18-19 - ANTIMICROBIAL RESISTANCE: The fight against antimicrobial resistance

As wildfires and record-breaking temperatures swept across European nations this summer, more people came to see climate change not as a future threat but as a dangerous reality. In the same way, antimicrobial resistance should be regarded not so much as a ‘ticking time bomb’ as a critical present-day pandemic.

Up to half of pathogens causing surgical site infections and over a quarter of those causing infections after chemotherapy are already resistant to standard prophylactic antibiotics in the USA. Antimicrobial resistance has already rendered seven types of antibiotics effectively useless against gonorrhoea, and in the last few years certain strains have developed resistance to the one remaining treatment option. According to the World Health Organization, a strain of gonorrhoea that can entirely evade remaining treatment options is ‘inevitable.’

Isoniazid and rifampicin were effective against tuberculosis for decades, but today 3.7% of new cases and 20% of previously treated cases are believed to be caused by strains resistant to them. Only half of multidrug-resistant tuberculosis is effectively treated with existing drugs. The antibiotics that all but eradicated tuberculosis from Europe have lost their potency, leaving the world vulnerable to a disease that still infects ten million people a year and is already the second leading infectious killer after COVID-19.

Several common respiratory diseases, including Streptococcus pneumoniae and Haemophilus influenzae, show reduced susceptibility to several classes of antibiotics. Despite the fact that most respiratory tract infections (RTIs) are viral, they account for the majority of general practitioners’ antibiotic prescribing in all health economies. As there is a direct relationship between antibiotic use and the development of resistance, over-use of antibiotics, which is the leading cause of antimicrobial resistance, must be dramatically reduced if we are to avoid a surge of untreatable infectious diseases.

Point of care CRP tests are one of the most effective tools we have against unnecessary antibiotic prescribing in primary care. LumiraDx’s diagnostic platform offers an accurate measurement of CRP within four minutes of a finger prick so that a clinician can reach an informed decision in the space of the first appointment. Many Northern European countries that use CRP tests as standard in primary care have markedly lower levels of resistant respiratory tract infections. Indeed, resistant Klebsiella pneumoniae ranges from less than 10% in Denmark and Sweden to over 50% in 18 other European countries.

Point of care CRP testing has demonstrated its efficacy in a number of pilot projects in the UK. In a study we led in the north west of England, 63% of patients who would have received an antibiotic prescription had a CRP blood level of less than 5 mg/l, and subsequently did not receive a prescription. Additionally, we undertook a major review of all the evidence around the use of CRP testing in patients presenting with RTIs in primary care, incorporating thousands of patients and dozens of clinical trials. There is an overwhelming amount of data showing that this technology reduces unnecessary antibiotic prescribing and thus slows the spread of antimicrobial resistance.

C-reactive protein point-of-care testing (CRP POCT) is also popular among both primary care professionals and their patients. Clinicians involved in the recent Primary Care Respiratory Society trial reported that it enhanced their confidence in antibiotic prescribing decisions. The test result helps to reassure patients, who arrive expecting antibiotics, that they have been diagnosed correctly and will avoid an ineffective treatment that could interact with their medicines or cause serious adverse drug reactions.

The main barriers to uptake in primary care appear to be financial constraints and lack of incentives to invest in new diagnostic processes. Yet failing to take up the new technology is proven to be a false economy. According to the Primary Care Respiratory Society, the cost per quality-adjusted life-year (QALY) gained at 6 months is £15,251,39, significantly less than the threshold of £20,000 to £30,000 per QALY that the National Institute for Health and Care Excellence (NICE) uses to measure cost-effectiveness of new drugs. Practices can make further cost savings by investing in a platform that can test for other biomarkers as well as CRP.

LumiraDx’s platform can give lab-comparable results for D-dimer (thrombosis) and HbA1c (diabetes) on the same device and will one day have the capacity to test for over thirty common conditions, delivering even greater economies of scale.

CRP point of care testing is proven to be cost-effective, improves patient outcomes and reduces inappropriate antibiotic prescriptions that fuel antimicrobial resistance. The UK urgently needs to follow the example set by countries in Scandinavia and roll out point of care diagnostics as standard, not just in GP practices but in pharmacies, diagnostic hubs and nursing homes.

The Primary Care Respiratory Society has recently published a ‘pragmatic guide’ detailing how this can be achieved. The guide is based around two algorithms, one for infectious exacerbations (IE) of chronic obstructive pulmonary disease (COPD) (Figure 1) and one for respiratory tract infections that are not associated with COPD (Figure 2). A patient with a COPD exacerbation should firstly be tested to rule out COVID-19 and influenza and if the presentation suggests bacterial infection, a point of care CRP test should then be performed.

The Primary Care Respiratory Society should be supported in its call for national guidance on the use of point of care CRP testing. Without a national standard set by NICE, the NHS could face ‘postcode diagnostics’ and potential differences in antimicrobial resistance patterns. It’s time to end this dangerous disparity and bring all regions up to the highest level.

Without decisive action, antimicrobial resistance is expected to cause ten million deaths each year by 2050 and reduce global GDP by 2% to 3.5%. Such a catastrophe is avoidable only if we maximise the potential of the latest technology and make point of care CRP testing standard practice.

Professor Jonathan Cooke has spent over 35 years in the NHS, including as Director of Research and Development and Director of Medicines Management at the University Hospital of South Manchester.

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