CRP testing may help guide antibiotic use for COPD exacerbations

Abstract

C-reactive protein (CRP)-guided prescribing of antibiotics in patients with an acute exacerbation of COPD resulted in fewer patients receiving antibiotics during the initial consultation and over the first 4 weeks of follow-up compared with those receiving usual care, according to results of the PACE study published in the New England Journal of Medicine.1Butler CC et al.N Engl J Med. 2019; 281: 111-120Crossref Scopus (91) Google Scholar In addition, the two groups had similar clinical outcomes. The cause of acute exacerbations of COPD may vary, with some triggered by bacterial respiratory infections and others by viruses. Unfortunately, it is difficult to determine which patients may benefit from antibiotics (i.e., those with bacterial infections) and which do not need them. Therefore, having a reliable biomarker that can be assessed in the clinic would be beneficial in reducing unnecessary antibiotic use in these patients. The PACE study was a multicenter trial in which 653 patients with an acute exacerbation of COPD (mean age 68.1 y, 51.6% male) were randomized to point-of-care CRP testing to help guide antibiotic prescribing (n = 325) or to usual care (n = 324).1Butler CC et al.N Engl J Med. 2019; 281: 111-120Crossref Scopus (91) Google Scholar The patients were enrolled from 86 general medical practices in the United Kingdom from January 2015 to February 2017. In the CRP-guided group, the guidance stated that for patients with a CRP level lower than 20 mg/L, antibiotics are unlikely to be beneficial and usually should not be prescribed. For those with a CRP level from 20 mg/L to 40 mg/L, antibiotics may be beneficial, mainly if purulent sputum is present; and for those with a CRP level higher than 40 mg/L, antibiotics are likely to be beneficial. Fewer patients in the CRP-guided group reported receiving antibiotics compared with those receiving usual care (57% vs. 77.4%), with comparable clinical outcomes between the two groups, according to the clinical COPD questionnaire given at 2 weeks. Overall, fewer patients in the CRP-guided group received antibiotics at the initial consultation (47.7% vs. 69.7%) or over the first 4 weeks of follow-up (59.1% vs. 79.7%). The 2019 GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines comment on the use of CRP to help guide antibiotic prescribing during COPD exacerbations.2https://goldcopd.org/wp-content/up-loads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdfGoogle Scholar The organization noted that study data on this biomarker have been contradictory, and CRP is elevated in both bacterial and viral infections, making it difficult to determine if antibiotics should be used. Therefore, GOLD stated that CRP should not be used to guide antibiotic use in patients with COPD exacerbations. Instead, GOLD highlighted data on use of procalcitonin, suggesting that this biomarker is more specific for bacterial infections and may be of greater value to help determine if antibiotics should be given to those with COPD exacerbations. Several studies have suggested that procalcitonin-guided antibiotic treatment reduced antibiotic exposure and adverse effects without affecting clinical outcomes. However, the majority of data is of low to moderate quality, and additional well-designed studies are needed to confirm the utility of this biomarker. GOLD recommends that antibiotics be given to patients with COPD exacerbations who meet any of these criteria: Patient has the three cardinal symptoms (increase in dyspnea, sputum volume, and sputum purulence); patient has two of the cardinal symptoms if increased sputum purulence is one of them; or patient requires mechanical ventilation. Antibiotics are recommended to be given for 5 to 7 days, and the choice of therapy should be based on local bacterial resistance patterns. The organization noted that appropriately used antibiotics for COPD exacerbations can help shorten recovery time and reduce the risk of early relapse and hospitalization duration. In an accompanying editorial on the findings of the PACE study, the authors wrote, “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. 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.”3Brett AS et al.N Engl J Med. 2019; 281: 174-175Crossref Scopus (6) Google Scholar The PACE results need to be considered along with the GOLD guidelines. For now, symptomatic patients with COPD exacerbations should be treated appropriately until further studies can confirm the utility of CRP or procalcitonin.