When a symptomatic four-week-old boy recently landed in the emergency room at Montefiore Medical Center, it took less than 14 hours from the time his blood was collected to identify a Group B Streptococcus infection. The antimicrobial stewardship team was immediately notified of the laboratory results so that the team could assist the treating clinician in determining appropriate antimicrobial treatment.
The speedy turnaround time was a result of identification of the bacteria directly from the positive blood culture bottle using Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry, an innovative technology that offers a significant improvement over bacterial identification by conventional microbiological testing methods. Without the use of MALDI-TOF, identification of his life-threatening infection would have taken at least an additional 12 hours.
A more accurate approach
MALDI-TOF has been in use in Montefiore’s clinical microbiology laboratory since January of 2014. The analytical method of microbial identification and characterization is based on the fast and precise detection of the protein signature of an organism. Montefiore’s microbiology lab has been granted New York State approval to identify bacteria growing on culture plates and directly from blood cultures bottles, allowing for a faster turnaround.
“It’s a more accurate, molecular approach to identifying an organism within minutes,” said Dr. Michael Levi, director of Montefiore’s Microbiology Laboratory. “Early diagnosis and prompt identification of organisms in conjunction with early interventions by the antimicrobial stewardship team may help to limit a patients’ exposure to unnecessary antibiotics and reduce the risk of drug resistance," he said, "as well as improve patient care outcomes and decrease health care expenditures.”
Until recently, Montefiore relied on traditional organism identification methods, many of which rely on microbial utilization of biochemicals. While effective, these techniques are time-consuming. For example, traditional phenotypic testing of Escherichia coli – the most prevalent gram-negative bacteria in a hospital setting – often takes several hours after the growth of the organism on culture media.
“We are able to identify ~70% of bacteria directly from positive blood culture bottles,” said microbiology lab supervisor Wendy Szymczak, PhD. “When successful, we get the identification to the clinician 8 to 12 hours earlier than if we had to wait for the subcultured organism to grow on the culture plate,” added Dr. Szymczak, who has helped to implement and track the effectiveness of the MALDI-TOF technology.
When it comes to bloodstream infections - particularly gram-negative bacteria - time is the enemy. “The more rapidly you know what you’re treating, the more directed you can make the therapy and the better the outcome,” said Dr. Louis Weiss, an Infectious Disease specialist at Montefiore and Professor in the Departments of Pathology and Medicine at Einstein.
MALDI-TOF can be used to identify bacteria directly from positive blood culture bottles after extracting bacterial proteins. Alternatively, organisms growing on culture media can be identified in minutes because the pre-processing steps required to extract the bacterial proteins are not required.
The identification process
To perform the identification, the protein extract or a small amount of a bacterial colony is transferred to a metal target plate then overlayed with a matrix that helps to protect and ionize the proteins. Within the MALDI-TOF instrument, the sample is bombarded with a laser which causes molecules in the sample to be desorbed and ionized by charge transfer. The molecules fly through a metal flight tube, where they become separated by their mass to charge ratio, then collide with a detector. A profile of the organism, called the mass spectrum, is generated and compared to a library of known organisms for identification.
Montefiore’s pathology department invested in the MALDI technology after a study published in the Archives of Pathology and Laboratory Medicine showed the substantial benefits of this technology when it was applied to blood cultures in a big hospital setting. That study, led by Dr. James Musser, MD, PhD, chair of pathology and genomics medicine at Methodist Hospital, in Houston, TX, used MALDI-TOF to quickly identify gram-negative bloodstream infections directly from positive blood culture bottles. Rapid identification and susceptibility techniques with antimicrobial stewardship significantly improved time to optimal therapy, and it decreased hospital length of stay and total costs.
Montefiore’s team conducted its own impact study in 2014 that looked at early implementation of MALDI-TOF identification coupled with antibiotic stewardship on time to optimal antibiotic therapy and outcomes in bacteremic patients. The study, led by Dr. Connie Park, an infectious disease specialist, looked at 115 blood cultures of adult inpatients at Moses, Wakefield and Weiler hospitals with a first episode of bacteremia identified during the study period. This work demonstrated that, overall, MALDI outcomes were timelier in 2014 than in 2013. In addition, the time to identify gram-negative organism using blood culture bottles was faster than plates, at 23 hours versus 52 hours. Furthermore, the involvement of the antimicrobial stewardship team at an earlier point in the management of these infections resulted in faster and more accurate treatment decisions by the physician.
While the cost savings are still being evaluated, Dr. Levi estimates the hospital could save approximately $100,000 per month based on an average of 200 blood culture tests. “Once you make the initial investment in the MALDI-TOF there is no substantial investment thereafter,” Dr. Levi said. “We think use of MALDI-TOF is important and is having a big impact on patient care.”