Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid\u2014data from 43,636 outpatients

Christian Østergaard Andersen,Josefin Eklöf,Jens-Ulrik Stæhr Jensen,Ejvind Frausing Hansen,Frederik Böetius Hertz,Pradeesh Sivapalan,Kristian Bagge,Jens Otto Jarløv

doi:10.1186/s12931-020-01606-7

Abstract

BackgroundFor antibiotic treatment of Acute exacerbations of COPD (AECOPD) the National guidelines in Denmark recommend either first choice amoxicillin 750 mg TID (AMX) or amoxicillin with clavulanic acid 500 mg/125 mg TID (AMC). Addition of clavulanic acid offers a broader spectrum; opposite, AMX alone in a higher dose may offer more time above MIC. The aim of this study was to determine which of these regimens is associated with better outcome.MethodsThe Danish Registry of COPD (DrCOPD), a nationwide outpatient COPD registry, was crosslinked with medication data and hospital contacts. The first prescription of AMX or AMC after inclusion in DrCOPD was used as exposure variable. Adjusted Cox proportional hazards models were used to analyze the risk of hospitalization or death (combined) within 30 days and other endpoints.ResultsFor the first treatment of AECOPD 12,915 received AMX, and 30,721 patients received AMC. AMX was associated with a decreased risk of pneumonia hospitalization or death (aHR 0.6, 95% CI 0.5–0.7; p < 0.0001) compared to AMC.ConclusionIn AECOPD, empirically adding clavulanic acid to amoxicillin is not associated with a better outcome; it seems safe for these patients to be treated with amoxicillin alone.

Highlights

Acute exacerbations (AECOPD) of chronic obstructive pulmonary disease (COPD) contribute to high morbidity and mortality [1,2,3]
Today amoxicillin (AMX) 750 mg three times daily (TID) is recommended as first choice empirical treatment of Acute exacerbations of COPD (AECOPD) in Denmark in mild to moderate cases, many clinicians prefer amoxicillin with clavulanic acid (AMC) 500/125 mg TID, as recommended in the previous guideline, referring to the fact that AMC is effective against Moraxella catarrhalis [10,11,12]
AMC has a broader spectrum of activity, and on the other hand, amoxicillin mg TID (AMX) is most often administered at a higher dose of amoxicillin (750 mg vs. 500 mg), which may increase the time above the minimal inhibitory concentration (MIC) for many pathogenic bacteria

Summary

Introduction

Acute exacerbations (AECOPD) of chronic obstructive pulmonary disease (COPD) contribute to high morbidity and mortality [1,2,3]. Today amoxicillin (AMX) 750 mg three times daily (TID) is recommended as first choice empirical treatment of AECOPD in Denmark in mild to moderate cases, many clinicians prefer amoxicillin with clavulanic acid (AMC) 500/125 mg TID, as recommended in the previous guideline, referring to the fact that AMC is effective against Moraxella catarrhalis [10,11,12]. AMC has a broader spectrum of activity, and on the other hand, AMX is most often administered at a higher dose of amoxicillin (750 mg vs 500 mg), which may increase the time above the minimal inhibitory concentration (MIC) for many pathogenic bacteria. For antibiotic treatment of Acute exacerbations of COPD (AECOPD) the National guidelines in Denmark recommend either first choice amoxicillin 750 mg TID (AMX) or amoxicillin with clavulanic acid 500 mg/125 mg TID (AMC). The aim of this study was to determine which of these regimens is associated with better outcome

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Conclusion