By Wendy D. Wiesehuegel, MS, BSN, RN, CIC
In the short time that it takes to make my favorite meal, shrimp pad Thai (20 minutes), one equally rapid and reliable laboratory test, Procalcitonin (PCT), can quickly inform a licensed healthcare provider that their patient has a bacterial infection, not a viral infection, and halt a fatal outcome (BioMérieux, 2016; Food and Drug Administration, 2012; Lee, 2013; Pantelidou and Giamarellos-Bourboulis, 2015; Schuetz and Mueller, 2016). The untimely identification of antibiotic-resistant bacterial infections is the No. 1 cause of human deaths occurring from sepsis-related events and has increased three-fold over the last decade (World Sepsis Day.org, 2016). Antibiotic stewardship is a necessary fundamental in the battle against antibiotic-resistant infections and should be a priority for all healthcare facility types; antibiotic stewardship is not confined to hospitals (O’Brien and Gould, 2013).
Biomarkers with intense specificity such as Procalcitonin should be routinely used and part of your arsenal in antibiotic stewardship programs (Wong, 2016).
PCT is a normally occurring protein located on human chromosome 11 and encoded by the CALCI-1 gene (Jin and Khan, 2010; Nakamura, et al., 2013). PCT is present, but not detectable in healthy humans (Lin, 2015). The thyroid produces C-cells which in turn create the hormone, Calcitonin (Felsenfeld and Levine, 2015). Calcitonin maintains normal calcium levels in the body (Lin, 2015). PCT levels rise out of the endopeptidase-splitting- preprocalcitonin (2015). PCT increases above normal in a human approximately three to six hours after an endotoxin or mediator such as interleukin (IL)-1ß, tumor necrosis factor (TNF)-a, or IL-6 (Schuetz, et al., 2011b) is introduced when there is an inflammatory response (as in sepsis) and multi-organ dysfunction (FDA, 2016).
Procalcitonin Reference Ranges
PCT is directly correlated with infection severity and systemic bacterial load, therefore critically ill patients and those with community-acquired pneumonia (CAP) may be relieved of any potential fatal outcome with the use of PCT (Schuetz et al., 2011b). Normal reference ranges for PCT in children older than 72 hours and adults is 0.15ng/ml or less (Lin, 2015). Relevant studies conducted after the start of the new millennium to measure PCT showed that a level >1.2ng/ml, were always associated with bacterial infections, and with viral infections, PCT levels were in the lower ranges of 0.7, 0.8, & 1.1ng/ml (Delevaux et al., 2003).
Utilization of Procalcitonin in the Diagnosis of Sepsis and Infections
Historical Aspects of Procalcitonin
Historically, Procalcitonin was discovered in the human body in the 1970s, however, it was not until 1993 that the first clinicians, Asicot, Gendrel, Carsin, and Bohuon, formally conducted testing for the presence of PCT in humans related to sepsis and infections. PCT has been available in the U.S. since 1996 (Meisner, 1996), and often is used off-or-open-label (De Jong et al., 2016). In 2008, the FDA approved PCT use in the U.S. for sepsis and infection identification, however this was limited to ICU patients (Food & Drug Administration [FDA], 2008). Very recently, the FDA advisory committee (2016) met on November 10, 2016, to review Class II devices (21 CFR 866.3215) specific to the PCT test. This meeting was prompted after a request was received by BioMérieux, a test sponsor, who proposed that PCT testing must also include human lower respiratory infections (LRIs) and sepsis (FDA, 2016).
Other biomarkers are available that test for sepsis and infections, and many of which are medical mainstays. However, many other biomarker tests lack that one quality of specificity that PCT has that can identify whether an infection is bacterial or not. Other biomarkers used routinely are C-Reactive Protein (CRP), the traditional White Blood Cell count (WBC), cytokines, body temperature, and erythrocyte sedimentation rate (ESR) (Schuetz, et al., 2011a; Simon, et al., 2004). In one study conducted by Barati, et al. (2008), WBC, CRP and ESR were shown to be of “little value” in the diagnosis of burns and severe infections associated with burns due to that true infection signs may be masked by sepsis. The authors discussed that PCT was proven as highly decisive lab test criterion compared to all other biomarkers, with a sensitivity of 100 percent, and specificity of 89 percent in those burn patients diagnosed with sepsis.
To date, additional studies on PCT and sepsis/infection has shown to have a higher sensitivity and specificity than other biomarkers routinely used (Zhao, et al., 2014). Bacterial versus viral test results in animal surrogate and human research studies prove that a statistical significance for PCT specificity of 98 percent in animal research studies), and 92 percent in human research studies, as compared to 86 percent with CRP testing (human research studies) (1998; Liu, et al., 2015). There appear to be many facilities and providers unaware of Procalcitonin as a biomarker that can greatly assist with their antibiotic stewardship program and reduce antibiotic resistance in their patient populations. Education is lacking regarding that the use of this rapidly available test, or, that it is even a choice at their facility.
Procalcitonin and Antibiotic Stewardship
Appropriate antibiotic utilization for human patients is a priority for global public health organizations (World Health Organization [WHO], 2016). Research shows that empiric antibiotics provided for a viral infection are one of the leading causes of our current antibiotic resistance problem (Llor and Bjerrum, 2014; Gelband, et al., 2015; Chen, 2016). Diagnostic tests that look for evidence of early, acute sepsis and infection are of great importance. In the United States, the National Action Plan for Combating Antibiotic-Resistant Bacteria published by the White House (2015) indicates that aggressive action should be taken for research to include available diagnostic tests specific for pathogen identification, and sepsis and infection recognition. One of the primary goals stated by the White House is to “Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria” (page 2). The research request also included the necessity of “Point-of-need diagnostic tests to distinguish rapidly between bacterial and viral infections as well as identify bacterial drug susceptibilities” (page 5). PCT, a biomarker and protein precursor to the calcitonin hormone (Meisner, et al., 1998), is the only human biomarker at this time that is specific to bacterial infections and has been able to distinguish between bacterial/fungal and viral infections. Antibiotic stewardship programs that are not already using PCT routinely, could really use this type of test to improve patient outcomes with sepsis and infections.
Processing Procalcitonin in a Medical Laboratory
Laboratory testing for sepsis and infection identification can require lengthy processing before results are available (Gabler, 2015). Although according to the Infectious Disease Society of America (IDSA) and the American Society of Microbiology (ASM), lab cultures are still accurate lab test indicators if performed properly, for the diagnosis of bacterial and specific types of fungal infections, however, cultures remain problematic therefore initial and repeat culture results may not be reliable or cost-effective (Baron et al., 2013; Weinstein, 2008). Blood cultures have a 50 percent diagnostic failure rate and can take 24 to 48 hours to process (Pantelidou and Giamarellos-Bourboulis, 2015). Contamination rates are additionally well-published and address the errors made by medical staff in the collection of cultures. Multiple studies do, however, cite that when medical staff is trained how to properly draw and handle blood cultures and then observed, their performance decreases contamination rates; obviously the Hawthorne Effect is actively at work (another article for another day!). There are additionally lab tests available as gold standards for virus testing, such as antigen testing, or, acute- and convalescent-phase antibody titer testing (Liu, 2016), however, as previously stated, lengthy delays until these are resulted continue to be an issue.
Successful Patient Outcomes and PCT
The key to successful patient outcomes for appropriate antibiotic stewardship in sepsis and infections when testing for PCT is largely dependent on not only healthcare staff performance with collections, but also laboratory turnaround time (TAT) after the blood sample is collected (Lifshitz, 2016). Healthcare facility policies and procedures must reflect the urgency of collection and testing, and a PCT result should be on the critical lab result report list. So, what licensed health care provider would not want to have access or use an accurate, rapid lab test result for the initial identification or monitoring of a sepsis or infectious process until systemic resolution? Sadly, not many healthcare providers or facilities are aware of PCT or realize that the biomarker test is available; evidence shows that PCT is not in routine use in healthcare in the U.S. (Neviere, 2016).
PCT should be considered routinely as it is now known to decrease mortality (De Jong, 2016): “The combination of the first PCT level (= 2.0 ng/mL or > 2.0 ng/mL) at initial diagnosis of severe sepsis or septic shock with the patient’s clinical course and the change in PCT level over time until Day 4 provides important additional information about the mortality risk. The PCT level on Day 1 (the day after severe sepsis or septic shock is first clinically diagnosed) can be used to calculate the percent change in PCT level at Day 4 if the Day 0 measurement is unavailable (FDA, 2012; FDA, 2016).”
By instituting this simple lab test, PCT, into the protocols of health care antibiotic stewardship programs and tailoring these protocols to specific settings, inappropriate empiric prescribing of antibiotics may be prevented (Schuetz, et al., 2010). Make Procalcitonin a priority for review for your antibiotic stewardship arsenal.
Wendy D. Wiesehuegel, MS, BSN, RN, CIC, a veteran Naval officer, entrepreneur and germ huntress, is shocked to discover that after she became infected with hepatitis B in the military in the 1980s, an infection control nurse used her affliction to create a protégé, providing her with a lifelong passion disguised as a career. You can find Wiesehuegel “Partnering for Prevention,” where “No Organism is an Obstacle” at www.preventinfectionobstacle.org
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