For sepsis Dx, MDW biomarker brought into the mix

The infectious disease physicians suggested that the laboratory put a T2 kit together with a hold tube up front, but not run the MDW unless needed. “You draw it at the same time you draw the blood culture but from a separate draw—not out of a line but out of a vein. We have a reflex setup for when the MDW is high [above 20]. That, plus an abnormal WBC, alerts the microbiology lab to run the T2,” Dr. Patterson says. “Otherwise we just don’t use it; it gets discarded. That way, we don’t run a lot of unnecessary T2s.” Using this algorithm, he adds, allows for faster results to physicians, a better subset of patients selected for testing, and more appropriate antibiotic use.

He reports that a study of MDW stratification by diagnosis at three large EDs in the U.S. (Crouser ED, et al. Crit Care Med. 2019;47[8]:1018–1025) has been replicated in a Johns Hopkins Hospital study (Malinovska A, et al. J Am Coll Emerg Physicians Open. 2022;3[2]:e12679) and in Europe in the previously cited study of two large EDs in France and Spain (Hausfater P, et al. Crit Care. 2021;25[1]:227). All studies found that, based on sepsis-2 or sepsis-3 criteria, an MDW value of 20 is effective for sepsis detection, during the initial ED encounter, he says.

Dr. Patterson shared a few cases to illustrate Butler’s early experience in shortening time to diagnosis and appropriate therapy. In one, a 67-year-old male admitted with hypotension and altered mental status had no sepsis indicators but had an MDW of 23.98 and WBC of 24.7. A T2 test found P. aeruginosa, confirmed two days later by blood culture. The WBC plus MDW values saved 37 hours to targeted therapy.

In another case, a 70-year-old male with shortness of breath was admitted with hypothermia and hypertension and no sepsis indicators. He had a WBC of 23.2 and MDW of 23.05 and the T2 detected E. faecium, confirmed by blood culture 20 hours later, thus shortening time to targeted therapy by 20 hours.

In a third case, a 57-year-old female with altered mental status arrived at the ED with hypotension but had a WBC of 21.9 and MDW of 21.55 with a T2-detected S. aureus infection. In her case, the ED was able to get to targeted treatment 14 hours earlier than normal.

The shortened time to a species-specific diagnosis in these cases is actually even greater, Dr. Patterson says, “as these are times to a positive Gram stain on a culture rather than the complete species identification.”

“We have thousands of patients now on whom we’ve done this and this is a preliminary look at a few,” he says. The potential positive outcomes from use of MDW, in addition to an earlier, more appropriate treatment course, include an improvement in care through a shorter length of stay and fewer “bounce back” patients.

Based on the experience so far, Dr. Patterson reports that the hospitalists want to bring on MDW hospitalwide. That is the plan now. “We are about to go ahead and open MDW whole-house.” The laboratory has opted to stay with 20 as the cutoff value. “We thought if we were getting too many positives and not enough yield, we could raise it to 21. But that hasn’t turned out to be necessary.”

Ahead lies a potential expansion of the diagnostic algorithm. One possibility is use of technology from MeMed, maker of host immune response diagnostics. In a recent presentation to Dr. Patterson’s laboratory, “the company reported going through thousands of inflammatory markers like procalcitonin to come up with a group of markers that might help physicians decide if somebody does have a bacterial infection. And they have identified three of them, including tissue necrosis factor-related apoptosis-inducing ligand, interferon-gamma release assay, and C-reactive protein. I’d like to validate it and see how it works in our hands, but it’s potentially interesting.”

Also interesting is discovering what the cause of sepsis is, Beckman CMO Dr. Vucetic says. “We have collaborated and partnered with other companies that are differentiating between bacterial and viral infection as they develop what’s important in diagnosis.”

The standard tests used to assess sepsis risk are valuable, Dr. Patterson says. “When your white cell count goes up, your other inflammatory markers go up. It seems that when there is an infection, it causes activation of the monocytes that are already circulating in the body. So it doesn’t require a bone marrow response.” Sometimes lactate and procalcitonin are normal when they’re checked, but the MDW may not be. “We’ve even had cases where the white count was normal and everything else was normal except the MDW was high.”

Research has shown a gap, he says, between the sensitivity of MDW and that of inflammatory markers like lactate. The 2019 study by Crouser, et al. (Crit Care Med. 2019;47[8]:1018–1025), found a sensitivity of 0.75 for WBC, 0.79 for MDW, and 0.85 for MDW and WBC combined, while lactate sensitivity was 0.59. “Choosing the MDW gives you the largest yield in terms of detection,” Dr. Patterson says of the findings.

As to cost, the T2 is reimbursable, “but it does cost a bit more to run than you get reimbursed, for some unknown reason,” he says. “That’s another reason to try to limit it. You don’t want to do it on everyone.”

Beckman Coulter’s MDW parameter is used more widely in Europe than in the United States. It takes time to build awareness of a new parameter in laboratories and clinics, says Beckman’s Jeff Tarmy. And laboratories need a Beckman instrument to use MDW. Even for those with the instrument, “there is a significant time commitment that goes into researching, validating, and rolling out new tests. This can be a meaningful hurdle for labs that are already challenged with staffing shortages and tightening financial resources.”

“But MDW is a great tool that can overcome this legacy of poor adoption because it doesn’t need a discrete physician order to be reported and Beckman Coulter is equipped and experienced to support the clinical implementation of MDW,” Tarmy says. He says more than 300 sites in North America are using MDW.

The company continues to drive awareness and adoption of the parameter, Tarmy says. He agrees with the business analysts who project a significant increase in the sepsis diagnostics market over the next 10 years. Beckman will continue to expand its menu of tests, he says, and believes MDW has a big role to play in diagnosing and managing sepsis. The company’s objective is to expand the CBC’s value. “We believe there’s more clinical data available in the CBC, the most prescribed diagnostic we have. That is where we look at novel biomarkers,” he says.

Anne Paxton is a writer and attorney in Seattle.