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      C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

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          Abstract

          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).

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          Most cited references28

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial

            Objective To assess the effect of general practitioner testing for C reactive protein (disease approach) and receiving training in enhanced communication skills (illness approach) on antibiotic prescribing for lower respiratory tract infection. Design Pragmatic, 2×2 factorial, cluster randomised controlled trial. Setting 20 general practices in the Netherlands. Participants 40 general practitioners from 20 practices recruited 431 patients with lower respiratory tract infection. Main outcome measures The primary outcome was antibiotic prescribing at the index consultation. Secondary outcomes were antibiotic prescribing during 28 days’ follow-up, reconsultation, clinical recovery, and patients’ satisfaction and enablement. Interventions General practitioners’ use of C reactive protein point of care testing and training in enhanced communication skills separately and combined, and usual care. Results General practitioners in the C reactive protein test group prescribed antibiotics to 31% of patients compared with 53% in the no test group (P=0.02). General practitioners trained in enhanced communication skills prescribed antibiotics to 27% of patients compared with 54% in the no training group (P<0.01). Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days’ follow-up. Clinicians in the combined intervention group prescribed antibiotics to 23% of patients (interaction term was non-significant). Patients’ recovery and satisfaction were similar in all study groups. Conclusion Both general practitioners’ use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients’ recovery and satisfaction with care. A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care. Trial registration Current Controlled Trials ISRCTN85154857.
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              Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.

              Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                July 11 2019
                July 11 2019
                : 381
                : 2
                : 111-120
                Affiliations
                [1 ]From the Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford (C.C.B., E.R.), the Centre for Trials Research (D.G., J.B., R.L., E.T.-J., K.H., N.K.), the Division of Population Medicine (R.P., G.N., N.A.F.), and Wales Centre for Primary and Emergency Research, School of Medicine (M.G.), Cardiff University, the Specialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales (M.W.), Cardiff, and the School of Population Health and Environment...
                Article
                10.1056/NEJMoa1803185
                31291514
                791681c7-730f-4cfa-a0c0-dfdd8ffdb8f5
                © 2019

                http://www.nejmgroup.org/legal/terms-of-use.htm

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