CRP-guided antibiotic therapy for acute exacerbations of COPD: fewer prescriptions, similar outcomes
EBM Focus - Volume 14, Issue 18
Reference - N Engl J Med 2019 Jul 11;381(2):11
Patients with chronic obstructive pulmonary disease (COPD) suffer from an average of 1-2 exacerbations per year. Guidelines recommend using three criteria to determine if antibiotic therapy is warranted: worsening dyspnea, increasing sputum volume, and increasing sputum purulence. Antibiotics are typically prescribed when two (including sputum purulence) or three of these criteria are met. As patients and providers may have a difficult time assessing sputum purulence and volume, more objective data points could potentially help limit unnecessary antibiotic prescriptions.
An unblinded, multicenter trial in the United Kingdom randomized over 600 patients presenting to their primary care provider (PCP) with symptoms of an acute COPD exacerbation to either point-of-care C-reactive protein (CRP)-guided antibiotic therapy or usual care. Guidance was provided to clinicians for use of the CRP level (
< 20 mg/L = antibiotics unlikely to be helpful, 20-40 mg/L = antibiotics helpful if purulent sputum present, > 40 mg/L = antibiotics likely helpful). Patients in both groups had similar baseline characteristics.The two primary endpoints were patient-reported antibiotic use for COPD at four weeks (superiority analysis) and COPD-related health status at two weeks (non-inferiority analysis) after randomization. In a modified intention-to-treat analysis that included all patients with outcome data, 57% of patients in the CRP-guided group reported antibiotic prescriptions compared to 77.4% of the usual care group (NNT=5). The results of the Clinical COPD Questionnaire to assess health status slightly favored the CRP-guided group (adjusted mean difference -0.19, 95% CI -0.33 to -0.05), showing that the clinical outcomes were not worse, even though fewer patients were treated with antibiotics. There was no difference in the rate of adverse events, including diagnosis of pneumonia or rate of hospitalization at 6 months. Subgroup analysis showed CRP-guided therapy was most significant for reducing antibiotic use in those patients with 2 or 3 COPD exacerbation criteria at baseline.
This study highlights the idea that subjective data may not be the best indicator of need for antibiotics among patients with an acute COPD exacerbation. Among patients meeting just one of the standard criteria, nearly 50% of patients received antibiotic therapy over the four week time period. The objective measure of CRP may help limit unnecessary antibiotic prescriptions for patients with acute exacerbations of COPD, particularly among patients who meet two or three standard criteria. The point-of-care CRP testing utilized in this study is not CLIA-waived and is not yet widely available, although this test takes only 2-4 minutes and is relatively inexpensive (about $1200 for the machine, $4.50 for each test strip in the United States). It may be worth encouraging your lab to obtain a point-of-care CRP testing device and using CRP to more objectively identify patients who are likely to benefit from antibiotics for COPD exacerbations, and by extension reduce unnecessary antibiotic prescriptions.
For more information, see the topic Acute Exacerbation of COPD in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.