Rapid ID from positive blood culture: Labs tally gains

Anne Paxton

March 2021—Fresh from its Dec. 27, 2020 FDA clearance, the Bruker MALDI Sepsityper Kit US IVD promises to provide microbiology laboratories with a universal, rapid sepsis identification solution. With the Bruker MALDI Biotyper platform’s reference library covering 491 organisms, the Sepsityper’s ability to identify pathogens directly from positive blood cultures in suspected bacterial or fungal sepsis cases delivers an “order of magnitude increase” in the number of microorganisms that can be identified through PCR detection, said Wolfgang Pusch, Bruker Daltonics executive vice president of microbiology and diagnostics, in a company statement.

But that’s no news to the microbiology laboratories in the United States that were early adopters of the Sepsityper Kit and have long taken advantage of its ability to return a pathogen identification in less than 30 minutes from a positive blood culture bottle alert. Finding that this feature can save up to 24 hours in time-to-result for many identifications, these laboratories started using Sepsityper more than six years ago when it was labeled research use only.

“A lot of laboratories are realizing they need to use MALDI-TOF MS technology for microbial identification,” says one early adopter, Ike Northern, MT(ASCP)SM, director of infectious disease testing and immunology for CompuNet Clinical Laboratories in Ohio, which acquired a MALDI Biotyper in 2015. He has found that using the MALDI Sepsityper Kit 50 on the Biotyper is a more cost-effective means of fast identification than PCR syndromic panels.

For Tekita Mckinney, MT(ASCP), MEd, infectious disease and PCR laboratory manager at Le Bonheur Children’s Hospital in Memphis, Sepsityper was the main reason her laboratory bought its MALDI-TOF instrument in 2012.

Mckinney’s laboratory performs some 80,000 tests per year for pediatric patients throughout the mid-South. Before she heard about Bruker’s MALDI-TOF in 2011, the laboratory was aiming for two improvements.

“We’re a small pediatric hospital but we take care of west Tennessee and also Mississippi, Arkansas, and Georgia. Our patients are very sick. With almost half of our 255 beds being critical care beds and with such a high acuity rate, we need to be able to reliably identify organisms, especially in blood cultures and other cultures, quickly. You’re talking about babies who may weigh only a couple of pounds and are fighting for their lives.”

“Patients may come to the ED with fevers, and we take a blood culture and send them home.” Typically the culture takes two days to become positive. “After that, we’re not seeing many positives.” But a positive would mean emotional turmoil for a child’s family while the pathogen was being analyzed. “We would call to say, ‘Your baby may be septic; you need to come into the hospital.’ We would hook the child up to IV antibiotics. And 18 to 24 hours later we may say it’s a contaminant, not a pathogen.” Her laboratory wanted to be able to reduce the chances of that happening.

It also wanted to lessen the risk of resistance patterns. “You don’t want that starting out on day 30 of life,” Mckinney says. “By being able to identify things more quickly, we are able to intervene early and keep our kids on mild organism-targeted antibiotics and keep the resistance patterns from starting while they’re here.”

She met with instrument makers and soon convinced the hospital’s infectious disease physicians of the need for Bruker’s MALDI Biotyper, which was up, running, and reporting out clinically by February 2013, aided by the Vitek for antimicrobial susceptibility testing and Bactec FX for blood culture monitoring. Now, with the Sepsityper Kit 50, once the lab has a positive blood culture, “within the hour we will know what is causing the problem,” Mckinney says.

“Before the Biotyper was FDA approved, we had validated 80 percent of the organisms we would see in a positive blood culture here at this hospital. Now that they’ve added the FDA-approved library, we’re completely covered,” Mckinney says. Some organisms can be seen in adults that don’t tend to appear in kids, she notes, so her lab doesn’t have all the resistance patterns and organisms that adults would see. “But everything we need, we have it with this instrument. With this new technology, even though there is a waiting period until the organism grows, once it grows or is identified in a blood culture environment, then you’re down to minutes. This means that a person in the hospital can maybe go home a day earlier.”

With the Biotyper, she explains, “you can perform the direct colony method from any agar plate” and get an identification from the MALDI. “If we have an organism we can identify with just drop biochemicals, like Staphylococcus aureus, we could do the drop test. We wouldn’t necessarily put that on the MALDI. But if we had a Gram-negative rod that we couldn’t identify with biochemicals, we would use the MALDI. And in a few minutes, we would know what we are dealing with. We’ll put the identification in the computer instead of the susceptibility. So there again, we’re still a day ahead.”

Le Bonheur’s infectious disease laboratory has one MALDI-TOF bench operating 24 hours a day with two people reading on day and night shifts. “By 3 AM, the doctors know everything we know. So they don’t have to call us at 7 AM. It’s already documented in the chart.”

The payoffs from these time savings are so substantial that they make the upfront cost of the MALDI-TOF of minimal importance, Mckinney says. “We save so much money from not having to bring the patient back to the hospital to hook up to IVs for 24 hours. And it’s not a lot out of our pocket because the consumables for this instrument are minor. We buy the Sepsityper Kit and the standard consumables, but it pays for itself in our being able to deliver this excellent patient care.”

Her laboratory could well expand its MALDI uses in the future. “We’ve done preliminary type things that we haven’t implemented yet, just having research students look at urines and spinal fluids tested directly on the MALDI-TOF,” Mckinney says. “We’re always interested in new technology here. As the hospital brings on more transplant children and others, the needs grow and change. So we try to grow with it.”

The microbiology laboratory at CompuNet Clinical Laboratories, which is a regional reference lab and a core lab for Premier Health System, runs 60,000 blood cultures per year. CompuNet was not one of the first in line to buy a Bruker Biotyper, but that was not for lack of trying.

“We kind of struggled with getting good identifications for some organisms, just because there weren’t great methods out there to identify them,” Northern says. “The Bruker MALDI-TOF was in the budget for three years before the administration approved it.” But in 2015, “they finally gave me approval. And we’ve been super happy with it.” His laboratory is now contemplating acquiring a second instrument.

Standard culture samples as well as positive blood culture samples can be analyzed on the same MALDI Biotyper; they just entail different processes for getting the sample ready to put on the instrument, Northern explains. “If you’re working off of a plate, as with a urine culture, you pick up some of the colony from the organism right off the plate and put it on the target plate. But when you’re working with the Sepsityper, your organism is in the blood, so you have to process your sample to concentrate the organism in order to put it on the MALDI-TOF. So it uses different parameters when it knows that it’s the Sepsityper versus a colony.”

About two years ago, his laboratory began to use the Sepsityper Kit 50 to get a rapid identification from a positive blood culture bottle. That’s been one of the areas of biggest impact, Northern says.

“Initially, we wanted to just be able to identify the organisms, the Gram-negative bacilli and staphylococci and so on, that our MicroScan, which we were using for susceptibility testing, could not identify. If we did a MicroScan and got a low probability ID, we’d have to do an API or some other method for identification. We had a special kit for Neisseria, a special kit for non-fermenters, a special kit for yeast. And we wanted to try to eliminate as many of those things as possible.”