CRP Test Can Guide Antibiotic Use in COPD

Point-of-care C-reactive protein (CRP) testing conducted to inform antibiotic prescribing in patients with chronic obstructive pulmonary disease (COPD) exacerbations was associated with lower overall antibiotic use, and with no evidence of increased harm, according to U.K. researchers.

Fewer patients with acute COPD exacerbations in the CRP-guided treatment group were prescribed antibiotics at initial general medical practice consultation (47.7% vs 69.7% in the usual care group) and after the first month of follow-up (59.1% vs. 79.7%), reported Christopher C. Butler, MD, F.Med.Sci, of the University of Oxford in England, and colleagues.

Between-group differences in scores on the Clinical COPD Questionnaire (CCQ) during follow-up were not clinically meaningful, suggesting that lower antibiotic use in the CRP-guided arm did not impact patient-reported, disease-specific quality of life during the weeks following initial consultation, they wrote in the New England Journal of Medicine.

“The evidence from our trial suggests that CRP-guided antibiotic prescribing for COPD exacerbations in primary care clinics may reduce patient-reported use of antibiotics and the prescribing of antibiotics by clinicians,” the authors stated.

They noted that primary care physicians are the main prescribers of antibiotics for patients with COPD experiencing exacerbations, and that roughly half of patients living with COPD have one or more acute exacerbations of the disease annually, while approximately one in four patients have two or more exacerbations each year.

“More than 80% of these patients receive antibiotic prescriptions in the United States and in Europe,” they wrote. “Although many patients who have acute exacerbations of COPD are helped by these treatments, others are not.”

CRP is a well recognized biomarker for assessing COPD exacerbations that can readily be measured at the point of care, the researchers wrote. They hypothesized that CRP testing could reduce unnecessary antibiotic prescriptions for COPD exacerbations in the primary care setting.

They tested the theory in a study involving 653 COPD patients seeking treatment for acute exacerbations at 86 general practice offices in the U.K.

Clinicians were given guidance on how to interpret CRP test results, but they were also told that antibiotic prescribing decisions should be “based on a comprehensive assessment of likely risks and benefits, given a patient’s underlying health status and clinical features.”

Based on findings from a 2012 study of antibiotic efficacy in COPD exacerbations, the clinicians were told that antibiotics were unlikely to benefit patients with CRP levels <20 mg/L.

They were further told that antibiotics may benefit patients with CRP levels of 20 to 40 mg/L, “mainly, if purulent sputum is present,” and that treatment with antibiotics was likely to benefit patients with CRP levels >40 mg/L.

Two primary outcomes were assessed in the study: patient-reported antibiotic use within 4 weeks of study randomization and COPD-related health status, as measured by CCQ, 2 weeks after randomization.

“Since we would need to show both a reduction in antibiotic use and no worsening of COPD-related health status in order for us to consider the CRP point-of-care test to be effective, we designed this study to answer both questions,” Butler and colleagues wrote.

They reported that antibiotic use was lower in the point-of-care CRP testing group (57.0% vs 77.4%, adjusted odds ratio 0.31, 95% CI 0.20-0.47).

Also, at 2 weeks, the adjusted mean difference in CCQ score was −0.19 points (two-sided 90% CI −0.33 to −0.05) in favor of the CRP-guided group.

At initial consultation, fewer patients in the CRP-testing group were prescribed antibiotics (47.7% vs 69.7%, for a difference of 22.0 percentage points, adjusted OR 0.31, 95% CI 0.21-0.45). A similar difference of 20.6 percentage points favoring the CRP-testing group was seen at 4 weeks follow-up (adjusted OR 0.30, 95% CI 0.20-0.46).

The investigators concluded that the death of two patients in the usual care group within 4 weeks of study randomization was due to causes unrelated to trial participation.

In an accompanying editorial, Allan S. Brett, MD, and Majdi N. Al-Hasan, MBBS, of the University of South Carolina School of Medicine in Columbia, wrote that reducing the use of antibiotics in the COPD population may be associated with immediate benefits, such as reduction in Clostridioides difficile colitis risk, and more long-term benefits, including a reduction in multidrug-resistant bacteria colonization that can lead to pneumonia.

“In our view, the findings from this study are compelling enough to support CRP testing as an adjunctive measure to guide antibiotic use in patients with acute exacerbations of COPD,” they wrote. “Although acute exacerbations of COPD represent only a small fraction of the cases seen in primary care practices, point-of-care CRP testing has also been shown to reduce antibiotic prescribing for more common clinical presentations (e.g., suspected lower respiratory infections in patients without COPD). Thus, point-of-care CRP testing could potentially be applied more broadly.”

But “Whether primary care practices in the United States would embrace point-of-care CRP testing is another matter, given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement,” they added.