The treatment of a bacterial infection is typically a course of antibiotics. However, an antibiotic regimen should be optimized. The overuse of antibiotics for nonbacterial infections, such as viral infections, can lead to antibiotic-resistant strains of bacteria. Resistance can also develop when patients take antibiotics for too long a duration. Optimizing antibiotic use contributes to antimicrobial stewardship, which is treating the patient with right drug, dose, and duration. Molecular testing for respiratory and gastrointestinal infections has played an important role in distinguishing viral versus bacterial etiologies and has been previously reviewed in this article series. Importantly, clinicians also have biomarker point of care (POC) testing in their tool chest when managing patients for infection and sepsis. One such biomarker that is particularly informative is procalcitonin (PCT).
PCT is a useful biomarker to evaluate the presence of systemic bacterial infection, sepsis, and septic shock. PCT is released into the bloodstream as a response to the presence of bacterial toxins and is typically detected within 2-4 hours of sepsis onset. However, PCT is not significantly increased for viral infections, local bacterial infections, or other types of inflammation. The biomarker has a half-life of about 24 hours, and levels increase as the bacterial infection progresses and declines during patient recovery. Ranges of PCT values have been suggested for both initiating and discontinuing antibiotic therapy, based on PCT levels measured in nanograms per milliliter.
Elevated PCT levels that are considered false positive for systemic bacterial infection have been reported due to burns, circulatory shock, inhalation injury, severe trauma, and pancreatitis. Therefore, PCT use may have different applications, depending on the clinical scenario. PCT has been studied as a biomarker for the Emergency Room (ER), Neonatal Intensive Care Unit (NICU), and the management of patients with a SARS-CoV-2 (COVID-19) infection. The data in multiple studies demonstrate PCT is a useful biomarker as a POC test. PCT may be measured serially over time and can guide the clinician regarding antibiotic treatment. The PCT test is available at many onsite hospital labs, is available 24 hours a day, and typically has a stat turnaround time of < 2 hours. This is ideal compared to sending out to an external lab, where shipping alone can take at least 24 hours. PCT is measured by immunoassay techniques, and the Food and Drug Administration (FDA) has approved its use in respiratory infection for sepsis management in the United States.
The clinical utility of PCT testing as a POC test is clear in the literature. Reimbursement for PCT testing is about $27-$28 USD. Payors have policies on the medical necessity and application of PCT testing. AETNA considers PCT medically necessary for starting and stopping antibiotic therapy for patients in the Intensive Care Unit (ICU) or for admitted patients with respiratory infections to manage antibiotic use. Conversely, AETNA has many other indications where PCT measurement is considered investigational because of insufficient clinical evidence including a COVID-19 infection, sepsis after heart surgery, and early-onset neonatal sepsis, among others. While it is encouraging at least one payor has their PCT policy available online, more transparency is needed regarding payors, rates, and indications where it is medically necessary or considered experimental.
Implementing a PCT protocol may be challenging. It is not a test that should be universally ordered for all patients with an infection. Payors have specific indications where it will be reimbursed. Testing algorithms can be designed to prevent over-testing and to tailor antibiotic use. PCT’s clinical utility is dependent upon correctly identifying or ruling out patients with a bacterial infection. It is also informative to measure serially over time to track the progression or regression of a bacterial infection. The probability of an infection present in a patient could also impact treatment. For example, patients with a high probability of bacterial infection may be given antibiotics as a precautionary measure, whereas the low-risk patients may cause a clinician to withhold antibiotics until the PCT results are available and are indicative of a bacterial infection. PCT results should not be interpreted in isolation, other POC lab tests may be available, depending on the clinical situation. Furthermore, there are other variables like clinical history, symptom presentation, and environment (primary care, ER department, ICU, etc.) that impact decision making. Given that the test is most useful when results are available immediately, manual pre-authorization would be difficult to coordinate unless it was integrated into the electronic health record (EHR) with the ability to be approved very quickly. Clinicians should be aware of the evidence-based guidelines available for PCT testing, so they know when it’s appropriate to order.
PCT is an informative biomarker for bacterial infection management in the ER, ICU, and for patients with a bacterial respiratory infection. Executing a PCT protocol will take coordination among clinicians, the hospital laboratory, and payors. The clinician will need to use their best judgement by factoring in the details of their patient’s unique situation when deciding which POC tests to order. Fortunately, there is a tremendous amount of interest regarding the clinical utility of PCT in patient care and antimicrobial stewardship among clinicians and researchers alike. It will be interesting to see how PCT POC testing evolves with new and refined medical guidelines as more data is generated.
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AETNA medical Policy Number: 0771. Procalcitonin (PCT): http://www.aetna.com/cpb/medical/data/700_799/0771.html#:~:text=Aetna%20considers%20the%20measurement%20of,rates%20and%20duration%20of%20use.
CMS Lab Fee Schedule 2022. https://bassett.testcatalog.org/catalogs/191/files/6843
Children’s Minnesota: https://www.childrensmn.org/references/lab/chemistry/procalcitonin.pdf
University of Nebraska Medical Center: https://www.unmc.edu/intmed/divisions/id/asp/procalcitonin-pct-guidance/index.html
University of Pittsburgh Medical Center 2021 Clinical Diagnostic Laboratory Fee Schedule: https://www.upmc.com/-/media/upmc/healthcare-professionals/physicians/documents/lab-fee-schedule.pdf