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New Technologies, Regulatory Approvals Highlight Antimicrobial Resistance Testing in 2018

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NEW YORK (360Dx) – Antimicrobial resistance shot into the frontline of diagnostic testing in 2018 with a slew of regulatory approvals to bring new technologies to the market while diagnostic developers continued with their efforts to improve on existing methods.

Throughout the year, the US Food and Drug Administration cleared new tests used to help manage microbial resistance while companies pushed their technologies toward commercialization, and other industry players struck deals to commercialize their products and increase their adoption.

In hospitals and health systems, molecular testing is being increasingly used to quickly identify infectious disease organisms and to determine which drugs they may be resistant to, Karen Kaul, chair of the department of pathology and laboratory medicine at NorthShore University HealthSystem, said in an interview.

Clinical procedures vary depending on whether the hospital uses molecular testing to screen for organisms that have antimicrobial resistance or to diagnose specific pathogens and decide whether those pathogens are resistant to therapies, Kaul noted. For example, using PCR-based molecular assays for screening, NorthShore has driven the rate of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections to near zero, she said.

Not all antimicrobial testing is molecular, however, Kaul said, noting that new non-molecular and direct-from-blood methods are also being adopted.

One example of this, she said, is an automated, direct-from-sample platform that combines genotypic pathogen identification with phenotypic antimicrobial susceptibility testing, which was developed by Accelerate Diagnostics and was cleared in 2017 by the US Food and Drug Administration.

Further, T2 Biosystems recently announced that it completed a final milestone for development of a T2 gram-negative bacteria resistance diagnostic panel being advanced through a partnership with Allergan and supported by CARB-X, an investor in projects to combat antimicrobial resistance. The T2 panel could become the first direct-from-blood antimicrobial resistance panel.

Diagnostic companies are also marketing tests that help clinicians decide whether they should prescribe antibiotics at all for some conditions.

The National Institute of Allergy and Infectious Diseases has sponsored an ongoing clinical study to determine whether low levels of procalcitonin can reliably reveal whether a person’s lower respiratory tract infection will improve with antibiotics. Investigators at the NIAID-supported Antibacterial Resistance Leadership Group are collaborating in the PCT study with researchers and medical experts from BioMérieux, whose Vidas BRAHMS PCT assay was granted expanded-use clearance in 2017 by the FDA to help healthcare providers determine if antibiotic treatment should be started or stopped in patients with lower respiratory tract infections, and stopped in patients with sepsis.

The FDA noted at the time that the assay is the first to use procalcitonin, a protein associated with the body’s response to a bacterial infection, as a biomarker in helping make antibiotic management decisions in patients with LRTI.

"Respiratory infections are the leading cause of infectious disease deaths globally …. and that concern is on the minds of providers trying to decide whether to prescribe antibiotics," Ephraim Tsalik, the study's principal investigator, said in an interview. However, even with the existence of PCT and other biomarker tests, doctors still don't have tools that are robust enough to assess whether a patient clearly has a bacterial or viral infection, he said. Consequently, physicians frequently err on the side of caution and prescribe antibiotics even when a test tells them that antibiotics to fight bacterial infections are not needed.

As a result, researchers are focusing on alternate technologies in the hopes of developing higher performance tests. At Duke University, Tsalik's group has shown "that gene expression is a much more robust way to differentiate these types of infections than PCT," he said.

Three years ago, he cofounded a company called Predigen to develop a sample-to-answer test that measures host gene expression signatures to determine if antibiotics should be prescribed. Such a test could be on the market in around three years, and Predigen is working with diagnostic system developers to move it to commercialization, he said.

Similar to Predigen, Inflammatix is developing diagnostic tests that leverages multiplex gene expression to analyze a patient's immune system. The firm is developing a sepsis diagnostic test that could enable physicians to determine within one hour whether an infection is bacterial or viral, and help clinicians decide whether to prescribe an antibiotic.

Tests that aren't specifically for determining antimicrobial resistance are also being increasingly used by physicians to reduce antibiotic overprescription, Canaccord Genuity analyst Mark Massaro said in an interview, noting the uptake of Quidel's point-of-care Sofia 2 influenza immunoassay among doctors.

"If that test result is positive, a lot of physicians are comfortable ordering a Tamiflu script for their patients," and avoiding ordering unnecessary antibiotics, Massaro said.

FDA clearances

The past year saw a number of notable regulatory approvals and clearances for tests and systems addressing antimicrobial resistance and antibiotic overuse. In November, the FDA granted 510(k) clearance to BioMérieux affiliate BioFire Diagnostics for its PCR-based assay that detects 33 common pathogens causing lower respiratory tract infections. The pneumonia panel test detects 18 bacteria and eight viruses, as well as seven genetic markers of antimicrobial resistance. The Plus version of the panel detects the same 33 targets as well as the MERS-CoV virus.

The same month, Becton Dickinson announced it had received clearance for the BD Phoenix CPO test, which could help hospitals contain the spread of antimicrobial resistance by shortening the time to detect carbapenemase-producing organisms.

In May, Cepheid announced that the Xpert Carba-R test received clearance for expanded claims. The test can now be used on perirectal swabs and pure colonies. Carba-R detects five families of resistance genes from carbapenemase-producing Gram-negative bacteria.

And BacterioScan received FDA clearance earlier this year for its bacterial urinary tract infection testing platform.

Test funding

Along with regulatory nods for the technologies, funding for antimicrobial resistance testing initiatives remains robust.

In November, the Foundation for Innovative New Diagnostics, a Swiss nonprofit, launched a new initiative to address antimicrobial resistance, particularly in developing countries.

In May, MicrobeDx announced it had received up to $3.5 million in funding from CARB-X to develop its diagnostic technology, which uses a compact desktop device to detect the presence of bacteria in clinical urine specimens and to detect the antibiotics to which they are susceptible.

Lig Biowise, a UK firm developing point-of-care molecular diagnostics to help combat antimicrobial resistance, has raised £1.8 million ($2.5 million) in a Series A funding round. The company said it will use the funds to continue developing an "ultra-rapid" point-of-care diagnostic device and initial tests for respiratory tract diseases.

BARDA, a division of the US Department of Health and Human Services, recently awarded DNAe $10.98 million to develop an "alpha prototype" of its testing platform, and The National Institute of Allergy and Infectious Diseases has awarded Johns Hopkins University $4 million over five years to develop a microfluidic assay for sepsis that both identifies pathogens and performs single-cell phenotypic antimicrobial resistance testing. In June, Talis Biomedical announced it had been awarded a five-year grant for up to $5.6 million from the NIAID to support development of a point-of-care system.

Meantime, health systems have also upped their antibiotic stewardship initiatives. In a five-year study, clinicians at Children's Hospital Los Angeles demonstrated the ability of the Luminex Verigene gram-positive blood culture panel to effectively manage antimicrobial therapy by detecting the presence or absence of genes reflecting resistance to antibiotics.

And Williamson Medical Center in Franklin, Tennessee reported that it has reduced hospital stays, and in some cases avoided hospital admissions through using rapid molecular diagnostics as part of its antibiotic stewardship program.

On the industry side, some companies are betting their technologies in development will allow them to stand out in the antimicrobial resistance space.

SeLux Diagnostics is developing an antimicrobial susceptibility platform that it expects will deliver up to 50 AST tests per day, exceeding the workflow needs of labs and matching the throughput of the highest output systems currently in the market.

Also, First Light Biosciences is developing a molecule counting technology that detects Clostridium difficile toxin in stool samples with an eye on providing a more accurate testing option for clinicians struggling with the global growth of infections. Its MultiPath C. difficile toxin B test leverages digital imaging to count target-specific magnetic and fluorescent particles that have been tethered together by toxin molecules.

3i Diagnostics is developing a direct-from-blood testing platform that could eventually identify bloodstream microbes in about 20 minutes using infrared spectrometry and a new method of sample preparation.