C-reactive protein tests help curb antibiotic use in acute COPD

2019 05 08 23 39 6217 Lab Crp Test 400

Point-of-care testing for the inflammatory marker C-reactive protein (CRP) helped reduce the use of antibiotics for acute cases of chronic obstructive pulmonary disease (COPD), without an apparent knock on health outcomes, in a prospective U.K. study published in the July 11 issue of the New England Journal of Medicine.

In the open-label, randomized study of 653 patients treated in the primary care setting for acute exacerbations of COPD, the rate of self-reported antibiotic use in those whose management was guided by CRP tests was 57%, compared with 77.4% for those managed as usual. The study was led by Dr. Christopher Butler, clinical director of the University of Oxford Primary Care Clinical Trials Unit (N Engl J Med, July 11, 2019, Vol. 381:2, pp. 111-120).

Health-related quality of life as measured by scores on the Clinical COPD Questionnaire favored the CRP-guided group, and there were no notable differences in safety judging by rates of adverse events, among other measures.

"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," wrote Butler, who is also director of the U.K. National Institute for Health Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative, and colleagues.

Avoiding unnecessary prescriptions

The misuse of antibiotics poses many well-known dangers, including the emergence of antimicrobial resistance and treatment-related adverse events -- and it's an issue that crops up in COPD, which is diagnosed in 6.4% of the U.S. population and 2% of the adult population in the U.K.

In the U.S. and Europe, approximately 80% of people who have acute exacerbations for COPD wind up getting antibiotics, and while this helps many patients, others get no benefit, Butler et al noted in the NEJM report.

"Primary care providers are responsible for the majority of antibiotic prescriptions, and the highest overall number of such prescriptions are issued by family physicians," they wrote. "There is reason to believe that many of these prescriptions could be avoided."

In studies, point-of-care CRP testing has been shown to influence the prescribing of antibiotics for respiratory tract infections generally, but data for patients with acute exacerbations of COPD specifically have been limited, the authors noted.

Typically, healthcare professionals assess whether patients need antibiotics based on clinical symptoms, including shortness of breath, the amount of sputum, and sputum purulence. Government organizations are encouraging point-of-care testing for acute infections as a more objective measure of a patient's condition to improve the appropriateness of antibiotic prescribing; however, in studies that have been done, the effects on patient outcomes have for the most part not been assessed.

Getting up to speed on CRP

The NEJM study assessed the use of CRP as a tool for guiding COPD management in patients seen at 86 medical practices in England and Wales. Those in the CRP-guided arm were tested using Abbott's Afinion desktop devices for CRP point-of-care testing. The study was funded by the NIHR Health Technology Assessment Programme.

Per guidelines from the U.K. National Institute for Health and Care Excellence and the Global Initiative for Chronic Obstructive Lung Disease, clinicians involved in the study were advised that antibiotics are unlikely to help patients if CRP is less than 20 mg/L. For those with CRP levels between 20 mg/L and 40 mg/L, antibiotics may help if increased cough and purulent sputum is present, while those with levels greater than 40 mg/L are likely to benefit from treatment, according to the guidelines.

Patients randomized to CRP-guided treatment were tested for CRP at their initial visit with a healthcare professional. Those in the comparator group were tested in accordance with usual care and most never received a CRP test. The primary outcomes were superiority versus usual care for self-reported use of antibiotics four weeks after randomization and inferiority versus usual care on the 10-item COPD quality-of-life questionnaire two weeks after randomization.

The researchers placed a strong emphasis on the self-reported intake of antibiotics because they believed this was more likely to give a real-world picture of actual use (for example, patients don't always fill prescriptions, and some get drug samples). However, they also tallied the number of antibiotic prescriptions using patient records.

A face-to-face consultation was done four weeks after the initial consultation. Additionally, Butler and colleagues asked patients to fill out a Chronic Respiratory Questionnaire Self-Administered Standardized (CRQ-SAS) after six months.

Antibiotic prescribing rate lower in CRP group

In the CRP-guided group, the median CRP level was 6 mg/L, and 76% of participants in this cohort had a CRP level of less than 20 mg/L. Fewer than 1% of participants in the usual care group wound up having a CRP test.

In addition to the reduction in self-reported use at the four-week mark, the rate of antibiotic prescriptions given at the time of the initial consultation was much lower for those in the CRP-guided group than for those treated as usual (47.7% versus 69.7%). The same pattern was seen in the first four weeks of follow-up (59.1% versus 79.7%).

In both groups, most prescriptions for antibiotics were for a seven-day course. There were no clinically important differences between the groups when it came to the proportion who had potential pathogens or antibiotic-resistant bacteria in their sputum samples after four weeks, according to Butler and colleagues. The rates of hospitalization, diagnosis of pneumonia, and adverse events from antibiotics were all similar.

The similarity of Clinical COPD Questionnaire scores indicates that "less antibiotic use and fewer prescriptions from clinicians did not compromise patient-reported disease-specific quality of life," the authors reported.

Also, well-being at six months did not differ meaningfully, and primary and secondary healthcare utilization was similar.

"Awareness of receiving the point-of-care test may have contributed to enhanced COPD-related health status; however, this real-world effect needed to be captured because it may affect [healthcare]-seeking behavior, which is critical to assessments of overall benefit," Butler et al wrote.

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