Moving diagnostic technology to the clinical setting is key to the fight against antibiotic resistance.

By Avishay Bransky, PhD

Scottish physician Alexander Fleming’s accidental discovery of penicillin in 1928 ushered in a new era of medicine. Finally, antibiotic drugs could provide effective treatments for high-mortality diseases including tuberculosis, polio, pneumonia, and syphilis. Reducing the threats posed by these and other illnesses was a major breakthrough of modern medicine. Antibiotics became widely available to the public in the 1940s and were hailed as “miracle drugs” by newspaper headlines and physicians alike. Over the next few decades, more than 20 novel classes of antibiotics were identified, but the rate of discovery has slowed drastically since then.1 With a decline in the discovery rate of new antibiotics, today’s approach for the development of new drugs to combat emerging pathogens is the modification of existing antibiotics. While antibiotics have been enormously effective in treating infections, the microorganisms that cause these diseases are constantly and randomly mutating. Periodically, a bacterium develops a mutation that makes it resistant to an antibiotic, and it survives the drug regimen prescribed to eliminate it. These remaining cells multiply, thus breeding drug-resistant bacteria. The ubiquity of these drugs threatens their utility, and by overprescribing and mismanaging their distribution, we risk making obsolete one of our most useful medical tools. Tuberculosis is a prime example of a disease that is becoming harder to treat. When patients terminate their treatments prematurely, for example, the surviving bacteria can be transmitted to other hosts, leading to multidrug-resistant TB strains that require a cocktail of multiple antimicrobial medications to cure. The problem is compounded when antibiotic drugs are administered to patients who don’t really need them. Mismanagement and overprescription of antimicrobials is accelerating the development of drug-resistant bacteria globally. The World Health Organization deems this a threat to global public health and reports that in many places, antibiotics are overused and misused in people and animals and often given without professional oversight.2 Studies have shown that treatment indication, choice of agent, or duration of antibiotic therapy is incorrect in 30% to 50% of cases.3,4 According to the Centers for Disease Control and Prevention, more than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.3

Current Testing and Diagnosis 

The fight against antimicrobial-resistant bacteria requires accurate, accessible, and immediate diagnostic tools. Several biomarkers can help differentiate bacterial and viral infections, yet no one biomarker alone is sufficient to accurately distinguish between the two types.  Usually, tests for a combination of several infection markers are required, but most of these tests need to be performed in well-equipped central labs and are not readily available within primary care. As a result, if a clinician suspects a bacterial infection, antibiotics are often prescribed on the spot. In some cases, the patient is told to wait for the results of the lab cultures before beginning treatment. However, once the drugs are prescribed, whether they are taken correctly is out of the clinician’s hands. Surprisingly, even in hospitals, which have modern labs, antibiotics are often misused: Studies show that 30% to 60% of the antibiotics prescribed in intensive care units are unnecessary, inappropriate, or suboptimal.4 

Pivoting to POC Diagnostics 

Apart from the discovery and development of new, more efficient classes of antibiotics, the greatest weapon against the mounting threat of antibiotic resistance lies in integrating innovative diagnostic technologies into clinical workplaces to help ensure that physicians can prescribe antibiotics only as appropriate. One of the most common tests that assists in diagnosing infection is a simple complete blood count (CBC). The result can help the physician to make a much more informed decision on antibiotics prescription. Despite the CBC being the most commonly performed blood test in the world, and one that can immediately inform clinical decision-making, it is still mostly restricted to the lab. Making this test accessible, inexpensive, and accurate at the point of care (POC) would improve clinical workflow and also facilitate correct diagnoses to reduce the number of extraneously prescribed antibiotics. Furthermore, pairing the CBC test with other already available POC tests for infection markers—such as a c-reactive protein or procalcitonin—would provide physicians an excellent tool to support clinical decision-making.

Stained white blood cells for differentiation of cell types. Pictured cells include neutrophil, lymphocyte, and monocyte. The middle cell is an immature granulocyte (abnormal cell may indicate illness). Courtesy, PixCell.

Stained white blood cells for differentiation of cell types. Pictured cells include neutrophil, lymphocyte, and monocyte. The middle cell is an immature granulocyte (abnormal cell may indicate illness). Courtesy, PixCell.

For a POC CBC test to become mainstream, however, the diagnostic instrument will need to be clinically validated in peer-reviewed scientific journals to deliver lab-grade results quickly and accurately. From a clinical practice perspective, ensuring that a new technology has gone through rigorous industry scrutiny is crucial so that providers can invest in the right equipment the first time, to arm themselves with the best tools to support clinical decision-making.  The POC test itself also needs to be very simple to perform, with as few steps as possible, and most importantly, that performance should not depend on an operator’s skill or experience. Most existing solutions or emerging technologies are still too complex to operate and maintain, while the preanalytical steps required might affect the results if not performed properly. With well-validated and robust tools, clinicians will better be able to gather immediate, accurate diagnostic results and significantly minimize the prescribing of unnecessary antibiotics. New technologies, such as artificial intelligence and machine vision, are now being incorporated into POC devices. These technologies utilize algorithms that are trained on hundreds of thousands of cells and different pathologies to an extent that greatly exceeds the capacity of the human mind and can enable more accurate clinical decision-making. Machine-vision algorithms can classify cells based on their morphology and a multitude of properties, providing higher resolution and clarity of different pathologies. Automatic sample processing is a must for POC testing because it eliminates a user’s preanalytical errors and ensures the repeatability of results each time a test is performed.

Looking Ahead

The state of healthcare today is one of old meeting new: fusing traditional practices and medications with cutting-edge technologies. Antibiotics have been a hugely important advancement in modern medicine, but caution must be exercised when prescribing them to avoid the potentially detrimental development of multidrug-resistant bacteria. Embracing innovative technologies—such as AI, machine vision, and POC devices—can support healthcare organizations and physicians in protecting the health and well-being of the populations and patients they serve. l

Avishay Bransky, PhD, PixCell.

Avishay Bransky, PhD, PixCell.

Avishay Bransky, PhD, CEO and co-founder of PixCell, is an expert in microfluidics and point-of-care testing, with extensive industrial experience in applied physics, software, and systems engineering. He is one of the inventors of the Viscoelastic Focusing technique, cell analysis methods and the microfluidic based cartridge. Bransky holds a BA in Physics, BSc in Materials Engineering, and a PhD in Biomedical Engineering, all from the Technion Israel Institute of Technology. References 1. Coates ARM, Halls G, Hu Y. Novel classes of antibiotics or more of the same? Br J Pharmacol. 2011;163(1):184–194. doi: 10.1111/j.1476-5381.2011.01250. 2. Antimicrobial resistance. World Health Organization. Updated July 31, 2020. Accessed August 7, 2020. 3. Biggest threats and data: 2019 AR threats report. Centers for Disease Control and Prevention. Reviewed June 18, 2020. Accessed August 7, 2020. 4. Luyt CE, Bréchot N, Trouillet JL, Chastre J. Antibiotic stewardship in the intensive care unit. Crit Care. 2014;18(5):480. doi: 10.1186/s13054-014-0480-6. Featured image: Red blood cells and white blood cells lined up on a single layer plane due to Viscoelastic Focusing phenomenon. Courtesy PixCell.