CRP testing lowers antibiotic use in COPD exacerbations

By Gene Emery

NEW YORK (Reuters Health) - 10/7/2019

Testing for C-reactive protein (CRP) can reduce unnecessary antibiotic use in patients experiencing an exacerbation of chronic obstructive pulmonary disease (COPD), according to the results of a randomized clinical trial.

The test helped cut antibiotic use by 20% without affecting clinical outcome, they report in the July 11 issue of the New England Journal of Medicine.

Determining when to prescribe antibiotics in COPD patients has been a tough call for physicians. In the new study, known as PACE, doctors were advised that if the CRP level was below 20 mg/L, an antibiotic was unlikely to be beneficial. If it was above 40, an antibiotic would probably help. Between those two values, they were told, an antibiotic might help if the patient also has purulent sputum.

"The CRP test does not give you a yes-no answer. It gives you an indication of the body's reaction to an infection. So it provides another piece of information to be taken into account," chief author Dr. Christopher Butler of the University of Oxford, in the U.K., told Reuters Health by email.

Ultimately, 57.0% of patients whose doctors received information from the CRP finger-prick test reported taking an antibiotic compared with 74.4% in the usual-care group, a significant difference.

"We found no evidence of harm from reductions in antibiotic prescribing associated with testing," Dr. Butler said. "Reductions in antibiotic use therefore did not have a negative effect on patient's recovery over the first two weeks after their consultation, (or) on their well-being and use of health care services six months later."

"In our view, the findings from this study are compelling enough to support CRP testing as an adjunctive measure to guide antibiotic use in patients with acute exacerbations of COPD," Drs. Allan Brett and Majdi Al-Hasan of the University of South Carolina School of Medicine, in Columbia, write in an accompanying editorial. "Whether primary care practices in the United States would embrace point-of-care CRP testing is another matter, given the regulatory requirements for in-office laboratory testing and uncertainty about reimbursement."

They cautioned that, "The PACE study only suggests a way to reduce antibiotic prescribing without compromising clinical outcomes. It does not establish which patients (if any) truly benefit from antibiotic therapy or which antibiotics are most appropriate for COPD exacerbations."

Current guidelines suggest using increase dyspnea, increased sputum volume and increased sputum purulence as criteria for prescribing an antibiotic, but that metric isn't always reliable.

About 6.4% of Americans have been diagnosed with COPD. About 20% of acute exacerbations are not caused by an infection, and many may not be treatable with antibiotics.

The PACE study involved 653 patients treated at 86 general medical practices in England and Wales.

Among the volunteers who received the CRP test, 76% had a value below 20 mg/L, suggesting antibiotics would not be effective, 12% had a value of 20 to 40 and 12% had a value above 40.

An antibiotic was prescribed for 32.8% of patients in a CRP value below 20, 84.2% of patients with a value of 20 to 40 and for 94.7% of patients with a value over 40.

The rates of hospitalization during the six-month follow-up period were 8.6% with CRP testing and 9.3% without. Rates of pneumonia were 3.0% and 4.0% respectively.

"Less antibiotic use and fewer prescriptions from clinicians did not compromise patient-reported disease-specific quality of life," the researchers write. "Health care-seeking behavior or measures of patient well-being at 6 months did not differ meaningfully between the trial groups, nor did secondary clinical, microbiologic, disease-specific quality-of-life, or health care utilization outcomes with respect to primary and secondary care."

The study did not use sham CRP testing for the control group.

Whether CRP testing will save money is not clear, in part because most antibiotics are cheap, said Dr. Butler.

"We have to work out how best to take the possible downstream impact on antibiotic resistance into account," he said. "Antibiotic resistance is the 'global warming' of medicine - if we don't act now, we may waste this opportunity to help preserve the precious reservoir of antibiotic susceptibility for future generations. So it is not that helpful to compare just the cost of testing with the cost of antibiotics saved. Reducing unnecessary antibiotics for people with COPD will also reduce the selective pressure on organisms in people's lungs to become more resistant."


N Engl J Med 2019.

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