How point of care C-Reactive Protein (CRP) testing could revolutionize antibiotic prescription
The over-prescription of antibiotics in primary care, especially for respiratory issues, causes a multitude of respiratory problems across the globe – not least the growing danger of antimicrobial resistance (AMR). But what if there was a rapid, accurate point-of-care (POC) test that could rule out serious illnesses like pneumonia and help GPs be better antimicrobial stewards?
In this webinar, Dr. Rogier Hopstaken outlines how his research into point of care C-Reactive Protein (CRP) testing could show us the way forward.
Alarming reports about the global issue of antimicrobial resistance (AMR) show that failure to act could result in 10 million deaths by 2050 – higher than projected deaths from cancer—and cost £66 trillion.1
AMR is not just a future problem, either. 2019 saw 1.27m deaths directly attributed to bacterial AMR, and a total of 4.95m deaths associated with bacterial AMR.2
Could rapid diagnostic testing be a way to turn the tide? The Review on Antimicrobial Resistance—commissioned by the UK Prime Minister to investigate into solutions to tackle drug resistance on internationally—believes so. It identifies rapid diagnostics as key to tackling AMR, by reducing the huge number of unnecessary antibiotic prescriptions—of the 40m antibiotic prescriptions for respiratory issues in the US every year, 27m are unnecessary.3
However, as Dr. Hopstaken remarks, life for a primary care physician can be hectic. Time is stretched, attention often has to be switched at a moment’s notice, and there can be much diagnostic uncertainty, especially with respiratory issues in their early stages. An antibiotic prescription for a patient presenting with respiratory issues can seem a tempting, easy solution.
Chest radiography is one method to diagnose respiratory issues. But it’s not always that helpful—Hopstaken’s own research uncovered significant disagreement: 40% in moderate pneumonia radiography results.4
To find the answer, Dr. Hopstaken and his team studied all possible predictors of pneumonia in primary care. They found that the C-reactive protein (CRP) biomarker was by far the strongest predictor, especially when added to a patient’s history and a physical exam. When the CRP result is low (<20mg/l), you can exclude pneumonia as a diagnosis.5
They tested their CRP hypothesis in a cluster randomized controlled trial, alongside a second intervention they called Enhanced Consultation Skills. This included refreshing the participating physicians’ knowledge on lower respiratory tract infection (LRTI), alongside training in communication skills, to help them better understand the patient’s questions, needs and requests.
The result of CRP POCT demonstrated 25%-30% reduction in unnecessary antibiotic prescription.6-9 This percentage was even higher when combined with improved communication.10 The results were reinforced when the study was recreated on a pan-European scale.9 In 2019, the trial was recreated on vulnerable patients with chronic obstructive pulmonary disease (COPD), which found a 20% reduction in antibiotic prescription,11 and more recently a nursing home setting—where POCT is not routinely performed—found a significant reduction of >25% in antibiotic prescriptions.12 Research is also beginning to demonstrate that there is value in CRP testing on children, too.13
On top of this, Dr. Hopstaken has collected much qualitative and quantitative data suggesting that patients and professionals alike are highly satisfied with using CRP POCT.
CRP POCT is recommended in moderately ill patients where there is diagnostic uncertainty around respiratory infection.
Dr. Hopstaken gives examples of how his own practice has changed by CRP testing. One elderly patient with COPD, who is often prescribed antibiotics when presenting with dyspnea, crackles and rhonchi, is tested and shows 11mg/l CRP. He didn’t need antibiotics after all.
Conversely, a younger patient with a dry cough and normal auscultation—who wouldn’t be prescribed antibiotics ~80% of the time—showed 145mg/l of CRP. Thanks to the test, he got the antibiotics he needed.
As Dr. Hopstaken mentioned, primary care physicians are under a lot of pressure. So, a diagnostic solution for POC would need to help rule out serious infection and diagnose pneumonia in a way that is accurate and doesn’t disrupt their routine.
The research team tested a range of CRP POC devices. Both the highly effective and less effective devices proved clinically useful for helping to diagnose pneumonia and reduce unnecessary antibiotic prescription.14,15
However, Dr. Hopstaken notes that it’s not realistic to just simply drop a CRP POC testing device into primary care clinics. Quality assurance must be taken into account; something many GPs don’t often consider. Factors such as how samples are collected and how the device is stored and used all impact the quality and reliability of results.
Strangely, many guidelines don’t mention or recommend CRP POCT—for example the World Health Organisation, in Antimicrobial Stewardship Interventions: A Practical guide, neglects CRP altogether.
But if the results are so encouraging for this well-established and rapid test, why is it left out?
Dr. Hopstaken believes that common misunderstandings about CRP tests are to blame. While CRP testing is known as being sensitive, it is also known as being non-specific. But this is not true. Actually, in the hands of care professionals who want to diagnose severity of illness, CRP is a very specific marker.
Another obstacle to CRP testing is the theory that it could lead to over-testing. But this too has been disproved. Over a 10-year testing period in the Netherlands, there were no signals of over-testing found. On average, a GP performed just 2-3 tests per week.
Though over-prescription of antibiotics is beginning to be addressed in areas like Scandinavia and The Netherlands, there is much work to do. Especially in southern Europe, South-East Asia and sub-Saharan countries, POCT is low and antibiotic over-prescription is rife.
Dr. Hopstaken conducted a study in Ethiopia into the potential impact of CRP. For acute cough patients, almost the only treatment available was antibiotics, prescribed 86% of the time.16
When Dr. Hopstaken ran CRP tests, the results mirrored Western Europe: 66.6% of patients had very low levels of CRP and did not need antibiotics. Which goes to demonstrate that countries like Ethiopia, with very high prescribing numbers, could benefit significantly from integrated CRP testing at primary care.
CRP POCT is now the standard for GPs in the Netherlands, and Dr. Hopstaken ends with a rallying cry for more boards and countries to consider integrating CRP POCT into their primary care facilities.
References:
The views and opinions expressed in this webinar are those of the speakers and do not necessarily reflect the views or positions of Roche or any other sponsors.
