Molecular Diagnostics and Sepsis

Molecular options could overcome the obstacles of diagnosing sepsis.

Vol. 25 • Issue 9 • Page 48

Molecular Diagnostics

Modern medicine is changing, and clinical laboratories aren’t just following suit-they’re leading the charge. The rise of molecular technologies in diagnostic testing has already made a substantial impact in areas like cancer research, but what about other dangerous conditions? Currently, sepsis is one of the most dangerous complications a patient can face in a healthcare facility, leading to approximately 200,000-300,000 deaths a year. How are clinicians and researchers working to utilize molecular diagnostics (MDx) to address complications from sepsis?

In a recent interview with ADVANCE, Peter Ward, MD, professor of pathology, inflammation and immunology at the University of Michigan School Of Medicine, discussed the potential threat of sepsis in patient outcomes. Sepsis typically comes as a result of a bacterial infection due to a perforation in the gut (either surgical or trauma-related) or pneumonia as a result of Pseudomonas, Klebsiella, or Staphylococcus-particularly methicillin-resistant Staphylococcus aureus (MRSA). Treatment options rely on antibiotics, but these are most reliable if applied quickly. Diagnostic testing has traditionally focused on lung scans, bronchoscopy and blood cultures, but there has been a shift to rapid polymerase chain reaction (PCR) and genomic assessments recently.

“Genomic testing for infectious agents actually goes back about five years, but these more rapid strategies have only been developed in the past year or two,” said Ward. “But, in the past five years, there have been genomic strategies using PCRs, using bronchoscopic fluids, in which the PCR systems have been designated to go after products from micro-bacteria and tuberculosis – because the ordinary culture strategies would take at least five days to get something going with culture and, even then, it wasn’t terribly reliable.”

Even today, the key to effectively treating sepsis is an early intervention – a large part of which relies on a quick diagnosis. According to Ward, the real problem here goes all the way back to the initial guidelines for sepsis and simply getting physicians and clinicians to agree on a more uniform diagnosis. Until such a time as these guidelines are updated or new standards are introduced, the best course available is to play it safe by treating all infections as a potential sepsis case. For patients in the emergency department (ED), this means that anyone with the basic risk factors presents a possible risk and should be examined as such.

“Sepsis can include a fairly large variety of different clinical situations, and there is a problem in clinicians agreeing on which individuals have the diagnosis of sepsis that would be commonly agreed upon,” explained Ward. “And, so, there’s a lot of attempt[s] to try to coordinate more uniform criteria for the diagnosis of sepsis.”

Another source of difficulty for hospitals, clinicians and diagnosing physicians is the presence of patients coming in from other healthcare facilities in which they may have already received preliminary treatments like broad spectrum antibiotics. These drugs throw off a patient’s respective levels, skewing the test results as false-negatives and, ultimately, stalling essential treatment. In order to prevent delayed treatment based of false data like this, there must be a focus on maintaining and updating complete patient data during the transition. In the meantime, PCR options provide an additional ­testing outlet for potentially septic patients.

“The other problem that has been around for quite some time is that, often, these patients are admitted from other medical facilities, and they’ve often been put on broad spectrum antibiotics,” continued Ward. “And, so, at least half of the patients that have been admitted, who will now be diagnosed as having sepsis, have blood cultures that are negative – or even sometimes bronchial secretions that are negative – and, in part, that’s often because they’ve been pre-treated with broad-spectrum antibiotics.”

Biomarker testing has also become a popular area of study in the healthcare industry. These provide an effective indicator of possible hereditary or ongoing conditions, but while the elevated presence of certain biomarkers can certainly provide insight into the severity of an infection or malignancy, biomarker testing currently lacks the ability to deliver a specific diagnosis. Essentially, given the large number and non-specific nature of biomarkers that spike as a result of sepsis, it can be misdiagnosed as a number of other possible issues. Because of this, it has become an important part of monitoring a condition but has a ways to go as a diagnostic option.

“Many of these biomarkers will go up after acute injury, after a burn injury, after pneumonia, but they’re totally non-specific,” said Ward. “They tell you the intensity of a medical condition, but they cannot definitively tell you that it’s sepsis or not.”

Much like the rest of the industry, the field of sepsis is in flux. Whereas there are distinctive genomic assessments and biomarker warning signs for diseases like melanoma, colon cancer and other cancers, there are not yet any clear indicators for sepsis. Molecular and biomarker testing options have become an important part of healthcare in recent years, however, and the technology continues to evolve – with the advent of PCR options, especially, presenting a new possible diagnostic approach. While MDx hasn’t necessarily fleshed out just yet in regards to sepsis, there remains quite a bit of hope for clinical professionals hoping to catch sepsis as early as possible to improve patient outcomes.

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