The addition of clavulanic acid to amoxicillin does not reduce the risk of pneumonia hospitalization or death compared with amoxicillin alone in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), a study in Respiratory Research suggests.

In this retrospective study, a team of Danish researchers examined clinical outcomes associated with treatment with clavulanic acid plus amoxicillin vs amoxicillin alone in 43,639 patients with AECOPD from the Danish Registry of COPD (DrCOPD). The exposure variable was the first prescription of amoxicillin monotherapy or amoxicillin plus clavulanic acid after inclusion in the DrCOPD.

Using adjusted Cox proportional hazards models, the investigators analyzed the risk of hospitalization or death within a 30-day period. Secondary endpoints included time to all-cause hospitalization or death, time to non-pneumonia hospitalization or death, and time to a new prescription of oral antibiotics for lower respiratory tract infections, pneumonia hospitalization, or death.

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A total of 30,721 patients received amoxicillin with clavulanic acid for the first treatment of AECOPD, while 12,915 patients received amoxicillin alone. The median ages in the amoxicillin/clavulanic acid and amoxicillin monotherapy arms were 70 and 69 years, respectively.

Treatment with amoxicillin alone was associated with a significantly reduced risk of pneumonia hospitalization or death compared with the amoxicillin/clavulanic acid combination treatment (adjusted hazard ratio [aHR], 0.6; 95% CI, 0.5–0.7; P <.0001). Additionally, amoxicillin monotherapy was associated with a significantly greater decreased risk in all-cause hospitalization or death (aHR, 0.8; 95% CI, 0.8–0.9; P <.0001) and non-pneumonia hospitalization or death (aHR, 0.9; 95% CI, 0.9–1.0; P <.0001).

In contrast, treatment with amoxicillin alone was associated with an increased need for additional antibiotics as well as increased risk of pneumonia hospitalization or death (aHR, 1.2; 95% CI, 1.1–1.2; P <.0001). No difference was found between the 2 treatment arms in terms of time to death (aHR, 0.8; 95% CI, 0.6–1.0; P =.0724).

Limitations of this study were the lack of acute physical measures for disease severity as well as the potential residual confounding by indication, as the amoxicillin/clavulanic acid combination regimen was generally administered to patients with more severe AECOPD.

The researchers suggest their study findings are important, given the “need to avoid the use of broad-spectrum antibiotics to reduce the risk of selecting resistant strains and to cause least possible side effects and dysregulation in the patient ́s microbiome.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Bagge K, Sivapalan P, Eklöf J, et al. Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid-data from 43,636 outpatients. Respir Res. 2021;22(1):11. doi:10.1186/s12931-020-01606-7