Finger-prick blood test to reduce antibiotics use in COPD patients

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COPDA simple finger-prick blood test for C-reactive protein can prevent unnecessary antibiotics for people with chronic obstructive pulmonary disease (COPD), according to a study by researchers from Cardiff University, University of Oxford and Kings College London.

With funding from the National Institute for Health Research (NIHR), the team demonstrated that using a CRP finger-prick blood test resulted in 20% fewer people using antibiotics for COPD flare-ups. 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 GP surgery, or on their well-being or use of health care services over the following six months.

Safely reducing the use of antibiotics in this way may help in the battle against antibiotic resistance.

More than 1m people in the UK have COPD, which is a lung condition associated with smoking and other environmental pollutants. People living with the condition often experience exacerbations, or flare-ups, and when this happens, three out of four are prescribed antibiotics. However, two -thirds of these flare-ups are not caused by bacterial infections and antibiotics often do not benefit patients.

Professor Nick Francis, from Cardiff University’s School of Medicine, said: “Governments, commissioners, clinicians, and patients living with COPD around the world are urgently seeking tools to help them know when it is safe to withhold antibiotics and focus on treating flare-ups with other treatments.

“This is a patient population that are often considered to be at high risk from not receiving antibiotics, but we were able to achieve a reduction in antibiotic use that is about twice the magnitude of that achieved by most other antimicrobial stewardship interventions, and demonstrate that this approach was safe.”

The finger-prick test measures the amount of C-reactive protein (CRP) – a marker of inflammation that rises rapidly in the blood in response to serious infections. People with a COPD flare-up who have a low CRP level in the blood appear to receive little benefit from antibiotic treatment.

Professor Chris Butler, from the University of Oxford, said: “This rigorous clinical trial speaks directly to the pressing issues of preserving the usefulness of our existing antibiotics; the potential of stratified, personalised care; the importance of contextually-appropriate evidence about point of care testing in reducing unnecessary antibiotic use, and; enhancing the quality of care for people with the common condition of chronic obstructive pulmonary disease.

Jonathan Bidmead, one of the patient representatives on the PACE study, commented: “We need to highlight not only how many people are saved by antibiotics but also that many are harmed though unnecessary antibiotic use. As a COPD sufferer, I know that antibiotics are routinely used at the first sign of an exacerbation: this study has shown that doctors can use a simple finger-prick test in a consultation to better identify those instances where antibiotics will probably do no good and may even do some harm. This can help us focus on other treatments that may be more helpful for some exacerbations.”

Professor Hywel Williams, director of the NIHR’s Health Technology Assessment (HTA) Programme, said: “This is a really important study which provides clear evidence that a simple biomarker blood test carried out in GP surgeries on people with chronic obstructive pulmonary disease experiencing flare-ups, has the potential to reduce unnecessary prescribing of antibiotics, without adversely affecting recovery from these flare-ups. This in turn helps tackle the wider global health hazards of antimicrobial resistance (AMR).

“The NIHR is committed to research in areas of greatest health need, such as AMR. This study is one of a number which we have funded over the last few years in this crucial area, in our sustained effort to tackle this worldwide threat.

Abstract
Background: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).
Methods: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).
Results: A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.
Conclusions: 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.

Authors
Christopher C Butler, David Gillespie, Patrick White, Janine Bates, Rachel Lowe, Emma Thomas-Jones, Mandy Wootton, Kerenza Hood, Rhiannon Phillips, Hasse Melbye, Carl Llor, Jochen WL Cals, Gurudutt Naik, Nigel Kirby, Micaela Gal, Evgenia Riga, Nick A Francis

Cardiff University material
New England Journal of Medicine abstract


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