Rapid ID from positive blood culture: Labs tally gains

Next they began to test Nocardia and Actinomyces and the results were good, Northern says. “But where the Biotyper helped us the most on our identifications was with anaerobes.”

Pre-MALDI-TOF, “we’d have to take the organism and streak it out and put it in three different environments to see if it was an anaerobic organism. And once you did that, you had to take another day to identify it. So it took two additional days to get an identification once you saw that organism on the plate.” In the year after acquiring the MALDI-TOF, “we were getting identifications on the first day.” That enabled the lab to cut the staff needed to do those anaerobic cultures each day from two to one.

Instead of doing aerotolerances, “we just identified everything on the plate the first day with the MALDI-TOF. All identifications of yeast are done on the same day, which is two or three days quicker than what we had before.” Identifications of mycobacteria, fungi, and molds will also soon be online, he says.

At an upfront cost of roughly $200,000, the MALDI-TOF looks like an expensive instrument, and it is, Northern admits, even though it fits on a tabletop. “But in a hospital environment, it’s pretty easy to justify that expense. You can save several thousands of dollars per patient by reducing their length of stay by even one day. So it doesn’t take a lot of patients for you to recoup that money.”

Using the Sepsityper Kit 50 is less costly than using a large PCR panel, he says. An analysis of CompuNet’s 60,000 blood cultures in 2019 found 6,600 positive blood cultures, an 11 percent positivity rate. Comparing the cost of analyzing half of those PBCs with a Sepsityper Kit (at $9.50 per test) versus half with a multiplex PCR test (at $105 per test) reveals a dramatic difference in cost-effectiveness.

Even adding in the tech time needed for the Sepsityper Kit 50, at an annual cost of $38,000, the savings from using the Sepsityper rather than the PCR test was $277,150 in a year’s time.

Recently added options have enhanced the MALDI’s usefulness, Northern says. “Bruker has a new [MBT Subtyping] module that allows you to do subtyping. So if you have an outbreak in your hospital—say you had five cases of Staph aureus that you think may be a nosocomial infection—you can take those five isolates and do the subtyping using the MALDI and tell whether it’s the same organism or not.” In the past, “we’d have had to send those off to different laboratories to do other types of tests.”

Bruker is continuing to develop that module as well as a module to detect other resistance markers. “When you have a resistance gene, it’s going to change the structure of the proteins, and if we can figure out exactly what those proteins are and where you can find them on the mass spectrometer, eventually we will be able to pick out resistant organisms when we put them on the MALDI.”

CompuNet conducted a validation study of the Sepsityper Kit 50 in 2017 using the Biotyper when it was still research use only. The purpose was to verify the rapid identification ability of the system from positive blood culture bottles. Parallel identifications were performed on 106 PBC bottles once the bottle flagged positive on the blood culture instrument: one using the Sepsityper Kit 50 and the other using MALDI-TOF and conventional biochemical ID from solid media.

The laboratory obtained accurate identification in 87 of the 106 PBCs (82 percent), and 74 of the identifications, or 70 percent, were identified to the species level while 13 (12 percent) were identified to the genus level. The study demonstrated that the Sepsityper Kit 50 using MALDI-TOF technology is a suitable method for rapid identification from PBC bottles, Northern says.

Is it possible that the MALDI could eventually replace most identification testing in the microbiology lab? “I would say if you had enough MALDI-TOFs, you could replace 90 percent of it,” Northern estimates. “Right now we don’t have enough room in our MALDI-TOF to do all of our identifications. So we still use our MicroScan for identifications for most of our Gram-negative rods. We’d need one or two more MALDIs to do all of our identifications.”

One potential pitfall of the MALDI’s identification process, Northern says, is getting a decent sample. “If it grows on a plate, most of the time we’re going to be able to identify it on the MALDI-TOF. But some different types of culture media are not always validated for use on the MALDI-TOF.” He and colleagues have done their own validation of four or five other culture media commonly used by the laboratory.

Some microbes can be trickier to identify using a MALDI, Northern says. “It seems like there are a couple of organisms that might be a bit more finicky to work with and didn’t identify quite so well.” But it’s more likely to be a question of the quality of the sample, in his view. “I think mostly it’s because those blood cultures had a low number of organisms in the sample to begin with.” While there are some organisms the lab has been unable to get the Biotyper to identify—for example, the MALDI-TOF in general cannot differentiate between Shigella and Escherichia coli—“it’s been far fewer than with our old methods.”

Case studies written by one of CompuNet’s infectious disease physicians show how the Bruker Sepsityper solution had effectively helped a patient with postsurgical complications, another with a history of heroin drug use, and a third with weakness and failure to thrive. In the first case, there was a quick identification with the Sepsityper Kit 50 “and the physician was astute enough to realize that the patient had had the same organism [Enterobacter cloacae] months before, a carbapenemase-producing organism,” Northern says. “So they put the patient immediately on antibiotics to treat a resistant organism. Without the Sepsityper, it would have taken them two more days to figure that out.”

In the case of the patient with a history of heroin use, when blood cultures were positive for Gram-positive cocci based on Gram stain 18 hours after admission, the admitting hospital assumed endocarditis, due to the patient’s history, and ordered a transesophageal echocardiogram to evaluate further. But one hour later, the Biotyper with Sepsityper Kit 50 identified Streptococcus pyogenes. That bacteria indicated, instead, targeted treatment with ampicillin and an ultrasound of the patient’s arm, which revealed extensive thrombosis of the axillary and subclavian vein. The patient had a good clinical response after six weeks of IV ampicillin.

Similarly, therapy for a 77-year-old admitted to the emergency department for weakness and failure to thrive was initially vancomycin and piperacillin-tazobactam. But blood cultures were positive for Gram-positive cocci on the first day of hospitalization. Shortly afterward, the Sepsityper Kit 50 results showed Enterococcus faecalis. So within 24 hours of admission the patient was switched to ampicillin and gentamicin, on which she remained for six weeks without issue.

The average physician, Northern says, may not be quick to change therapy based on just an identification off the MALDI-TOF or the Sepsityper. “But your infectious disease physicians are thrilled by this.” When he began to have discussions at CompuNet about acquiring a MALDI-TOF instrument, they wanted to see reduced use of antibiotics or use of more appropriate therapies. “But I told them there were studies to show that if you did these rapid identification methods and you don’t have a mechanism to make sure that someone makes a change when you get the positive result, it doesn’t make sense” to acquire a MALDI-TOF.

“The facilities that had someone who would get the result and take action on it saw significant changes in treatment,” Northern says. As a result, CompuNet took care to have the antibiotic stewardship committee work with the pharmacists. “They came up with a process that works well for our system. They’re taking action on the results quickly after they get them.”

The experience at Le Bonheur in Memphis is similar, Mckinney says. “We always ask the physicians what they are getting from the microbiology laboratory that they are most proud of,” she says. “And they always say the MALDI-TOF. They say it has changed how they can get their jobs done.”

Anne Paxton is a writer and attorney in Seattle.