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Fighting Antibiotic Resistance Through CRP Testing

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A report commissioned by the UK estimates that unless we take “urgent action 10 million people a year will die from drug resistant infections by 2050”.

What is Antibiotic Stewardship? 

Humans have been using some form of antibiotics for thousands of years. Ancient medicines used in Serbia, China, Greece, and Egypt dating back to over 2000 years ago contained antibiotic properties.

 

The implementation of antibiotic drugs in the 20th century marks one of the most significant developments in healthcare, contributing to saving a countless number of lives (1).

 

However, the irresponsible use and over prescribing of antibiotics has led to antibiotic resistance. Antibiotic resistance is when the harmful bacteria that would ordinarily be treated easily with antibiotics evolves to become resistant to their effects, resulting in serious infections with no treatments or cures (2).

A report commissioned by the UK estimates that unless we take “urgent action 10 million people a year will die from drug resistant infections by 2050” (1).

 

Here at Egoo Health, we believe that antibiotic resistance is one of the greatest health threats of the future. This is why we are dedicated to creating new solutions that contribute to the Antibiotic Stewardship initiative.

 

Antibiotic stewardship, also referred to as Antimicrobial Stewardship is a composition of principles that aim to reduce antimicrobial resistance through a more responsible use of antimicrobial treatments (3).

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It is estimated that 80% of antibiotic prescribing is carried out by general practitioners (GPs) and about half of these prescriptions are not done appropriately. 

Relationship Between CRP and infections.
You may have heard about C-reactive protein (CRP) as a potential biomarker for a host o
f different diseases (4-7)  but one of CRP’s most useful roles is indicating the presence of an infection.

 

CRP is a protein created by the liver that increases dramatically in response to infection, inflammation, and injury. It is an established marker for acute inflammation, but recent research suggests it actually contributes directly to the inflammatory response.

 

CRP works by activating the classical complement pathway, an immune response that recruits various immune cells and proteins to protect the body from pathogens and has been shown to have a protective effect against certain bacterial infections in animal models. Because of this, doctors have been able to use CRP measurements to determine if there is an active infection in their patients (8).
 

How can CRP be used to inform antibiotic usage?
Based on the clinical research, we are confident that CRP testing is the solution that we have been searching for to make Antibiotic Stewardship simple and accessible to all.

 

CRP has been the focus of many studies to see if it can inform antibiotic prescription and duration of use in a variety of different contexts, particularly for respiratory tract infections (9-11).  

 

One such study performed by Little et al., a multinational randomized controlled trial performed throughout Europe, explored the effectiveness of CRP testing on patients with respiratory tract infections in 246 practices with an overall sample of 4,264 patients.

 

The researchers found that doctors who were trained to use CRP testing to inform antibiotic prescribing had significant decreases in their prescribing rate. Another group of doctors in this study received only communication training on how to talk to patients about antibiotics. This group also saw a reduction in antibiotic prescribing.

 

However, a third group that received both communication and CRP training had an even greater reduction in antibiotic prescribing compared to the two other intervention groups and the control group.

 

In this particular study, the researchers did find slightly worse secondary outcomes (duration and severity of symptoms and increased hospitalizations) in the intervention groups versus the control group, however, the authors do not believe these factors outweigh the benefits of reducing antibiotic prescribing, namely “demedicalisation of self-limiting illness, reduced risk of antibiotic-associated side-effects, and reduced risk of antibiotic resistance” (9).

 

In fact, there can actually be quite a few rather immediate benefits to implementing Antibiotic Stewardship, apart from the long-term goal of reducing antibiotic resistance.

 

For example, in another paper, a review looking at over a hundred different studies using various Antibiotic Stewardship interventions including biomarker testing, researchers found that there was either a decrease or no change in mortality rates for infections and readmission rates after implementing Antibiotic Stewardship interventions, and there was a major cost reduction in hospital expenditures which was most dramatic in the European Union and UK (12)


There are also studies looking into CRP use in chronic obstructive pulmonary disease (COPD) and gram-negative bacteria infections that, although they have different reference ranges and methods, were able to successfully reduce either antibiotic prescription or its duration of use (13-15).

 

As mentioned previously, there are numerous studies looking at the use of CRP with different kinds of infections, only a few of which are mentioned in this article. 

Telemedicine has become more popular than ever in recent years, and we believe that at-home quantitative biomarker testing can play a critical role in the success of these virtual visits.

Point-of-Care (POC) Testing and Antibiotic Stewardship
CRP testing is not just relevant in the hospital setting, but also in the primary care sector. It is estimated that 80% of antibiotic prescribing is carried out by general practitioners (GPs) and about half of these prescriptions are not done appropriately (16).

 

To help address this issue, some GPs have already successfully integrated POC CRP testing into their offices to help guide their antibiotic prescribing, whether that is for identifying infections, or using the concrete data provided by CRP measurement to reassure the patient of their health plan (11,16).

 

CRP POC testing is also effective at reducing antibiotics prescribing in another very high prescription setting, nursing homes (17)


We have talked a lot about how CRP testing can be used in a clinical setting, but here at Egoo Health, our vision has always been to take the burden off the healthcare system by moving biomarker testing into the home, empowering people to take responsibility for their own health, and encouraging greater collaboration between health professionals and patients.  

 

Telemedicine has become more popular than ever in recent years, and we believe that at-home quantitative biomarker testing can play a critical role in the success of these virtual visits.

 

Imagine patients having a CRP test in their homes that is simple enough that they can administer it on their own, receiving results in a matter of minutes.

 

This relieves the need to commute to the doctors' office and  provides valuable, personalized health data to inform the consultation, without the laboratory waiting time.

 

With guidance from their doctor, patients can be sent home with antibiotics and easily identify the proper duration of treatment by using at-home CRP testing.

Similarly, in nursing homes where antibiotics are frequently prescribed, POC testing can guide antibiotic use, lower costs, reduce antibiotic resistance, and ultimately, save lives without ever having to leave the home.

 

The ability to take quality biomarker testing technology and place it into new settings and contexts is one of the most powerful things about POC tests. No labs or laboratory experts needed, and no long wait time for results.

 

This is the future of healthcare that, thanks to POC testing, is becoming a reality sooner than we could have imagined. 

Online Medical Consultant

As with all research, the studies mentioned in this article are not without their limitations, however CRP use for Antibiotic Stewardship looks very promising.

 

Antibiotic use must be modified and managed responsibly, and it is essential that we weigh the limitations of new interventions against the cost of doing nothing and continuing to contribute to the global health threat of antimicrobial resistance.

 

It is important to note that CRP might be more useful with certain conditions than others, and individual characteristics such as visceral fat accumulation can affect CRP levels and should be taken into account as well (18).

 

Lastly, antibiotics can be lifesaving drugs and the use of them should be carried out with the close guidance of a doctor. Individuals should not stop taking prescribed medications without consulting a health professional beforehand, regardless of their CRP levels.

References 1. Hutchings MI, Truman AW, Wilkinson B. Antibiotics: past, present and future. Curr Opin Microbiol. 2019 Oct 1;51:72–80. 2.Antibiotic resistance [Internet]. [cited 2023 Feb 20]. Available from: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance 3.Shrestha J, Zahra F, Cannady J. Antimicrobial Stewardship. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Feb 20]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK572068/ 4.Avan A, Tavakoly Sany SB, Ghayour-Mobarhan M, Rahimi HR, Tajfard M, Ferns G. Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice. J Cell Physiol. 2018;233(11):8508–25. 5.Yu N, Cui H, Chen X, Chang Y. Changes of serum pentraxin-3 and hypersensitive CRP levels during pregnancy and their relationship with gestational diabetes mellitus. PLOS ONE. 2019 Nov 13;14(11):e0224739. 6.Cheng L, Zhuang H, Yang S, Jiang H, Wang S, Zhang J. Exposing the Causal Effect of C-Reactive Protein on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study. Front Genet [Internet]. 2018 [cited 2022 Jul 29];9. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2018.00657 7.Hart PC, Rajab IM, Alebraheem M, Potempa LA. C-Reactive Protein and Cancer—Diagnostic and Therapeutic Insights. Front Immunol [Internet]. 2020 [cited 2022 Jul 29];11. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.595835 8.Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018 Apr 13;9:754. 9.Little P, Stuart B, Francis N, Douglas E, Tonkin-Crine S, Anthierens S, et al. Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial. The Lancet. 2013 Oct 5;382(9899):1175–82. 10.Cals JWL, Butler CC, Hopstaken RM, Hood K, Dinant GJ. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. BMJ. 2009 May 5;338:b1374. 11.Martínez-González NA, Keizer E, Plate A, Coenen S, Valeri F, Verbakel JYJ, et al. Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: Systematic Review and Meta-Analysis of Randomised Controlled Trials. Antibiotics. 2020 Sep;9(9):610. 12.Nathwani D, Varghese D, Stephens J, Ansari W, Martin S, Charbonneau C. Value of hospital antimicrobial stewardship programs [ASPs]: a systematic review. Antimicrob Resist Infect Control. 2019 Feb 12;8(1):35. 13.Butler CC, Gillespie D, White P, Bates J, Lowe R, Thomas-Jones E, et al. C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations. N Engl J Med. 2019 Jul 11;381(2):111–20. 14.Prins HJ, Duijkers R, Valk P van der, Schoorl M, Daniels JMA, Werf TS van der, et al. CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions. Eur Respir J [Internet]. 2019 May 1 [cited 2023 Jan 16];53(5). Available from: https://erj.ersjournals.com/content/53/5/1802014 15.von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, et al. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Jun 2;323(21):2160–9. 16.Suttels V, Van Singer M, Clack LC, Plüss-Suard C, Niquille A, Mueller Y, et al. Factors Influencing the Implementation of Antimicrobial Stewardship in Primary Care: A Narrative Review. Antibiotics. 2023 Jan;12(1):30. 17.Boere TM, Buul LW van, Hopstaken RM, Tulder MW van, Twisk JWMR, Verheij TJM, et al. Effect of C reactive protein point-of-care testing on antibiotic prescribing for lower respiratory tract infections in nursing home residents: cluster randomised controlled trial. BMJ. 2021 Sep 21;374:n2198. 18.Iida M, Takeda S, Nakagami Y, Kanekiyo S, Nakashima C, Nishiyama M, et al. The effect of the visceral fat area on the predictive accuracy of C-reactive protein for infectious complications after laparoscopy-assisted gastrectomy. Ann Gastroenterol Surg. 2020;4(4):386–95.

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