Can CRP testing guide antibiotic prescription for COPD exacerbations?

COPD Exacerbations — A Target for Antibiotic Stewardship

Patients with acute exacerbations of COPD in whom outpatient treatment fails are at risk for serious decompensation and hospitalization. Thus, when outpatients with COPD present with acutely worsening symptoms, clinicians are tempted to err on the side of doing more, which usually entails prescribing both oral glucocorticoids and antibiotics. However, not all acute exacerbations are provoked by respiratory tract infection, and of those that are, it is difficult to distinguish whether viruses or bacteria are responsible. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use.

Antibiotic therapy for outpatients with COPD exacerbations has traditionally been guided by the criteria outlined by Anthonisen and colleagues1 in 1987 — increased dyspnea, increased sputum volume, and increased sputum purulence. However, these recommendations are not based on robust evidence. The Anthonisen criteria were defined in a randomized trial conducted more than 30 years ago, in which patients with COPD exacerbations received antibiotic therapy or placebo. However, in a more recent randomized trial, only patients with increased sputum purulence benefited from antibiotic thera- py with amoxicillin–clavulanate, regardless of the presence or absence of the other two criteria.

This multisite, randomized trial enrolled 653 patients with known COPD who presented to primary care practices in the United Kingdom with at least one of the Anthonisen criteria for acute exacerbation. One group under- went point-of-care measurement of the C-reactive protein (CRP) level, an acute-phase biomarker that was found to predict response to antibiotics in a previous trial.4,5 For the patients in this group, clinicians were advised that antibiotics are un- likely to be beneficial when the CRP level is lower than 20 mg per liter, likely to be beneficial when the CRP level is higher than 40 mg per liter, and possibly beneficial when the CRP level falls between these extremes and purulent sputum is present. Clinicians were asked to base prescribing decisions on “a comprehensive assessment of likely risks and benefits” and not solely on the CRP level. Decision making for patients in the control group did not involve CRP testing.

The trial achieved its objective, which was to show that CRP testing safely reduces antibiotic use. The percentage of patients who reported using antibiotics within 4 weeks after randomization was significantly lower in the CRP-guided group than in the control group (57% vs. 77%), yet clinical outcomes were similar in the two groups. In the CRP-guided group, antibiotics were pre- scribed for one third of the patients with CRP levels lower than 20 mg per liter, but approximately 90% of the patients with CRP levels of at least 20 mg per liter received an antibiotic prescription.


CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.


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