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ID Genomics Genetic Fingerprinting Tech Detects Superbug as Firm Prepares Regulatory Filing

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NEW YORK (GenomeWeb) – Seattle-based ID Genomics said that it has used its genetic fingerprint technology to identify and track ballooning levels of a drug-resistant superbug, Escherichia coli ST1193.

Evgeni Sokurenko, founder of ID Genomics and a professor of microbiology at the University of Washington School of Medicine, said in an interview that this is the first notification of E. coli ST1193’s rise to pandemic proportions within the last six years. The new strain will not respond to ciprofloxacin, among the most frequently prescribed antibiotics to eliminate E. coli infections, but it responds to another antibiotic, cephalosporin, that's less frequently prescribed, he said.

Although it is an entirely different strain, the new bug is similar in ways to another known strain E. coli H30-Rx that's also a superbug, Sokurenko said. Researchers have seen that ST1193 is growing at a faster rate than H30-Rx, he said, and have witnessed a sevenfold increase in its prevalence since 2011, including a 35 percent increase in the past year in the US alone.

The firm combined both of its rapid diagnostic products in identifying the pathogen, Sokurenko said. The firm used a rapid diagnostic test, CloNet, which assigns unique microbial DNA fingerprints to reveal the clonal identity of a bacterial strain in patient samples. CloNet assigns barcodes to infecting bacteria in urine by detecting the presence or absence of seven single nucleotide polymorphisms via PCR.

These barcodes are associated with various bacterial strains and linked to antibiotic resistance profiles, Sokurenko said. The firm then matches barcodes with the content of BactNet, a database developed by the firm that links fingerprints identified by the rapid diagnostic test with bug responses to commonly prescribed antibiotics.

Healthcare professionals currently need at least two days to grow a culture and identify an optimal antibiotic. Using ID Genomics' test and database, though, clinicians can do this in about 30 minutes, Sokurenko said.

Each fingerprint link in the BactNet database tracks the medical history of different bacterial strains locally, nationwide, or globally. According to ID Genomics, the resource enables doctors to recommend the proper treatment plans quickly and accurately, which positively impacts patient health, reduces medical costs associated with repeat visits, and tempers the effects of antimicrobial resistance.

In June 2017, ID Genomics formed a national consortium of clinical partners, under a National Institutes of Health grant, with the objective of improving the speed and accuracy of infectious disease diagnostics and antibiotic treatment. The firm began working with its partners to record genetic fingerprints of antibiotic strains isolated from patients with active infections, and to characterize the strains' antibiotic susceptibility.

In all, ID Genomics has raised a total of $4 million, Sokurenko said. That includes funding from private investors in addition to the NIH grant, which is worth $3 million over three years.

Sokurenko noted that his firm expects to soon expand tenfold the number of partners supplying bacterial strains to the company's database. Labs worldwide will send the firm its pathogenic strains, and the firm will analyze them and assign genetic fingerprints that will enable clinicians to determine appropriate treatments when they encounter the strains in their clinical work.

He said that the firm intends to apply for clearance from the US Food and Drug Administration for use of its technology in a diagnostic test that hospital clinicians could use at a patient's bedside. Results from ongoing and future clinical studies will be used as part of the application process, and the firm hopes to have clearance in 18 to 24 months, he said. Meanwhile, the firm will continue to use the system for surveillance to track the location and prevalence of emerging superbugs with pandemic potential.

PCR-based clonotyping

In a study published in PLOS One last year, Sokurenko writing with colleagues noted that despite the known clonal distribution of antibiotic resistance in many bacteria, empiric antibiotic selection still relies heavily on species-level cumulative antibiograms.

The researchers described applying the ID Genomics PCR-based clonotyping assay to fresh urine samples to rapidly detect Ecoli and the urine strain's clonotype. They concluded that "antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic-pathogen mismatch" by 60 percent or more.

Michael Liss, director of clinical research and assistant professor in the department of urology at UT Health San Antonio, said in an interview that the use of antibiograms, which provide profiles of antimicrobial susceptibility of microorganisms to a battery of antimicrobial drugs, is a generic form of monitoring local antibiotic resistance trends. However, the use of CloNet and BactNet "could allow for more specific monitoring over time," he said, adding, "When we detect superbugs like ST1193 we can sound the alarm and create new rapid detection systems locally to combat infection risk."  

ID Genomics' technology could be used as an early detection system for superbugs, used in a similar manner to the monitoring of other deadly infections, Liss said. 

In a study published in January 2016 in Open Forum Infectious Diseases, Sokurenko and colleagues described use of single nucleotide polymorphisms-based typing of E. coli used for both epidemiological studies and clinical diagnostics.

They used a rapid clonotyping method for extraintestinal E coli based on detection of the presence or absence of seven SNPs within 2 genes, fumC and fimH. They used a reference set of 2,559 E coli isolates to predict the resolving power of the method and 582 representative strains from this set to evaluate the test's robustness.

The researchers noted that using quantitative PCR, they determined E. coli presence and septatype identity in urine specimens within 45 minutes with bacterial loads "as low as 102 colony-forming units/mL and, at clinically significant bacterial loads, with 100 percent sensitivity and specificity."

Finding a superbug

Five years ago, Sokurenko founded ID Genomics based on research he conducted with his team at the University of Washington. In identifying the E. coli ST1193 strain, the firm collaborated with the university and applied CloNet to quickly sort disease-causing bacteria into families identified by their genetic fingerprints. As part of a two-year initiative, the collaborators applied big data analytics to examine 11,000 bacterial strains isolated from patients with infections of blood, urine, bladder, or kidneys at nine medical centers. After applying genetic fingerprints to the bacterial strains, the researchers determined the pathogens' responses to 10 different antibiotics, and linked this to geographical and historic data, the firm said.

By applying the big-data tools, researchers discovered the rise of E. coli ST1193, which accounts for up to a third of the total bacterial resistance to ciprofloxacin, among the safest and most effective antibiotics in addressing healthcare needs, according to ID Genomics. The new superbug is also mostly resistant to another popular antibiotic, Bactrim, as well as to tetracycline.

In addition to continuing its development of a diagnostic platform with a view to obtaining US FDA 510(k) clearance, ID Genomics is planning to build a microbial surveillance network capable of monitoring infectious bacteria globally.

Awareness for the need for quicker methods of pathogen detection and antimicrobial susceptibility testing detection is growing.

To meet the provisions of the 21st Century Cures Act, signed into law in 2016, the FDA in December introduced an initiative designed to enable diagnostic companies and healthcare professionals to obtain important updates regarding breakpoints for antibiotics and antifungal drugs. Among the important outcomes of the FDA's initiative, companies developing antimicrobial susceptibility tests could be able to obtain regulatory clearance for their products more easily.

According to the Centers for Disease Control and Prevention, each year in the US, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a direct result of these infections. Early and aggressive action should be taken to keep germs with unusual resistance from spreading in healthcare facilities, the CDC said.

Antibiotic-resistant infection treatment costs in the US alone have doubled since 2002 and now exceed $2 billion annually, according to a study by researchers at Emory and Saint Louis universities. Antibiotic resistance added $1,383 to the cost of treating a patient with a bacterial infection, they said.