Project: Rapid Determination of Bacterial Drug Resistance by Automated Disk Diffusion
Bacterial infections are amongst the major causes of disease and death in man. Infection prevention, treatment and control are topics of worldwide interest. Infection control is complicated through disease-causing microbes that have become resistant to antimicrobial drugs. Tuberculosis, bloodstream infections, MRSA infection and ESBL infections are just a few examples of diseases that have become difficult to treat with antibiotics. Antimicrobial resistance is thus a growing threat to public health._x000D_ _x000D_ The development of antimicrobial resistance is enhanced by the use and misuse of antibiotics and the spread of already resistant bacteria. Empirical therapy, in which a cocktail of (i.e. a broad spectrum) antibiotics is applied, increasingly fails. Delays in effective treatment of systemic infections are accompanied with increased morbidity and mortality. _x000D_ _x000D_ The use of highly specific (small spectrum) antibiotics will prevent (or at least slow down) the development of more resistance. Therefore, the rapid detection, identification and susceptibility testing of bacteria is of utmost importance to control infections in modern medicine. Yet, it is common practice in microbiological laboratories to take two days to isolate and identify the bacterium and test it for susceptibility to antibiotics. Although recent developments of novel MALDI-TOF technology allow fast identification, development of breakthrough technology in antimicrobial susceptibility testing (AST) to determine the most effective antibiotic treatment method, has not been achieved. _x000D_ _x000D_ Currently, the method most often used in clinical laboratories in AST is by disk diffusion. This method uses antibiotic disks to test whether bacteria are susceptible to specific antibiotics. Culture plates are used to grow a known quantity of bacteria in the presence of these antibiotic disks. If the bacteria are susceptible to a particular antibiotic, a zone of clearing will surround the disks where bacteria were unable to grow. This zone is called the inhibition zone . The larger the zone, the higher the susceptibility. Disk diffusion is relatively cheap, but has long time to result (TTR) as the method is performed manually and standard AST protocols call for 16-20 hours of incubation before tests can be read. _x000D_ _x000D_ To reduce the TTR to approximately 8-12 hours, over the last decades several automated AST methods have been introduced on the market, such as Phoenix™, VITEK®and MicroScan®. These methods are based on automated reading of bacterial growth through measuring optical density , in which a pre-set range of antibiotics (6-8), fixed in so-called sensi cards, is tested. Downside of these methods is that they lack flexibility, are expensive and most often their capacity is limited. _x000D_ _x000D_ Moreover, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently published a list of clinical breakpoints and related expert rules based on a standardized disk diffusion test as European recommended AST method. Due to these EUCAST guidelines and the limitations of current automated AST methods, the interest in the traditional disk diffusion methods has been re-awakened. With this market pull, the growing need for a reliable (robust and objective) and rapid disk diffusion test is evident._x000D_ _x000D_ BD Kiestra (here after: Kiestra) and its project Ps recognize this market opportunity and anticipate to meet this medical need by the development of the innovative Rapid Disk method, which will allow:_x000D_ - A cost-effective automated AST method based on disk diffusion;_x000D_ - A shortened TTR by significantly reducing the reading time for the disk diffusion test from 16-20 hours to 6-8 hours through an intelligent and highly automated system;_x000D_ - A more robust and reliable AST method through a high level of standardization;_x000D_ - Increased flexibility to permit customized antibiotic testing (compared to fixed testing panels in current automated AST methods);_x000D_ - Smart automated pre-selection of antibiotic disks based on demographics, sample type, bacterial identification and clinical patient details to reduce costs and reading time and to improve the selection of the appropriate antibiotic treatment method;_x000D_ - Faster interpretation of AST results through integration of EUCAST databases and expert rules. _x000D_ _x000D_ The combination of these factors allows improved infection control and can contribute to the impediment of antimicrobial resistance thereby forming the desired breakthrough in medical microbiology. _x000D_ _x000D_ The developments in this Rapid Disk project will lead to a number of commercial products (analysis software, automated incubation hardware, innovative detection hardware and -software, etc.), providing the CO participant to move from automated bacterial identification systems into the new and fast growing market of (automated) bacterial susceptibility testing. Of course, the European project Ps also will significantly benefit from these developments. _x000D_
| Acronym | Rapid Disk (Reference Number: 6187) |
| Duration | 01/01/2011 - 31/12/2013 |
| Project Topic | This project aims to develop a fully automated, high throughput, intelligent antimicrobial susceptibility testing (AST) system, based on disk diffusion, that is able to pre-select antibiotics and allows early interpretation of AST results (6-8 hours) by using EUCAST expert rules. |
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Project Results (after finalisation) |
The CO achievement was, that we in three different laboratories could show, that susceptibility in different, but most frequent seen bacteria species, and both the natural occurred bacterial population, and the ones with acquired resistance mechanisms, could be read reliable after six hours. This was shown for numerous bacterial species, and both for huge collection of bacteria with well-defined susceptibility and various resistance mechanisms, and for consecutive clinical isolates. It was done on manually, and on semi-automatized Kiestra systems, beside with a special project camera (used for training for automatic zone reading). _x000D__x000D_We also were part in the development of an intelligent and automatic camera-reading of zones in the susceptibility testing, - as the most advances on the market today, has to adjusted manually for computer reading of zones, before transforming the zones to categorical values as susceptible (S), intermediate (I), and resistance (R ), used to guide clinicians in the choice of treatment. The camera used in the routine now, also invented by Kiestra, still has to be adjusted, and we have not yet seen the intelligent camara on the market. _x000D_ |
| Network | Eurostars |
| Call | Eurostars Cut-Off 5 |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 5 | BD Kiestra | Coordinator | Netherlands |
| 5 | Central Hospital Vaxjo (Clinical Microbiology) | Partner | Sweden |
| 5 | Copenhagen University Hospital, Hvidovre | Partner | Denmark |
| 5 | Oxoid Ltd. | Observer | United Kingdom |
| 5 | Radboud University Nijmegen Medical Centre | Partner | Netherlands |