Project Case | Health & Agrofood |Fastinov, S.A.
The pace of diagnostic processes in clinical microbiology laboratories has largely been unchanged for almost 100 years, as availability of diagnostic results essentially depended on the growth of bacteria. Using traditional approaches, it takes at least 24 hours for obtaining growth from clinical specimens, and an additional 24 hours for downstream isolate characterization (i.e. biochemical identification and phenotypic susceptibility testing). As a consequence, therapeutic decisions are commonly made empirically until the availability of species identification and resistance patterns.
Furthermore, the emergence of pathogens carrying acquired resistance determinants, e.g. methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase- (ESBL-) producing Enterobacteriaceae, or carbapenem-resistant Gramnegative rods, has resulted in increasingly broad empiric treatment regimens, often including glycopeptides and broad-spectrum betalactams such as piperacillin-tazobactam or carbapenems. The
resulting overuse of these reserved agents itself drives the emergence and spread of multi-resistant organisms.
The situation is aggravated by the often unsuccessful recovery of pathogens from patients receiving prior broad-spectrum antibiotics and, in consequence, unavailability of subsequent drug susceptibility data. Moreover, it is a common problem that (successful) empiric broad-spectrum therapy remains in place although microbiological test results justify de-escalation. Therefore, it is evident that overtreatment is, at least partially, linked to the discrepancy between traditional microbiological procedures and the clinical need for more rapid results.
Early availability of information on bacterial pathogens and their antimicrobial susceptibility is of key importance for the management of infectious diseases in humans and animals. Moreover, current global emergence and spread of antimicrobial resistance is a major medical/veterinary and economic problem.
When an infection is diagnosed, the physician/veterinary is required to start an empiric large spectrum therapy, since current comprehensive and proven susceptibility profile methods require, at least, 48h. Therefore, the slowness of diagnostic procedures drives prolongation of empiric, potentially inappropriate, antibacterial therapies.
Over the last couple of years, the improvement of available techniques (e.g. for susceptibility testing, DNA amplification assays), and introduction of novel technologies (e.g. MALDI-TOF) has fundamentally changed approaches towards pathogen identification and characterization. Importantly, these techniques offer increased
diagnostic resolution while at the same time shorten the time-toresult, and are thus of obvious importance for antimicrobial stewardship.
Accelerated phenotypic methods, molecular techniques, MALDI-ToF and next generation sequencing (NGS), all hold promise or have already proven to not only optimize workflows within the lab, but also to offer increased diagnostic resolution and decreased time-toresult.
In recent years it’s been implemented a common policy in the EU, an action plan against Anti-Microbial Resistance (AMR). Its overarching goal is to preserve the possibility of effective treatment of infections both in humans and animals, since the increasing emergence of resistance to antibiotics has led to less effective treatment of common bacterial infections.
AMR increases as a consequence of multiple mechanisms of resistance in expanding bacterial populations and selection pressure from antibiotic use, which provides a competitive advantage for those strains. Due to current antimicrobial susceptibility testing (AST) methods have a turnaround time of at least 24 hours, delayed
and inadequate treatment decisions are taken. Therefore, there is an urgent need for a fast and accurate AST method.
This is the opportunity context of this project, Fast-vet: Flow cytometry Antimicrobial Susceptibility Test for Veterinary, an innovative method for AST promising a revolution on veterinary microbiology. These novel AST tests will employ flow cytometry and yield accurate determination of the susceptibility phenotype within 2 hours, compared with the more than 48 hours needed for current standard methods. These changes can be measured well before effects on bacterial growth (i.e. the read-out of current methods) become apparent. Furthermore, these specific changes can be measured using different fluorescent probes, enabling clinicians to begin optimal antibiotic treatment sooner, with a major impact on health and quality of life of patients impacting on health costs.
Using this method, AST can be performed either directly on a positive blood culture or on bacterial cultures. These tests have already a TRL of 7 or 8 in the Health field, and its applications to Veterinary and Agrofood are very new, making so a real cross-sector transference of know-how. Impact of innovation is clear since early detection of resistance to antimicrobials would potentially save a lot of animals, avoiding the use of antimicrobial drugs, with evident economic, environmental and even human health impacts.
In this sense, by providing a fast susceptibility profile and guidance support for clinical prescriptions and decisions in acute care settings, project strongly contributes to the reduction of medication costs, clinical therapeutical failure, diagnostic and treatment costs, antimicrobial resistance and spread of multi-resistant strains.
The company, FASTinov, is a spin-off from the Faculty of Medicine, University of Porto, a R&D intensive start-up with a patented disruptive technology to perform fast and reliable antimicrobial susceptibility tests in acute care settings. It has already developed two novel prototypes for rapid and accurate AST of both Gram-positive and Gram-negative bacteria.
FASTinov S.A. has a multidisciplinary team with scientific expertise in microbiology and dedicated flow cytometry techniques, combined with the extensive knowledge of current needs in the field of infectious diseases. The team was created by 3 Microbiology Professors and it is now composed by 5 full time workers (3 PhD and 2 masters). Additional two consultants, expert in translation of the technology to the market, belong more recently to the team.
Participation in ACTTiVAte has facilitated integration into a consortium network that will allow the scale-up of the company, as well as completion of a prototype validated with first users. Next future looks like optimistic for the project. Its patented methodology (Flow Cytometry Antimicrobial Susceptibility Test- Fast) fills a gap in existing AST methods: microbial cells can now be discriminated in terms of Susceptible vs Resistant phenotypes, independently of growth, filling the opportunity need of susceptibility profile in clinically useful time.