzed patients were hospitalized due to COPD exacerbations, indicating that the episodes were not severe.

Compared with the amoxicillin-clavulanic acid combination, treatment with amoxicillin alone was associated with a 40% lower risk of pneumonia-related hospitalization or death by all cause after 30 days. Amoxicillin alone also was associated with a 10% lower risk of non-pneumonia hospitalization or death, and a 20% lower risk of all-cause hospitalization or death.

For all of these measures, the difference between the two treatments was statistically significant. Additional statistical analyses generally found consistent results.

“We found a pronounced decreased risk of pneumonia hospitalization or death within 30 days … in AECOPD [acute exacerbation of COPD] outpatients being treated with AMX [amoxicillin alone] compared to AMC [amoxicillin plus clavulanic acid],” the researchers wrote.

The team speculated that one probable reason for this result was the dosing difference between the two antibiotic regimens.

“It would be very unlikely that AMC [the combination] is inferior to AMX [amoxicillin alone] when administered in equal doses,” they wrote.

Overall, the analysis “supports the use of AMX as first choice antibiotic treatment in non-hospitalized patients suffering from AECOPD,” the researchers concluded, as “adding clavulanic acid to amoxicillin is not associated with a better outcome.”

The study’s main limitation, according to the researchers, is the risk of confounding by indication — in other words, it is possible that people who were already in poor condition might have been more likely to be prescribed the combination treatment. While the researchers’ statistical analyses attempted to account for this factor, it remains possible that pre-treatment differences accounted for some of the outcomes.