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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - BADGER (CalScreenerÂ® â€“ an innovative device for Bacterial Analysis and Diagnostics through Growth and Energy-release in Real-time)

Teaser

Summary

Symcel AB is a Swedish biotechnology company that provides a novel cell-based assay tool for real-time cellular bioenergetics measurements.

Through the BADGER project we intend to validate and commercialize our key product, the calScreenerTM, as an in vitro diagnostic tool. It is our primary goal to enter the diagnostic segment, specifically the areas where the need is greatest and unmet for efficient Antimicrobial Susceptibility Testing (AST) of multidrug resistant (MDR) sepsis causing bacteria.

In the EU antimicrobial-resistance has become a key public health concern and a central priority of EU health policy. Today, an estimated number of 25,000 patients in the EU die annually due to infections caused by resistant bacteria, a number projected to increase 10-fold to the year 2050.
In severe MDR bloodstream infections, the rapid increase in mortality for every hour left untreated together with a complicated antibiotics resistance profile, makes the tailoring of the right treatment very complicated.

Lack of a rapid, low-cost and readily available solution contributes to the inappropriate prescribing and overuse of antibiotics. Clinicians are in need of an accurate and rapid diagnostic test to increase antibiotic stewardship, introduce combination treatment for critically ill patients and help combat antimicrobial resistance (AMR).
As a result, tackling antimicrobial-resistance by developing innovative diagnostic tests and prescribing correct combination treatment have become a high priority worldwide.

The BADGER project is designed to address this exact problem.
The testing of combinations of antibiotics and identification of synergistic effects are the key objectives of BADGER. The ability to accurately determine the desired treatment combinations will lead to better cures and aid in the struggle against antibiotic resistance spread.

The potential solution to those unmet diagnostic needs lies in calorimetry-based clinical diagnostics. Calorimetry monitors the heat flow over time (J/s, W) enabling measurements of phenotypic response and growth dynamics to external factors such as antimicrobials. The BADGER project will validate a diagnostic device for the early, correct and timely diagnosis of MDR resistant bacterial infections. As such, we will play a significant role in addressing three of the five key objectives of the Global Action Plan on antimicrobial resistance presented by the WHO: strengthening surveillance, reducing the incidence of infection and optimizing the use of antimicrobial medicines.

In all, the BADGER project lay the foundation to clinically validate the calScreenerTM which will improve diagnostic decisions, provide a higher service level for patients, combat AMR and allow for more personalized and cost-efficient approaches to healthcare.

Work performed

With the overall aim of establishing calScreener as the gold standard for combination testing of antibiotics, for which no standard method exists today, the project is conducted in three clinical studies. The clinical evaluations are conducted at four major European hospitals in Sweden, Spain, Italy and the Netherlands, on four common sepsis causing pathogens; Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Acinetobacter baumannii.

Clinical study 1, aimed at validating calScreener susceptibility results (MIC) as being in concordance with the international ISO-standard for singular antibiotics testing (Broth microdilution; BMD) and to establish the timeframe to result, has been successfully completed.
A total of 159 isolates (40 isolates / species) with known antimicrobial susceptibility was tested against 10 of the commonly used antibiotics.
Results were in concordance with BMD, i.e validating the accuracy of the calScreener method, and gave significantly faster result, half that of BMD, thus validating the shorter time to diagnosis and treatment of patients.

Clinical Study 2, which is close to completion, focus on conducting susceptibility testing of extensively drug-resistant bacilli, using a combination therapy of antibiotics (synergy testing) as well as single agents. To evaluate and validate the effect of antibiotic treatment, results are also being compared with a sepsis animal model in case of synergy/combination testing. In this study, 158 isolates equally distributed between the sites was tested for single treatment and 107 isolates for combination therapy. The results thus far are very encouraging, validating the accuracy and precision of the calScreenerTM method in determining additive, synergistic as well as antagonistic effects of combinations of antibiotics.

To our knowledge, this is the first large scale study conducted applying IMC to antimicrobial susceptibility testing in a clinical setting. Moreover, the continuous recording of metabolic activity during antibiotic exposure provides a unique tool to study antibiotic phenotypic resistance.

Final results

By validating and commercializing calScreenerTM as a diagnostic tool, the BADGER project will make an important contribution to fighting AMR in Europe and increase the level of Antibiotic Stewardship. Moreover, we will improve the diagnosis and treatment of sepsis and importantly bring the first method to the market enabling combination testing of multiple antimicrobials simultaneously.

To this date no commercial method for combination testing exist, clinicians rely on empirical trial and error, on patients where every our left untreated rapidly increase mortality.

Current State-of-the-art for SINGLE antimicrobial testing
The gold standard, BMD, is accurate but very slow (16-20 h). The surrogate disc diffusion method may provide results within 6 h, however has shown a poor correlation with BMD and very difficult to use for MDR bacilli. Results are qualitative, and do not provide the important quantitative MIC-value. Both methods are labor intensive and low through-put and only allow limited possibilities for testing.

New state of the art â€“ enabling combination testing
The novelty of the proposed calScreenerTM diagnostic device lies in its unmatched sensitivity and specificity, directly and label-free measuring the metabolic activity (simply described as alive or dead). This providing the clinically relevant guidance for correct antibiotic treatment, in particular for combination therapy.

The calScreenerTM can be used on any sample format, whether liquid or solid and no reagents at all are needed, greatly reducing the time to results and cost.

In all, the economic benefits of the calScreenerTM derive from the unprecedented opportunities to radically decrease costs related to diagnosis and treatment of severe bacterial infections.
Indirectly, the use of calScreenerTM will lead to a reduced use of antibiotics and consequently to reduced socio-economics costs of antimicrobial resistance. The societal benefits include a) shorter time to diagnosis and treatment, b) personalized approach to treating infections c) improved clinical outcomes d) significant role in combating the significant healthcare issue of AMR.

In thanks to the BADGER project we expect to take the calScreenerTM instrumentation closer to the clinical diagnostics market and IVDR CE-marking, with special emphasis on synergy testing and combination therapy.