Molsid achieves the first rapid phenotypic diagnostic test for AMR on primary clinical samples. Pre-clinical trials on urinary tract infections (UTI) show that all beta-lactamase and carbapenemase enzyme activities can be detected in resistant E.coli strains
Since their discovery, antibiotics have helped eradicate several infection-based diseases that had inflicted untold suffering on humanity. Today, the efficacy of antibiotics is jeopardized by the emergence of bacterial resistance to antibiotics. Health agencies like the World Health Organization (WHO) now frequently alert the public to the discovery of a growing number of resistant strains at the origin of major diseases. Of major concern are the strains that even resist the latest antibiotics.
These recent antibiotics serve as “last resort” solution against bacterial infections when pathogens are resistant to other more ancient or more commonly used antibiotics. Risks linked to the administration of these last resort antibiotics are high first because “last line” antibiotics could become uncurable (with no alternative treatment as to today) and second because their side effects are often difficult to cope with for the patient. Last resort antibiotics are mostly administered when multi-drug resistant pathogenic bacteria cause illness or nosocomial outbreaks (when acquired in a hospital). These multi-drug resistant pathogenic bacteria have been regrouped in an acronym and are considered as the most dangerous by the WHO:
ESKAPE or ESKAPEE:
E = Enterococcus faecium (Link: https://en.wikipedia.org/wiki/Enterococcus_faecium )
S = Staphylococcus aureus (Link: https://en.wikipedia.org/wiki/Staphylococcus_aureus )
K = Klebsiella pneumoniae (Link: https://en.wikipedia.org/wiki/Klebsiella_pneumoniae )
A = Acinetobacter baumannii Link: https://en.wikipedia.org/wiki/Acinetobacter_baumannii )
P = Pseudomonas aeruginosa (Link: https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa )
E = Enterobacter spp (Link: https://en.wikipedia.org/wiki/Enterobacter )
Most often complemented by
E= Escherichia coli (https://en.wikipedia.org/wiki/Escherichia_coli )
More information on ESKAPE/E here:
Globally, antimicrobial resistance is a major and growing public health issue. If nothing is done, more than 10 million people will die each year from AMR by 2050 (source: WHO).
AMR is especially a concern in the hospital environment. It is responsible for nosocomial outbreaks, longer hospital stays and therefore increased healthcare costs and the deterioration of prognostic outlook for patients, especially in intensive-care units where time matters.
Early detection of antimicrobial resistance is key to improved therapeutic treatment of patients infected by certain pathogenic bacteria such as nosocomial agents, known to present multiple resistances to antibiotics. A serious problem in an epidemic context is a propagation due to delayed identification of patients harbouring resistant strains.
Antimicrobial susceptibility testing (AST)
Many rapid diagnostic techniques allow for pathogen identification and some of them can also detect the presence of resistance-related genes or proteins. However, most AST products require the initial clinical sample to be processed by bacterial culture. This significantly slows the workflow until a decision can be made which antibiotic is well suited for treatment.
Today modern AST techniques include technologies based on nucleic acid amplification (PCR), whole genome sequencing, and hybridization as well as immunodiagnostic and mass spectrometry-based methods and biosensor-based AST.
Each method has various benefits and limitations, especially in terms of time-to-decision, sample preparation and precision.
Molsid’s PYTHIA is the first phenotypic test combining the following benefits:
The graphic shows typical results obtained using our dedicated fluorescence reader (link). Centrifugation allows to concentrate the fluorescent signal generated by the entire clinical sample in the form of a fluorescent pellet. This ensures PYTHIA’s exceptional detection sensitivity. It further permits the quantitation of bacterial count with a threshold of only one thousand bacteria per milliliter of urine, an unprecedented value for primary clinical samples, and this at an astonishingly short incubation time (1 hour).
We are proud to call the following institutions our partners and/or supporters in the development of PYTHIA:
Our molecular probes detect enzyme activity produced by microorganisms. Molsid’s PYTHIA test allows for the phenotypic detection of bacterial resistance to beta-lactams and carbapenems in around 2 hours as opposed to 48 hours with conventional methods.
This probe is designed to detect bacteria that produce beta-lactamase activity, a class of enzymes responsible for the resistance to beta-lactams, a broad class of antibiotics. Beta-lactams comprise penicillins, cephalosporins, monobactams, carbapenems and beta-lactamase inhibitors. They are the reference treatment for pneumococcal infections.
This probe is designed to detect bacteria that produce carbapenemase activity. Carbapenemases are responsible for the resistance to carbapenems. This resistance occurs mainly in Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, as well as in Enterobacteriaceae.
Contrary to conventional fluorogenic enzyme-responsive probes, Molsid’s SmartID probes generate localized fluorescence, i.e. fluorescence that does not diffuse away from the site of the targeted enzyme activity. This allows for precise, unambiguous discrimination of positive from negative cells.
β-lactam-resistant and sensitive bacterial cultures revealed by SmartID probe (under UV lamp)
Detection of β-lactam-resistant bacteria by SmartID probe directly on agar plate (under UV lamp)
Molsid’s product pipeline includes rapid AMR Diagnostic (Dx) kits for the detection of
staphylococci and for Urinary Tract Infections, in a first place. Other kits will follow such as kits
adapted to other sample types (saliva, CSF, swab, etc.) and certain bacteria strains. We will
widen our portfolio within two years to fast antibiograms (detection in 3 hours compared to usually
12) and AMR Diagnostic (Dx) kits for the veterinary use.
Screening of different clinical bacteria isolates with SmartID probe on a 96-well plate.
β-lactam-resistant bacteria and β-lactam-sensitive bacteria appear green (resistant) and blue
(sensitive) under UV lamp.