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New Phenotyping AST System a Useful Tool in Antibiotic Resistance Battle

JAN 31, 2019 | ALEXANDRA WARD
A next-generation phenotyping system is seeking to revolutionize antibiotic susceptibility testing (AST) in an effort to begin treating patients faster and to combat antibiotic resistance.

Developed by SeLux Diagnostics and detailed in a recent study in Scientific Reports, a scientific journal published by Nature, the new microplate-based surface area assay enables clinicians to prescribe targeted antibiotics up to 3 days faster than the current industry standard and also includes 60 different antibiotics in a single AST.

“We introduce a novel approach that allows phenotypic AST determinations for non-fastidious bacteria within 5 hours,” the investigators write. “After a 4-hour incubation in cation-adjusted Mueller-Hinton broth and antibiotic, this assay measures bacterial concentrations by binding a universal small-molecule amplifier to bacterial surfaces. Surface binding enables the method to account for bacterial morphological changes in response to antibiotics. Because this technique requires only a single, endpoint read, it should also enable larger antibiotic menus to be run for each patient sample.”

AST is not new; the technology has been around since the 1990s, but has not been modernized in years, explained Eric Stern, PhD, chief technology officer and co-founder of SeLux Diagnostics.

“[Although] revolutionary in their time, these automated platforms now fail to meet clinical needs in two critical dimensions,” Dr. Stern told Contagion®. “First, results arrive too slowly, and sample preparation requires too many days, to keep pace with cutting-edge ID techniques…Secondly, the antibiotic menus of conventional AST platforms are limited [and] tests can only be provided for 12-15 antibiotics at a time, which is insufficient to meet the demands of today’s resistant organisms.”
 
The AST constraints—namely, the long wait time—up until this point have led to clinicians using broad-spectrum therapies that can contribute antimicrobial resistance. Take sepsis, for example.

“Under the current paradigm of clinical care, septic patients are prescribed broad-spectrum antibiotics for a minimum of 3 days—and often 5 or more days,” Dr. Stern said. “This over-reliance on some of the best currently-available drugs directly fuels the rise of multidrug-resistant organisms.”

SeLux Diagnostics’ new AST assay seeks to close the gap between bacterial identification and AST.

“We sought to develop an assay that would enable rapid AST determinations but require only standard microplate processing hardware to perform,” David L. Smalley, PhD, president at American Esoteric Laboratories and a co-author of the Nature study, told Contagion®. “The surface area measurement concept provided the necessary accuracy. The small-molecule fluorescent probe provides the necessary signal amplification to enable the use of standard microplate readers, which should minimize costs and maximize throughputs.”

With this tool, health care providers will be able to personalize treatment plans by pinpointing specific antibiotics that will be most effective, Dr. Stern explained.

“Targeted antibiotics will not only more effectively kill the bacteria, but also lower the chance of it mutating and developing resistance,” he said. “In other words, the battle against superbugs can be improved with next-generation AST because patients will be transitioned to personalized, targeted therapies as quickly as possible.”

US Food and Drug Administration clinical trials are expected to begin in the second half of 2019, according to Dr. Stern.
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