New Test Discriminates Between Microbial Infections and Sterile Trauma

Researchers have made an important breakthrough in efforts to develop a test to help clinicians determine whether a patient has a microbial infection or sterile trauma, a new study shows.

Mark Cartwright, PhD, from Harvard University, Boston, Massachusetts, and colleagues published the results of their study online in EBioMedicine.

The new test “offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated,” the authors write.

According to Dr Cartwright and colleagues, determining whether a patient has a microbial infection remains challenging. Although detecting the presence of bacterial infection in blood is the current gold standard for diagnosis of systemic infection, more than 70% of patients with sepsis have negative blood cultures. In addition, measurement of biomarkers of inflammation, such as C-reactive protein (CRP), is of limited value in patients who have inflammation associated with non-infectious illnesses or trauma.

The researchers therefore set out to develop a simple and rapid test that might help to triage patients, accelerate antibiotic administration, and identify patients who need sepsis therapies. They aimed to produce a test to recognize pathogen-associated molecular patterns (PAMPs)—molecules found in prokaryotes (such as bacteria and fungi) that are recognized by cells of the innate immune system.

They developed an enzyme-linked lectin-sorbent assay (ELLecSA) to quantify PAMPs in samples of whole blood from patients. The ELLecSA is a modified enzyme-linked immunosorbent assay (ELISA) that uses FcMBL (a protein that binds PAMPs) instead of an antibody immunosorbent.

The study showed that the new assay was a rapid, sensitive, and specific test to differentiate between patients with microbial infections and those with sterile trauma.

Within one hour, the assay detected PAMPS associated with more than 85% of all living pathogen species tested, including 14 of 16 bacterial species that are most commonly associated with sepsis.

In animal studies, the assay detected the presence of active infection in rats, even when blood cultures were negative and bactericidal antibiotics were administered. And in pigs, the assay not only detected infection, but was able to track infection, regardless of blood culture results.

Dr Cartwright and colleagues then evaluated the potential for the assay to be used as a diagnostic tool to identify patients who are at risk for sepsis. They showed that it was able to detect PAMPs in more than 80% of blood samples from emergency department patients with clinically-suspected sepsis, even though less than 20% of these patients had blood cultures that were positive for bacteria. The assay also differentiated infection from trauma-associated inflammation with a higher specificity than CRP.

This “simple test for diagnosing systemic infections has the potential to provide clinically actionable information to inform physicians when patients should be hospitalized, antibiotic therapies administered, or dialysis-like therapies initiated, even when blood cultures are negative,” the authors write. “It also could potentially be used to detect when bactericidal therapies are effective in vivo (i.e., by detecting an abrupt increase in PAMPs immediately following initiation of antibiotic therapy),” they conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.