Measurement of Circulating CRP Reduces Unnecessary Antibiotic Treatments

By determining levels of C-reactive protein (CRP) in the blood, it was possible to reduce the number of unnecessary prescriptions for antibiotics that were issued in the United Kingdom to individuals experiencing flare-ups of their chronic obstructive pulmonary disease (COPD).

CRP is an annular (ring-shaped), pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. This so-called acute phase response occurs as a result of increasing concentrations of interleukin 6 (IL-6), which is produced by macrophages as well as adipocytes in response to a wide range of acute and chronic inflammatory conditions such as bacterial, viral, or fungal infections; rheumatic and other inflammatory diseases; malignancy; and tissue injury and necrosis. These conditions cause release of IL-6 and other cytokines that trigger the synthesis of CRP and fibrinogen by the liver. CRP binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria. This activates the complement system, promoting phagocytosis by macrophages, which clears necrotic and apoptotic cells and bacteria.

COPD is lung condition associated with smoking and other environmental pollutants. Individuals with COPD frequently experience exacerbations, or flare-ups, and 75% of these cases are treated with antibiotics. However, about two-thirds of exacerbations are not caused by bacterial infections and antibiotic treatment is not indicated.

Investigators at Cardiff University (United Kingdom), University of Oxford (United Kingdom) and King's College London (United Kingdom) postulated that point-of-care testing of circulating CRP levels would be a way to reduce unnecessary use of antibiotics without harming patients who experienced acute exacerbations of COPD.

The investigators performed a multicenter, open-label, randomized, controlled trial involving 653 patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at one of 86 general medical practices in England and Wales for an acute exacerbation of COPD.

Results revealed that by using a CRP finger-prick test to identify patients with low CRP levels in the blood made it possible to reduce the number of patients receiving antibiotics for COPD flare-ups by 20% without having a negative effect on patients' recovery over a period of more than six months.

Senior author Dr. Nick Francis, senior clinical research fellow at Cardiff University, said, "Governments, commissioners, clinicians, and patients living with COPD around the world are urgently seeking tools to help them know when it is safe to withhold antibiotics and focus on treating flare-ups with other treatments. This is a patient population that are often considered to be at high risk from not receiving antibiotics, but we were able to achieve a reduction in antibiotic use that is about twice the magnitude of that achieved by most other antimicrobial stewardship interventions, and demonstrate that this approach was safe."

The CRP study was published in the July 11, 2019, online edition of the journal New England Journal of Medicine.

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Cardiff University
University of Oxford
King's College London