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Genetic methods cannot yet confirm antimicrobial susceptibility
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Experts from the European Committee on Antimicrobial Susceptibility Testing, or EUCAST, report that genetic testing is not yet advanced enough to verify whether an infection is susceptible to a specific antibiotic.
The committee, comprising a dozen experts, is responsible for setting breakpoints and offering guidance on phenotypic antimicrobial susceptibility testing. Although genetic testing is not ready to replace current methods for determining a pathogen’s susceptibility, they did acknowledge that there have been breakthroughs in whole genome sequencing (WGS).
“We chose to tackle this task on a ‘by organism’ basis, with particular focus on the use of technology for characterizing cultured isolates of bacteria that have been identified as critical [antimicrobial resistance] threats by the World Health Organization,” Matthew J. Ellington, DPhil, from the Antimicrobial Resistance and Healthcare Associated Infections Reference Unit at Public Health England, and colleagues wrote in their report. “There are encouraging signs, but our report makes clear that more robust data are needed across these diverse ‘bug/drug’ combinations.”
A EUCAST subcommittee analyzed the most current published evidence of using WGS as a tool for antimicrobial susceptibility testing. The researchers compared how WGS can calculate whether the organism belongs to the wild type (without resistance mechanisms) with the same prediction performed using epidemiological cut-off values that were developed by EUCAST. They discussed how to extend this to clinical breakpoints.
Neil Woodford, of Public Health England, presents the EUCAST report to colleagues at ECCMID 2016 in Amsterdam. Experts determined that whole genome sequencing is not yet advanced enough to determine if a pathogen is susceptible to antibiotics.
Source: ESCMID
Because there is currently no way to measure the accuracy of different WGS laboratories, the subcommittee emphasized the urgency to establish a single public database of all known resistance genes within different bacterial species to share and compare data more easily. They added that WGS technology cannot be used to analyze specimens directly; bacteria can only be sequenced after they have been cultured, which leads to time delays and additional cost that most labs cannot afford.
Although researchers did not rule out the possibility of a single assay predicting how a species of bacteria will respond to a specific antimicrobial drug, the evidence suggests we will not reach this point soon.
In an accompanying editorial, Gunnar Kahlmeter, EUCAST’s technical data coordinator and professor at the Central Hospital in Växjö, Sweden and Derek Brown, scientific secretary at EUCAST, wrote that phenotypic susceptibility testing will be replaced by genetic methods only if the genetic methods can predict resistance and susceptibility and quantitate the degree of resistance. This kind of prediction, they added, is becoming increasingly more difficult “as multiple resistance mechanisms become more common, and more of a concern as extreme resistance and pandrug resistance becomes a reality.”
To expand our current knowledge and develop more sophisticated prediction tools, EUCAST recommends that whole-genome sequencing be made a top priority in funding and research. The researchers concluded that unravelling the genetics of bacterial interactions with antimicrobials will become more difficult, but even more necessary as the bacteria continue to develop multiple resistance mechanisms.
“We will need more powerful bioinformatics tools in [the] future if we seek to make inferences about antimicrobial susceptibility based on combinations of multiple different genes or contributory mutations,” Ellington and colleagues wrote in their report. “If WGS data could be correlated directly with outcome, then this revolutionary tool might aid development of improved criteria for interpreting phenotypic data.” – by Savannah Demko
Disclosure: Please see the full report and full editorial for a list of all authors’ relevant financial disclosures.
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