A New Role for C-Reactive Protein

AndreyPopov / iStock / Getty Images Plus

C-reactive protein (CRP), a biomarker of inflammation, could have a new role involving antibiotic stewardship in patients with acute chronic obstructive pulmonary disease (COPD). A British study found a noticeably lower incidence of antibiotic use in COPD patients measured for C-reactive protein (CRP) via finger prick test, in comparison with a control group. Researchers published their results in The New England Journal of Medicine. “Ours is the first trial of biomarker guided management of [acute exacerbation of COPD] in ambulatory care and has found an effect that should be practice-changing,” said its lead author, Chris Butler, BA MBChB DCH CCH MD FRCGP (Hon)FFPH FMedSci, in a statement.

COPD is prevalent in both the United States and in the United Kingdom. As of 2014, it was the third leading cause of death in the U.S. Approximately 6.4% of all Americans and 2% of adults in the U.K. have received COPD diagnoses. Clinicians often prescribe antibiotics for patients experiencing flare-ups, yet bacterial infections are often not the cause of these incidents. Researchers from Cardiff University, the University of Oxford, and King’s College London hypothesized that they could leverage a point-of-care CRP test to safely reduce antibiotic use in this patient population.

A previous trial showed the biomarker’s ability to predict antibiotic response. Researchers found that antibiotics mainly benefited those with a high CRP but had little benefit for patients with a low CRP (<20 mg/L r). “So, we considered that information about the CRP level, together with guidance that low CRP levels more or less rule out benefit from antibiotics, might help clinicians safely reduce antibiotic use,” Butler, a professor of primary care at Oxford, told CLN Stat. In other trials, he and his colleagues demonstrated that CRP-guided antibiotic treatment safely reduced antibiotics for people with acute cough.

The trial recruited 653 patients with a diagnosis of COPD from 86 general medical practices in the U.K., randomizing them into two groups: usual care alone or usual care guided by a CRP point-of-care finger prick test. Researchers looked at health status (as measured by a clinical COPD questionnaire) as well as patient-reported antibiotic use 2 and 4 weeks after randomization, respectively, to determine primary outcomes.

In the CRP intervention group 57% of patients were prescribed antibiotics for COPD flare-ups, 24% fewer compared with the usual care group (77.4%). “Importantly, this reduction in antibiotic use did not have a negative effect on patients’ recovery over the first two weeks after their consultation at their [general practitioner] surgery, or on their well-being or use of healthcare services over the following six months,” Butler said. He added, “This reduction is about twice the magnitude of that achieved by most antimicrobial stewardship interventions.” The researchers also found no evidence of detrimental effects on clinical outcomes—indicating that using fewer antibiotics did not harm patients.

Findings from this trial should lead to a more stratified approach to personalized care, in which only those patients needing antibiotics will receive them, Butler said. For clinical labs, this shows that CRP at the point-of-care, giving broad categories of results, “can now be done very cheaply with no need for equipment or calibration,” he added. Next steps for his team are to use point-of-care testing to better guide antibiotics for symptoms of urinary tract infections.

CRP testing could serve as a supplementary measure to guide antibiotic use in patients with acute COPD, based on the findings of this study, wrote Allan S. Brett, MD, and Majdi N. Al‐Hasan, MB, BS, in a related editorial. Given its ability to reduce antibiotic scripts for more common conditions such as non-COPD lower respiratory tract infections, “point-of-care CRP testing could potentially be applied more broadly,” they wrote. There is the caveat of whether U.S. primary care practices would embrace this test, however, “given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement.”

Some questions about COPD care remain unanswered from these findings, continued Brett and Al-Hasan. The study “only suggests a way to reduce antibiotic prescribing without compromising clinical outcomes. It does not establish which patients (if any) truly benefit from antibiotic therapy or which antibiotics are most appropriate for COPD exacerbations. Additional clinical trials will be necessary to address these uncertainties,” they wrote.