Rapid antimicrobial susceptibility testing
Highly sensitive measurements of bacterial responses to single or combination testing of antibiotic efficacy – a new level of accuracy and speed in monitoring life and death
calScreener™ raw data
Heat over time curve
Integrated data, equivalent to bacterial growth curve
Escherichia coli planktonic growth in Mueller Hinton media. Normalized data vs control.
CalScreener measures the power produced from the sample in Joules per second or µW and gives a specific curve dependent on the specimen and the culture media. When CalScreener data is integrated over time the heat over time curve matches the conventional density growth curves from which the growth parameters can be calculated. Parameters such as maximum growth rate (the slope of the log phase in h-1) and the total biomass of the culture (Peak power in µW).
Antibiotic resistance is one of the greatest threats to humanity
Common human pathogens are becoming increasingly multiresistant. There is a pressing need for new antibiotics and faster diagnostic methods, in particularly novel methodology for testing multiple antibiotics in combination.
The classical AST methods such as broth microdilution (BMD) or disk diffusion have major limitations such us time and cost to results, but they also require large amounts of viable bacteria, analyses are restricted to a limited organism spectrum, sample processing is complex and results are based on subjective interpretation.
Symcel will change the management paradigm of AST by enabling customized solutions with rapid and accurate quantitative measurements. We bring solutions to this problem.
We measure life and death with precision
Direct metabolic readout – we measure the signature of life by monitoring metabolic changes of bacteria exposed to antibiotics, calScreener™ is the only solution that can do this and provide growth kinetics and long-term cell viability readouts
Define efficient combination treatments
A limited number of antimicrobials are available, and there is no commercial solution for combination therapy testing. We will set a new gold standard for combination testing
High sensitivity gives accurate data
The calScreener has a very high sensitivity and continuously monitors the metabolic response of bacteria exposed to antibiotics
Fast and real-time responses
Antibiotic susceptibility in less than 8 hours and the correct measurement of the cell kill- and inhibitory effects on bacteria means no false responses due to cell debris or lysed cells
Fast antimicrobial susceptibility determination
Early cutdown of the graph below
With calScreener early differences in growth can be detected, significantly reducing the time for AST and generating more reliable readout.
Currently, Symcel is clinically validating the calScreener to reduce the time for AST to 6 hours or less.
Escherichia coli planktonic growth in Mueller Hinton media, same experimental conditions as for BMD. Normalized data vs. control.
calScreener can be run as long as needed for the specific application and get a detailed metabolic behavior of the specimen.
In these graphs, the dose dependency of the antibiotic (AB) treatment can be objectively observed, and calculation of the minimum inhibitory concentration (MIC) with calScreener becomes a reliable and objective determination since it is not prone to false positive signals such as cell debris or metabolic inactive bacteria.
Versatile AST determination with any mono or combination antibiotic therapy
Klebsiella pneumoniae planktonic growth in Mueller Hinton media, same experimental conditions as for BMD.
Calscreener™ gives completely flexibility regarding the single or combo treatment, making AST most flexible and relevant.
In these graphs, it can be observed the lack of effect in the metabolism of the culture of the single antibiotic used. However, there is a clear additive effect when using the combination of antibiotics in the bacterial metabolism. Prolonged observation of the activity makes it possible to study re-growth, biofilm formation and late-stage survival of population subsets.
The bacterial species and strain give rise to unique metabolic thermograms
Bacterial planktonic growth in Mueller Hinton media, same experimental conditions as for BMD.
The unique heat flow footprint obtained in calScreener is dependent on the metabolism of the specimen, and this depends on the strain studied, as well as on the culture media and the availability of nutrients within it. calScreener can be employed for both gram-negative and gram-positive bacteria with equal sensitivity.
Multi-center clinical validation
Symcel aims to establish calScreener™ as a new diagnostic device for antibiotic susceptibility testing with key opinion leader labs around Europe during 2018-2020.
Symcel has received one of the largest Horizon 2020 grants ever awarded to a Swedish company, €3.6 million for three clinical studies in 5 different European labs. Read more about this exciting development here and please reach out if you are interested in discovering more.
Ass. Prof. Christian Giske
Chief Physician, Clinical Microbiology Department at Karolinska Hospital
Chairman, European committee on antimicrobial susceptibility testing (EUCAST)
“calScreener can be the solution to urgently needed customized treatments”
“Antimicrobial resistance is increasing rapidly and can cause infections that are extremely difficult to treat. Sometimes not even a single antimicrobial has remaining activity against these pathogens. The only possible management is customized solutions with rapid and accurate quantitative measurements. Moreover, there is a great need for testing several antimicrobials simultaneously, to predict the effects of combination therapy. Thus far there is no existing commercial solution for this problem which could be feasible to use in clinical laboratories.
The calScreener is uniquely positioned to potentially solve these problems and this is what enthused us to start testing Symcel’s technology in our research lab.”
Dr. Anni-Maria Örmälä-Odegrip
Senior Postdoc and Scientific Study Leader, Clinical Microbiology Department at Karolinska Hospital
“In antimicrobial susceptibility testing we have been able to significantly cut down the time”
“The calScreener is a unique device for monitoring bacterial growth – or inhibition of growth by antimicrobials. The most valuable attribute with the technique is that by monitoring the heat released in the system, it allows you to observe the bacterial metabolism in real-time, as opposed to optical methods, where the bacterial debris or metabolically inactive cells will give a signal – often resulting in a lag in the data.
In antimicrobial susceptibility testing we have been able to significantly cut down the time that it takes to observe if a given antimicrobial inhibits the growth of the bacteria. In bacterial growth measurements for analyzing the bacterial fitness, the unique metabolic patterns of individual species or isolates give us much more resolution on the analysis, and sometimes we have been a bit puzzled by being able to see phenomena that we would not track with other methods. But this is definitely a positive problem!
Our next step is to start routinely using calScreener for the screening process of selecting suitable bacteriophages for phage therapy for multidrug-resistant bacteria. The characteristics of the device are perfect for observing the detailed dynamics between the bacterial hosts and their viral parasites, giving us valuable information on which phages should be selected for further trials in the development process.”
Antibiotic-resistant bacteria are a growing concern, and with good reason—an estimated 23,000 deaths and two million illnesses occur annually in the U.S.1 Major contributing factors are overuse, lack of regulation and scarcity of novel antibiotics.
Antimicrobial susceptibility testing of microorganisms is performed by either disc diffusion or broth dilution tests. In clinical use, the tests are often still performed manually although automated systems exist. Most systems, however, are based on turbidometric methods which have well-known drawbacks.
In this study we evaluated isothermal micro calorimetry (IMC) for the determination of minimal inhibitory concentrations (MICs) of 12 antibiotics for five micro-organisms. Here we present the data for the 12 antibiotics and two representative microorganisms E. coli (a Gram-) and S. aureus (a Gram+). IMC was able to determine the MICs correctly according to CLSI values. Since MICs require 24 hours, time was not reduced. However, IMC provided new additional data – a continuous record of heat-producing bacterial activity (e.g. growth) in calorimetry ampoules at subinhibitory antibiotic concentrations. Key features of the heatflow (P) and aggregate heat (Q) vs. time curves were identified (t delay and Delta Q/Delta t respectively). Antibiotics with similar modes of action proved to have similar effects on t delay and/or Delta Q/Delta t.
IMC can be a powerful tool for determining the effects of antibiotics on microorganisms in vitro. It easily provides accurate MICs – plus a potential means for analyzing and comparing the modes of action of antibiotics at subinhibitory concentrations. Also IMC is completely passive, so after evaluation, ampoule contents (media, bacteria, etc.) can be analyzed by any other method desired.
Mycobacterium tuberculosis is a global public health concern, particularly with the emergence of drug-resistant strains. Immediate identification of drug-resistant strains is crucial to administering appropriate treatment before the bacteria are allowed to spread. However, developing countries, which are most affected by drug resistance, are struggling to combat the disease without the facilities or funds for expensive diagnostics. Recent studies have emphasized the suitability of isothermal microcalorimetry (IMC) for the rapid detection of mycobacteria. In this study, we investigate its suitability for rapid and reliable M. tuberculosis drug susceptibility testing. Specifically, IMC was used to determine the MICs of three drugs, namely, isoniazid, ethambutol, and moxifloxacin, against three mycobacteria, namely, Mycobacterium smegmatis, Mycobacterium avium, and Mycobacterium tuberculosis. The Richards growth model was used to calculate growth parameters, namely, the maximum bacterial growth rate and the lag phase duration from integrated heat flow-versus-time results. For example, MICs of isoniazid, ethambutol, and moxifloxacin were determined to be 1.00, 8.00, and 0.25 μg/ml, respectively. IMC, as described here, could be used not just in industrialized countries but also in developing countries because inexpensive and sensitive microcalorimeters are now available.