A Move Towards Precise Management of Bacterial Infections

Antibiotic resistance is a global challenge as it threatens our ability to treat common infections, as emphasized by WHO’s Assistant Director-General for Health Security, Dr Keiji Fukuda:

“Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill.”

Earlier in June, FDA clearance was declared for a procalcitonin (PCT) immunoassay, the LUMIPULSE® G1200 which was developed by Fujirebio Diagnostics, Inc.

To gain an insight into the implications of precise PCT measurement, we spoke with Chris Dague, Product Manager of Fujirebio Diagnostics, Inc. Chris explains how Fujirebio’s PCT assay offers an advantage over tests which have been traditionally used to identify bacterial infections, and its implications for individuals and hospitals.

How have bacterial infections and complications such as sepsis traditionally been identified, and what are some of the limitations of these methods?

CD: Combined with the clinical picture the patient presents, traditional tests have included blood cultures which have an extended turnaround time of 2-3 days with reduced sensitivity and specificity. Sputum cultures also have an extended turnaround time with a high number of false positives due to contamination. Other tests such as white blood cell counts also have a reduced specificity in identifying sepsis. Because these tests often take time and symptoms of bacterial and viral infections overlap, antibiotics can be mistakenly prescribed for viral infections.

What is PCT, and how can it be used as a clinical biomarker?

CD: The CDC estimates that 20% - 50% of acute care antibiotic prescriptions are unnecessary. Procalcitonin (PCT) is a biomarker specific to bacterial infections. PCT, together with the clinical picture presented, offers advantages as an aid to guide antibiotic treatment decisions or to assess the risk of critically ill patients for progression to sepsis or septic shock. By monitoring the change in PCT levels, antibiotic treatment can be ended more quickly reducing treatment days and costs. PCT can help physicians identify which infections should be treated with antibiotics, whether treatment is effective and when to end treatment.

What advantages does measuring PCT levels offer over testing for other biomarkers such as lactate and CRP?

CD: PCT has a high specificity for bacterial infections versus inflammation due to non-bacterial causes. It typically rises within 3-6 hours after infectious challenge and also correlates with the severity of the infection. PCT remains elevated until appropriate therapy is provided and declines as septic infection resolves.  CRP is also evaluated in inflammatory conditions not related to bacterial infections and has a delay in reaching elevated levels of 12-24 hours. Lactate is not specific to bacterial infections, but rather is associated with poor tissue perfusion, which can be caused by heart failure, hypotension, etc. The kinetics and bacterial specificity of PCT offer advantages over both CRP and lactate.

Can you tell us more about the Lumipulse® G B·R·A·H·M·S PCT assay, and the benefits it can bring to patients and clinicians?

CD: The LUMIPULSE G1200 B·R·A·H·M·S PCT assay features excellent precision, which is important when taking multiple measurements over time. Used in conjunction with other laboratory findings and the clinical assessment PCT aids:

• Decision making of antibiotic therapy for confirmed or suspected lower respiratory tract infections

• Decision making of antibiotic discontinuation for patients with suspected or confirmed sepsis

• Risk assessment of critically ill patients on their 1st day of ICU admission for progression to severe sepsis and septic shock

• Cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock

What role can tests such as this play in helping to meet antibiotic stewardship guidelines?

CD: Studies have shown that the use of PCT can help reduce the days of antibiotic therapy, hospital mortality from infection, 30-day readmission rates, hospital C-Difficile infections and adverse drug events from antimicrobials. These are all significant benefits to both patients and hospitals.

Chris Dague was speaking with Anna MacDonald and Michele Wilson, Science Writers for Technology Networks.