C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Published - Written by Ahmad Zaheen, MD MSc

The 2019 report of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation of chronic obstructive pulmonary disease (COPD) as “an acute worsening of respiratory symptoms that results in additional therapy.” Whether the additional therapy includes antibiotics is largely guided by a 1987 seminal study by Anthonisen and colleagues wherein the cardinal triad of increased dyspnea, sputum volume, and sputum purulence became the standard criteria for considering antibiotics. This study showed that antibiotics were associated with improved symptom resolution in patients with at least two of the three criteria. More than 30 years later, the GOLD report still recommends antibiotics in the presence of the three cardinal symptoms, or two of the three if one is increased sputum purulence.   

COPD exacerbation can certainly be provoked by bacterial infection, but reliably differentiating bacterial infection from viral, environmental, or idiopathic instigators is difficult. Furthermore, some patients experience frequent recurrent exacerbations, and the repeated exposure to broad-spectrum antibiotics increases their risk of opportunistic infection and colonization with drug-resistant organisms, particularly in a population already burdened with bacterial colonization due to structural lung disease. Some restraint in antibiotic prescribing is needed, but a reliable objective measure of bacterial infection in this population is wanting.

In the multicenter, randomized PACE study, Butler and colleagues further the antibiotic debate by showing that C-reactive protein–guided therapy in patients with COPD exacerbations can reduce the rate of antibiotic prescriptions without compromising clinical outcomes. The importance of these findings in the context of antimicrobial stewardship is further discussed in the accompanying editorial.

The following NEJM Journal Watch summary provides more details of the trial and findings.


CRP Testing to Guide Antibiotic Therapy for COPD Exacerbations

Allan S. Brett, MD reviewing Butler CC et al. N Engl J Med 2019 Jul 11 Brett AS and Al-Hasan MN. N Engl J Med 2019 Jul 11

In a randomized trial, point-of-care C-reactive protein measurements lowered antibiotic prescribing without compromising clinical outcomes for patients with chronic obstructive pulmonary disease.

Clinicians often prescribe antibiotics to patients with exacerbations of chronic obstructive pulmonary disease (COPD) — especially those with increased sputum volume and discoloration. However, the evidence supporting antibiotic therapy is mixed. In this U.K. study, researchers sought to determine whether testing for C-reactive protein (CRP) could lower antibiotic prescribing without compromising clinical outcomes. More than 600 patients with COPD exacerbations who presented to primary care practices were randomized to receive point-of-care CRP testing or no CRP testing (i.e., usual care). Based on previously published data, clinicians of patients in the CRP group were urged to prescribe antibiotics when CRP levels were >40 mg/L and not to prescribe antibiotics when levels were <20 mg/L; levels between 20 and 40 mg/L were considered a gray area. Participating practices were supplied with point-of-care CRP testing units, which can generate test results in minutes.

The proportion of patients receiving antibiotics was significantly lower in the CRP group than in the usual-care group (57% vs. 77%). Clinical outcomes such as general health status and eventual need for hospitalization were similar in the two groups.

Comment: This study doesn't tell us whether patients who received antibiotics actually benefited from them, but it does suggest that CRP-guided treatment of outpatients with COPD exacerbations is a safe way to limit antibiotic use; the absolute difference of 20 percentage points means that 1 in 5 patients was spared antibiotic therapy. Clinicians with access to quick-turnaround CRP testing should consider using this strategy.


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 Ahmad is a 2019-2020 editorial fellow at the New England Journal of Medicine. He is from Toronto, Canada where he is completing his training in pulmonary medicine at the University of Toronto.