Four Rapid AST Solutions Hit the Market over Six Months
Sepsis is one of the leading causes of death in hospitals, contributing to 49 million cases worldwide in 2017 (Rudd 2020). Timely diagnosis and treatment with appropriate antibiotics are crucial for patient survival. Until recently, laboratories had two solutions to improve turnaround times for obtaining antimicrobial susceptibility results for positive blood cultures: the Accelerate Pheno® system for ID and AST results, and direct disk diffusion using the updated CLSI breakpoints for positive blood cultures.
Over the past six months, four novel technologies for AST directly from blood culture have received FDA clearance: Affinity Biosensors’ LifeScaleTM AST, Biomerieux’s VITEK® REVEALTM, Q-Linea’s ASTarTM System and the Selux Diagnostics Selux PBC SeparatorTM with their AST system. Each test uses innovative methodologies to obtain MIC values in as little as four hours from bottle positivity.
The Need for Rapid AST Solutions
Numerous publications have highlighted the risks to septic patients when inappropriate treatment is given. Kumar et al. found a five-fold decrease in survival rates when initially given inappropriate antibiotics and saw a 7.6% increase in morality for every hour that treatment was ineffective (Kumar 2006). Despite the use of broad-spectrum empiric treatment, up to 20% of patients receive inappropriate initial therapy (Kumar 2009).
A recent cross-sectional study assessed the effectiveness of empiric treatment of sepsis patients based on pathogen resistance profiles (Ohnuma 2023). The authors found that empiric treatment covered 94.4% of susceptible gram-negative rods, 97.0% susceptible gram-positive cocci, and 65.1% of Candida species. However, coverage decreased to 55.3% when a carbapenemase was present or to 60.4% for vancomycin-resistant Enterococcus was causing the infection.
These data demonstrate a need for more rapid diagnostics for obtaining susceptibility results compared to the current traditional blood culture methods that can take 48+ hours to get results.
At a glance —
- Sepsis contributed to 49 million cases worldwide in 2017, highlighting the need for timely diagnosis and treatment.
- Rapid AST is crucial due to the high mortality risk associated with inappropriate initial antibiotic treatment.
- Prior to the latest advancements, rapid AST relied on two primary systems for blood cultures.
- Four new AST technologies have recently received FDA clearance, offering MIC results in as little as four hours.
- These new solutions use innovative methodologies, marking significant progress in clinical microbiology and sepsis management.
First Options Direct from Positive Blood Cultures
In 2017, Accelerate Diagnostics received marketing authorization for the Accelerate Pheno system through de-novo reclassification. The system performs ID and reports MIC values directly from positive blood cultures. It combines fluorescent in situ hybridization, microscopy, and image analysis to measure replication of bacterial cells in the presence and absence of antibiotics. The assay delivers results within 7-8 hours and identifies the most common pathogens causing bloodstream infections.
Shortly thereafter, rapid disk diffusion became an option that laboratories could adopt using the updated CLSI breakpoints for positive blood cultures. This testing is cost effective, but labor-intensive. Positive blood cultures are spread onto Mueller Hinto Agar, antibiotic disks are placed, and preliminary results are available within 8 hours. This workflow takes advantage of obtaining results prior to isolation and growth of bacterial colonies for testing. However, the method is limited if the culture is mixed. Advancements in laboratory automation from companies like Copan and BD could streamline this workflow by automating plating, disk placement, and reading of these plates.
Four Novel Solutions in Six Months
In February 2024, Selux Diagnostics announced receiving FDA clearance for the Selux PBC Separator with the Selux AST System. The multi-instrument system processes positive blood cultures and inoculates panels with up to 384 wells. Each well is evaluated to report a MIC value. Reporting is based on what the company defines as next-generation phenotyping, which measures metabolic viability and morphological surface area changes. Processing takes about 1 hour for up to 2 specimens, with results available in 5-6 hours after panel incubation.
The LifeScale AST received FDA clearance in April 2024. It evaluates MIC by inoculating a standard number of bacterial cells into a 96-well broth microdilution plate. The system then measures the bacterial cells in each well over time creating a population profile based on cell mass. Software then interprets these profiles with and without antibiotics to generate a MIC within 4.5 hours. The test is FDA cleared for a gram-negative panel and needs to pair with a rapid ID method such as MALDI-ToF MS or molecular to perform the interpretation of the results.
Later that same month, April 2024, Q-Linea received FDA clearance for its ASTar System, a fully automated system that processes the positive blood specimen and standardizes inoculation into its multichannel disk. Various antibiotic concentrations are added to each channel and time-lapsed microscopy imaging is used to determine MIC results. Results are reported in approximately 6 hours for bottles containing gram-negative organisms.
In June, bioMérieux announced receiving FDA clearance for its AST System VITEK REVEAL. The VITEK REVEAL also uses a 96-well microbroth dilution approach, but uniquely detects volatile compounds released during bacterial growth (think grape smell from P. aeruginosa). Their proprietary cover detects various compounds released and reports an MIC value within about 5.5 hours. This assay also requires a separate ID method to perform interpretation of AST results.
Remarkable Timing Given the Complexity
In our experience, it is exceptionally unusual for four new automated antimicrobial susceptibility testing (AST) solutions to enter the market within such a short period. The variability in microbial resistance patterns across different regions and populations necessitates complex studies to evaluate multiple drug/bug combinations along a range of MIC values with various resistance patterns. The clearance of these new solutions in such a short timeframe is a notable achievement and demonstrates the commitment of the FDA, industry, and clinical partners to generate safe and reliable solutions to improve patient care.
This new wave of technology for rapid AST directly from positive blood cultures is an exciting frontier in clinical microbiology and has promising implications for sepsis management. However, real-world evidence is needed to demonstrate their clinical utility. Lessons learned from rapid molecular testing suggest potential benefits such as decreased time to effective therapy and hospital stay, although the use of an antimicrobial stewardship program is crucial for maximizing these benefits and reducing mortality rates (Timbrook 2016). Those stewardship programs, now having more options to support targeted therapies based on MIC data, should be a step forward in combating sepsis.
Working on an AST project?
MDC Associates has years of AST-specific experience and the team has brought multiple AST devices successfully through clinical studies process to meet the requirements for FDA approval. Reach out to us if you’d like to discuss your project.
