Antibiotic resistance, which transforms ordinary microbes into menaces that cannot be easily controlled, is exacting a growing toll on the human population. More than two million people in the U.S. develop drug-resistant infections each year and at least 23,000 of them die as a result. Yet most antibiotic resistant infections are only identified long after a patient has left the doctor’s office.
The diagnostic hitch is how long it takes for bacteria to grow in the laboratory. The standard method for identifying drug resistance is to take a sample from a wound, blood or urine and expose resident bacteria to various drugs. If the bacterial colony continues to divide and thrive despite the presence of a normally effective drug, it indicates the microbes are drug-resistant. The wait time for such answers, however, is typically between 16 and 20 hours.
New innovations in engineering are allowing scientists to speed up that diagnostic process by sidestepping the need to watch for bacterial division altogether. A novel approach involves observing how the structure of individual bacterial cells changes in response to such antibiotic exposure, and only takes three to four hours. This rapid test could help clinicians to more quickly identify the best antibiotic and switch patients over to the correct treatment course, the study’s lead author Sunghoon Kwon of Seoul National University wrote via e-mail. The new findings were published in the December 17 Science Translational Medicine.
Developing such diagnostic advances is exactly what the World Health Organization called for this year in a sobering global analysis of antibiotic resistance. In too many cases, WHO noted, available tests take too long to run so physicians forgo them and simply prescribe broad-spectrum drugs. Developing faster tests that would lead to more targeted drug treatments would be a crucial step to help safeguard medications, the report said. If the new method makes its way into treatment centers it would be a step in the right direction. “The ability to determine changes in the structure of the single cell makes this unique among rapid-type analyses and it is an optimistic sign that this could be the beginning of a new area of study,” says Stuart Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine.
As a matter of course, a clinician will typically prescribe a drug to treat a patient’s suspected infection but only receives definitive lab results confirming whether the clinician’s best guess was correct a day or two after the patient started taking the drugs. That delay causes patients to take too many unnecessary antibiotics and inches us ever closer to a world where essential treatments are no longer effective.
The new approach, one of several rapid-testing methods currently in the works from various research teams, hinges on two significant advances in lab technology: The first is the immobilization of single bacterial cells—fixing them in place to get a clear image without harming the cells. The second is the development of a microfluidic chip that better emulates the necessary environment in which certain bacteria can thrive and allows researchers to take high-resolution images of single cells. These innovations allow experts to gauge whether a sample is resistant or susceptible to drug treatment because specialists can scour images of those cells for specific changes in their structure.
For this study, the Korean research team tested strains of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus spp. against various antibiotic exposures and were able to discern in a few short hours which strains would respond to drugs. The ability to rapidly diagnose antibiotic resistance would be huge, and indeed if we develop a system to do this quickly and effectively, it really could be a game changer for antibiotic use,” says Arjun Srinivasan, associate director for Healthcare-Associated Infection Prevention Programs at the U.S. Centers for Disease Control and Prevention.
The new method may not work with every bacterial strain, the authors warn, so the morphological patterns of each new strain would need to be carefully scrutinized before use. But better tracking of antibiotic resistance and stricter prevention methods would be key tools to help thwart the growth of antibiotic resistance. Indeed, previous studies have found that improper prescribing is a significant driver of antibiotic resistance. Such resistance occurs naturally over time but overuse of drugs speeds up the process by adding extra selective pressure.
For all the promise of this and other tests that aim to speed up diagnosis, this technology will not be showing up in hospitals and clinics anytime soon because it requires tools that far exceed the capabilities of those found in a typical lab and significant financial investment. “This is not a test that labs can start doing tomorrow,” Levy says. “It’s much more elaborate than most laboratories would want to be.”