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C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations

Butler CC, Gillespie D, White P, et al.

N Engl J Med 2019;381:111–20


Patients may be prescribed antibiotics for acute exacerbations of chronic obstructive pulmonary disease (COPD), however many exacerbations have a non-infective cause. C-reactive protein (CRP) tests detect circulating CRP produced by the body in response to infection, and could be used to guide antimicrobial prescribing. However, no studies have explored the feasibility of using CRP tests to guide antimicrobial prescribing for acute exacerbations of COPD.

In this study, Butler and colleagues investigated whether point-of-care CRP testing can reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of COPD.

In this multicentre, open label, randomised controlled trial, patients from across 86 general medical practices in England and Wales with a diagnosis of COPD were assigned to two groups. One group received usual care guided by CRP testing (CRP-guided group) and the other received usual care alone (usual-care group).

The first primary outcome measure was patient-reported-antibiotic use for an acute exacerbation of COPD within four weeks of randomisation and the second was COPD-related health status, as measured by the Clinical COPD questionnaire at two weeks after randomisation. The Clinical COPD Questionnaire is a 10-item scale with a score ranging from 0 (very good) to 6 (extremely poor). At six months, patients completed a standardised version of the Chronic Respiratory Disease Questionnaire (CRQ-SAS) and the European Quality of Life-5 Dimensions 5-Level questionnaire (EQ-5D-5L).

Of the 653 patients who underwent randomisation, fewer patients in the CRP-guided group reported antibiotic use than in the usual care group. (57.0% vs. 77.4%; adjusted odds ratio [OR], 0.31; 95% confidence interval [CI], 0.20 to 0.47) Scores on the Clinical COPD Questionnaire at two weeks were also 0.19 points (two-sided 90% CI, −0.33 to −0.05) lower in the CRP-guided group. Clinicians reported their antibiotic prescribing decisions in case report forms, with data ascertained for all but one patient regarding prescribing at the initial consultation, and 96.9% of patients for prescriptions over the first four weeks post-randomisation. Fewer patients in the CRP-guided group than the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%; OR 0.31; 95% CI, 0.21 to 0.45) and during the first four weeks of follow-up (59.1% vs. 79.7%; OR 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died during the four week study period from causes considered to be unrelated to the trial. At six month follow-up, there were no significant differences between the two groups on CRQ-SAS or quality of life scores.

CRP-guided prescribing of antibiotics for exacerbations of COPD resulted in a lower proportion of patients receiving antibiotic prescriptions from clinicians or reporting use of antibiotics, with no evidence of worsened health or quality of life outcomes. If implemented in practice, point of care CRP testing could optimise patient care and reduce the unnecessary prescription of antibiotics.

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