Day Zero sees positive data with tech to diagnose superbug infections

By Liz Hollis, Staff Writer

Day Zero Diagnostics Inc. has reported that data presented at IDWeek highlighted the promise of the company’s new class of diagnostics as it works toward its goal of detecting superbug infections quickly. The company ultimately is hoping to get regulatory signoffs in both the U.S. and Europe for its technology.

Boston-based Day Zero is developing a diagnostic system that aims to help patients with severe infections receive the most effective antibiotic treatment on the first day they are admitted to the hospital.

It is designed to enrich and extract bacterial DNA directly from a patient sample for sequencing, without the need for a time-consuming culture. It also has developed a machine-learning algorithm that analyzes the genomic data to identify the pathogen and determine its antibiotic susceptibility and resistance profile within hours.

Against that backdrop, researchers revealed interim results from the Boston Medical Center Rapid Bacterial Identification Trial that showed that Day Zero’s culture-free assay for determining the presence of a bacterial infection and its species were concordant with clinical blood cultures in 96% of samples. In addition, the results indicated that Day Zero’s assay is potentially more sensitive than culture-based diagnostics.

Also of note, Day Zero has had no false-positive results to date.

Nina Lin, assistant professor at Boston University School of Medicine and director of the Boston University Infectious Disease Clinical Research Unit, presented the results and acknowledged that they were early. With that said, they pointed to the promise of identifying bacterial pathogens without a culture. “Current culture-based diagnostics have slow turnaround times and low sensitivity,” she noted, adding that clinicians have been forced to rely on broad-spectrum antibiotics. Doing so has produced poor outcomes and contributed to the rise of antibiotic resistance.

“This new approach is promising because it provides clinicians with rapid and precise information that is essential for treating patients with targeted therapies,” Lin emphasized.

Validation study

IDWeek also featured the presentation of results from a separate validation study of Blood2Bac, which was assessed in its ability to recover the whole genomes of pathogens. It was tested across 50 bacterial species spiked into whole blood at concentrations as low as 1 colony- forming unit per milliliter/mL.

Results demonstrated that Blood2Bac, when paired with Keynome, was able to achieve an average of 95% whole-genome coverage and correctly identify all 50 species with 100% accuracy even at single-digit bacterial concentrations.

“We’ve spent the last few years developing the core technologies necessary to make bacterial whole genome sequencing directly from blood feasible for clinical decision-making,” Jong Lee,

Day Zero’s CEO, told BioWorld. “We are extremely proud of that work, and the validation work we have done to have confidence in those capabilities, the results of which are starting to be shared at IDWeek.”

The company hopes to integrate these capabilities into an in vitro diagnostics (IVD) that may be brought into hospital microbiology labs.

Lee noted when asked if others were adopting a similar approach that there are a host of companies looking to develop next-gen diagnostics for sepsis. Most of them, however, use culture as the sample. “[S]o, they are gated by the time required to grow the culture and are unusable when culture doesn’t grow,” he explained. “There are a handful of molecular diagnostics that work directly from blood at the sensitivity required to be clinically relevant, but all of them are limited to the identification of a handful of species. It’s impossible to profile AST (Aspartate Aminotransferase) comprehensively using biomarker approaches.”

There are other players in the infectious disease diagnostic space that use sequencing, but they have send-out services that can require a lot of time to culture “and work with fractions of the genomic data that have led to a high rate of false positives and make comprehensive AST determination impossible.”

Lee’s company has devoted itself to developing a locally executable whole-genome sequencing diagnostic that works directly from blood at the levels of sensitivity necessary for clinical decision-making.

“Because we have developed a technology that is capable of recovering the full genomic sequence rather than just fractional parts of the genome, we are able to use it to make highly reliable species ID determinations as well as to comprehensively profile AST.”

His organization already offers certain services to hospitals. Its epixact® service for hospital- acquired infection determination is an example. “We are exploring making other elements of our technology available for clinical use in the near future, but a fully integrated IVD will take time to design, build and test and so it may be a few years before that system is available,” he added.

Looking ahead, the company intends to strike up collaborations to have leading institutions test its diagnostic approach in clinical trials. That is intended to lead to potential discussions with the physician community about how the company’s diagnostic could have an impact on clinical decision-making.

“In addition, we anticipate doing some innovative pilots with leading academic medical centers on the use of sequencing to provide a big data view of the flow of pathogens through the microbiology lab. These pilots are designed to start articulating a vision for the future of hospital microbiology that we think will be transformative,” Lee said.