Bruker today announces an exclusive licensing agreement with Erasmus Medical Center, Rotterdam, The Netherlands for rapid testing of beta-lactamase activity using MALDI-TOF technology. This new method is fully compatible with the well-established Bruker MALDI Biotyper system, which is used for MALDI-TOF mass spectrometry-based identification of microorganisms in over 700 clinical and non-clinical microbiology laboratories worldwide.
In many laboratories, the MALDI Biotyper has replaced classical biochemical testing for bacterial identification in the past five years due to the accuracy, speed, extensive species coverage, ease of use and cost effectiveness of the system. Classical biochemical techniques depend upon detecting different metabolic properties of microorganisms; however, these techniques can take hours or even days for completion and they lack specificity. The MALDI Biotyper uses a molecular approach based on specific proteomic fingerprints from bacterial and fungal strains and published studies have highlighted the greater accuracy offered, as well as the typically much faster time-to-result (TTR). With an installed base of more than 700 MALDI Biotyper systems at the end of 2012, Bruker estimates that in the year 2012 its customers performed about 20 million microbial identifications on the MALDI Biotyper installed base.
In addition to this paradigm shift for microbial identification, the MALDI Biotyper is increasingly being used for functional resistance mechanism detection. Antibiotic resistance is an ever increasing problem as bacteria acquire new mechanisms of resistance against classes of antibiotics currently being used in clinical care. Data from the WHO European Region shows that resistance of some pathogens now reaches over 50% in some countries, and new resistance mechanisms are emerging and spreading rapidly. In the European Union, Norway and Iceland it is estimated that 400,000 resistant infections are occurring every year, leading to approximately 25,000 deaths.
Gram-negative bacteria are a common source of infections and pose significant challenges due to their ability to rapidly acquire new resistance mechanisms resulting in multi-drug resistant (MDR) strains. One such mechanism of resistance found in gram-negatives is Extended Spectrum Beta-Lactamase (ESBL) in which enzymes produced by bacteria attack and cleave the beta-lactam ring in antibiotics, thus rendering them ineffective. This includes penicillins, and third generation cephalosporins. Another mechanism is resistance to Carbapenems, which frequently are the drugs of last resort for clinicians when other antibiotics have been ineffective due to resistance.
Consumption of carbapenems increased significantly in European countries from 2007-2010 and occurrence of carbapenem-resistant Klebsiella pneumonia is already high and increasing in some European countries. Recent publications in both the scientific and popular press have high-lighted the challenge and outbreaks associated with microorganisms containing ESBL mechanisms including reports on NDM-1, KPC and most recently CRE (Carbapenem-Resistant Enterobacteriaceae). Accurate and rapid detection of resistance is essential for effective infection control measures, as current techniques lack either specificity or rapid turn-around time.
MALDI-TOF mass spectrometry allows for an exact determination of the molecular weight of a broad range of antibiotics. In the presence of an ESBL, the antibiotic is converted to fragments of predictable molecular weight which are also measured using the MALDI Biotyper. As with bacterial identification, the MALDI Biotyper is thus anticipated to provide both improved, shorter time-to-result as well as potentially better specificity.
Dr. Theo Luider, Head of the Laboratories of Neuro-Oncology, Department of Neurology, Erasmus University of Rotterdam, pointed out: "We have been working with MALDI-TOF mass spectrometry for many years originally in the field of clinical proteomics, but more recently the increased usage of the MALDI-TOF approach for microbial identification also became an area of interest for us. We have filed a PCT patent for the characterization of beta-lactamase activity by MALDI-TOF mass spectrometry with the title "Methods and means for characterizing antibiotic resistance in microorganisms". With their outstanding expertise in mass spectrometry and clinical microbiology market presence, we think that Bruker is the right partner to bring such novel assays to the market."
Dr. Stefan Zimmermann, Department of Infectious Disease, Medical Microbiology and Hygiene,at the University Hospital Heidelberg, commented: "We have been using MALDI Biotyper-based functional beta-lactamase assays in our hospital for roughly two years with the main application being epidemiology and hospital hygiene. It is of great importance to know as early as possible, especially in the intensive care unit, if a new patient carries a carbapenem-resistant Klebsiella pneumonia (KPC). In this case we are able to isolate the patient sooner than with older phenotypic methods. MALDI Biotyper-based KPC-testing improves patient health and at the same time improves cost-efficiency of the Intensive Care Unit by limiting the isolation of patients to those cases where it is really necessary."
Dr. Wolfgang Pusch, Executive Vice President - Microbiology Business at Bruker Daltonics, added: "The signing of this exclusive license agreement with the Erasmus Medical Center is another major milestone in our MALDI Biotyper strategy. While MALDI Biotyper-based microbial identification is already established in many countries, we see significant growth potential in MALDI-based beta-lactamase testing. The exclusively licenced IP from Erasmus Medical Center further strengthens our own broad portfolio of intellectual property in the field of mass spectrometry-based microbial analysis ranging from sample preparation, data processing, MALDI-TOF technology, direct analysis from positive blood cultures and beta-lactamase testing, and offers laboratories worldwide another tool in the fight against resistant bacteria."