The results of a multisite, randomized controlled trial show that C-reactive protein (CRP) point-of-care testing resulted in decreased antibiotic prescribing for patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD), with no evidence of harm.
The authors of the study say the findings, published today in the New England Journal of Medicine, suggest that CRP testing, which measures the level of a protein produced by the liver in response to inflammation, can help clinicians avoid unnecessary antibiotic prescribing for a condition that is frequently treated with antibiotics, despite evidence that they aren't always needed.
"The evidence from our trial suggests that CRP-guided antibiotic prescribing for COPD exacerbations in primary care clinics may reduce patient-reported use of antibiotics and the prescribing of antibiotics by clinicians," the authors write.
Clinical criteria not enough to rule out antibiotics
For the trial, a team led by investigators from the University of Oxford and Cardiff University recruited patients over the age of 40 from 86 general medical practices in England and Wales who consulted a clinician for sudden worsening of symptoms of COPD—a group of lung conditions that cause breathing difficulties.
Acute exacerbations of COPD are marked primarily by three symptoms: extreme shortness of breath, a large increase in sputum production, and a change in sputum appearance. The condition can be triggered by viral or bacterial infections, but also by environmental pollutants or other irritants.
Antibiotic prescribing for acute exacerbations of COPD is generally based on patients having at least two of the three main clinical symptoms, but these symptoms can be subjective and aren't considered accurate enough to determine which patients can be treated safely without antibiotics. The investigators wanted to see whether CRP point-of-care testing could help clinicians with that decision.
The patients were randomly assigned 1:1 to receive either usual care or usual care guided by CRP point-of-care testing. Guidelines for interpretation of CRP test results suggest that antibiotics are unlikely to be beneficial for patients with a CRP level of lower than 20 milligrams per liter (mg/L), may be beneficial for those with a CRP level of 20 to 40 mg/L, and are likely to be beneficial for those with a CRP level higher than 40 mg/L.
The two primary outcomes in the study were patient-reported antibiotic use within 4 weeks after randomization and COPD-related health status at 2 weeks after randomization, as measured by patient responses to the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD status) to 6 (very poor COPD status). The investigators also reviewed data from electronic medical records to determine antibiotic prescribing during the initial consultation and over the first 4 weeks of follow-up.
A total of 649 patients underwent randomization, with 325 in the CRP-guided group and 324 in the usual-care group. Data obtained from 537 patients showed that fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57% vs 77.4%; adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference on the Clinical COPD Questionnaire at 2 weeks was – 0.19 points (two-sided 90% CI, – 0.33 to – 0.55) in favor of the CRP-guided group. That finding, the authors explain, indicates that reduced antibiotic use in the CRP-guided group did not compromise disease-specific quality of life.
Review of the antibiotic prescribing decisions made by clinicians showed that 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%; aOR, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of consultation (59.1% vs 79.7%; aOR, 0.30; 95% CI, 0.20 to 0.46). A total of 158 antibiotic prescriptions were issued to patients in the CRP-guided group, and 234 were issued to those in the usual-care group.
Analysis of secondary outcomes—including the prevalence of potentially pathogenic organisms in sputum, healthcare use, COPD-related health status, and general health status at 6 months—found no significant differences between the two groups. Two patients in the usual-care group died within 4 weeks of randomization, but the causes were considered to be unrelated to the trial.
'Compelling' evidence
In an editorial that accompanies the study, Allan Brett, MD, and Majdi Al-Hasan, MBBS, of the University of South Carolina School of Medicine, say the results of the trial are "compelling enough to support CRP testing as an adjunctive measure to guide antibiotic use in patients with acute exacerbations of COPD."
They note, however, that the findings only suggest a way to reduce antibiotic prescribing without compromising clinical outcomes, but they don't establish which patients truly benefit from antibiotics, or which antibiotics are most appropriate for treating acute exacerbations of COPD.
"Additional clinical trials will be necessary to address these uncertainties," they write.
See also:
Jul 11 N Engl J Med abstract
Jul 11 N Engl J Med editorial
