Procal 3 Software Download
Dona Vansoest
PCT has some advantages other biomarkers in common clinical use such as C - reactive protein (CRP) and white blood cell count. The advantages of PCT over older markers include: specificity for bacterial infection (versus inflammation in general), the rapidity of its rise after an insult (6 hours), the rapid decline with immune control on infection (half-life of 24 hours), excellent correlation with severity of illness (higher levels in more severely ill), and the lack of impact of anti-inflammatory and immunosuppressive states on production
Procalcitonin will be available 24 hours a day and will be run as needed. Stat order results will be available within 90 minutes while results of routine testing will be available during the same shift (usually 2-4 hours). A value of = 0.1 g/L will be flagged as elevated. Interpretation should be based upon the clinical context and algorithms available on the Antimicrobial Stewardship Website. The specific comment included on the laboratory report is included below:
Decisions on antibiotic use should not be based solely on procalcitonin levels. If antibiotics are administered, repeat procalcitonin testing should be obtained every 2-3 days to consider early antibiotic cessation. PCT is a dynamic biomarker and most useful when trends are analyzed over time in accompaniment with other clinical data. Interpretation should be based upon clinical context and algorithms available on the Antimicrobial Stewardship Website.
Sepsis: PCT levels of >2.0 g/L predicts sepsis and levels of >10 g/L indicate likely septic shock. Sensitivity and specificity of PCT for the diagnosis of sepsis has varied based upon population and underlying diseases. Higher PCT levels have been shown to be associated with a worse prognosis, but have not generally added to well validated clinical scoring systems such as APACHE or SAPS.
Renal Involvement in Pediatric Urinary Tract Infections: PCT values of >0.5 g/L have a sensitivity of 70-90% and 80-90% specificity for renal involvement in pediatric patients with UTIs.
Clinicians should consider the increased cost associated with the use of additional tests. PCT cost is approximately twice that of CRP, but provides greater clinical value in the overall management of the patient, especially when used for determination of cessation of antibiotics. A cost benefit analysis of PCT use in the ICU found cost savings or increased cost of care was dependent on how frequently PCT was utilized and the cost of the antibiotics which were discontinued.19 Any cost savings through the use of PCT will be realized through decreased antibiotic use and presumably decreased complications of antibiotic use (C. difficile infection, drug toxicity, etc.)
Excellent evidence supports the use of PCT for assisting clinicians in antibiotic management in LRTI including pneumonia, exacerbations of chronic bronchitis, and other assorted lower respiratory tract infections (bronchitis, asthma exacerbation, etc.). A meta-analysis of 8 studies with 3431 patients found the use of PCT in LRTI resulted in a 31% decrease in antibiotic prescriptions and a decrease in antibiotic duration of 1.3 days.17
Recommended Use: Based upon this evidence it is suggested that patients considered at risk for bacterial LRTI or being started on antibiotics have a PCT value measure on admission and every 2-3 days subsequently. Interpretation of values is listed below in Algorithms 1 and 2.
A number of randomized trials have been performed evaluating the utility of PCT levels in guiding antibiotic therapy. These have been summarized in 3 separate systematic reviews/meta-analyses showing a decrease in antimicrobial exposure of 19-38% without increases in mortality, length of stay, or relapsed/persistent infection.18-20 Most studies in sepsis have evaluated using PCT to discontinue antibiotics although one large trial did use PCT levels to assist in the decision to initiate treatment.7 Because of limited data, the decision to initiate therapy in the ICU should be driven by the severity of illness and clinical assessment of the likelihood of infection with the PCT used as an adjunct to assist in the decision to initiate antibiotics. Much more rigorous evidence exists to support the use of PCT to discontinue antibiotics.
Recommended Use: Based upon the above information it is recommended that patients admitted to the ICU with presumed sepsis/septic shock/etc have PCT drawn on admission and that PCT be repeated on the next 2 days. Decisions regarding antibiotic therapy can then be made based upon PCT dynamics, culture data, and patient specific clinical data. Further PCT values may be drawn at the discretion of the physician.
In current clinical practice, procalcitonin (PCT) has developed into a promising new biomarker for the early detection of systemic bacterial infections. PCT is a 116-amino acid residue first explained by Le Moullec et al. in 1984; its diagnostic significance was not recognized until 1993.[1] In 1993, Assicot et al. demonstrated a positive correlation between high serum levels of PCT and patients with positive findings for bacterial infection and sepsis (e.g., positive blood cultures). Further, they demonstrated that PCT did not elevate in viral infections and that serum levels of PCT would decrease following the administration of appropriate antibiotic therapies.[2]
Other inflammatory biomarkers, such as C-reactive protein, lack the specificity to accurately distinguish between bacterial and non-bacterial infections.[3] Therefore, PCT assays, with a specificity of 79%, have been developed and utilized to more accurately determine if a systemic inflammatory reaction is caused by a bacterial species.[4]
The United States Food and Drug Administration has approved using PCT assays for initiating or discontinuing antibiotics in lower respiratory tract infections (LRTIs) and for discontinuing antibiotics in patients with sepsis.[5] Numerous studies have evaluated PCT-based treatment algorithms in these settings and found them safe compared to standard care.[6] In particular, using PCT assays allows cessation of antibiotic therapy without increased morbidity and mortality. This makes PCT a potentially helpful tool for preventing the emergence of antibiotic-resistant organisms while still ensuring appropriate treatment for serious bacterial infections.[4]
PCT should not be used as the sole determinant for antimicrobial therapy.[7] The results of a PCT assay should be placed in the context of the clinical scenario considering the possible site of infection, the likelihood of bacterial infection, the severity of illness, and other pertinent clinical data.[8]
Under normal homeostasis, pre-procalcitonin undergoes initial synthesis by thyroid C cells. Later this peptide is transformed into procalcitonin via cleavage of a 25-amino acid signal sequence by endopeptidases. The end product calcitonin, the 32-amino acid hormone responsible for serum calcium regulation, is formed following conversion by the enzyme prohormone convertase.[9] Typically, physiological conditions result in very low serum PCT levels of less than 0.05 ng/mL. However, the synthesis of PCT can be increased up to 100 to 1000 fold due to circulating endotoxins or cytokines such as interleukin (IL)- 6, tumor necrosis factor (TNF)-alpha, and IL-1b, which act on various tissues.[10]
The extra-thyroid synthesis of PCT occurs in the liver, pancreas, kidney, lung, intestine, and leukocytes; notably, the synthesis of PCT is suppressed within these tissues in the absence of bacterial infection.[11] In contrast, cytokines released following viral infection, such as interferon (INF)-gamma, will lead to the down-regulation of PCT, thus highlighting another advantage of PCT assays.[12]
Human serum or plasma specimens can be used to determine procalcitonin (PCT). For accurate results, serum and plasma specimens should be free of fibrin, red blood cells, and other particulate matter.[13] Serum specimens from patients receiving anticoagulant or thrombolytic therapy may contain fibrin due to incomplete clot formation.[14] Using heat-inactivated specimens, pooled specimens, grossly hemolyzed specimens, specimens with obvious microbial contamination, and specimens with fungal growth is not recommended. The use of plasma is recommended for rapid turnaround of results.[15]
The PCT specimens should be free of bubbles. Remove bubbles with an applicator stick before analysis. Use a new applicator stick for each specimen to prevent cross-contamination. To ensure consistency in results, recentrifuge specimens before testing if they contain fibrin, red blood cells, or other particulate matter.[16] The EDTA plasma and serum specimens stored frozen at -70^oC or colder have demonstrated stability for up to 18 months.[17]
Procalcitonin (PCT) serum levels have been shown to increase 6 to 12 hours following initial bacterial infections and increase steadily in the two to four hours following the onset of sepsis.[18][10] The half-life of PCT is between 20 to 24 hours; therefore, when a proper host immune response and antibiotic therapy are in place, PCT levels decrease by 50% over 24 hours.[11]
In current clinical practice, several chemical assays have been developed to detect PCT serum levels at varying sensitivities, most displaying functional sensitivity around 0.06 ng/mL.[3] One of the first commercially available assays was a homogenous immunoassay that utilized time-resolved amplified cryptate emission technology.[12] The assay comprises a sheep polyclonal anti-calcitonin antibody and a monoclonal anti-katacalcin antibody which binds to the calcitonin and katacalcin amino acid sequence of PCT via the sandwich method. The assay uses 20 to 50 mL of plasma or serum and takes 19 minutes to complete; results are typically obtained within one hour following the serum draw.[19]
All currently available assays for the quantification of PCT are based on immunoassay techniques.[13] The chemiluminescent microparticle immunoassay (CMIA) technology is used to quantitatively determine PCT in human serum and plasma.[20] Samples and anti-PCT-coated paramagnetic microparticles are combined and incubated. The PCT present in the sample binds to the anti-PCT-coated microparticles. The mixture is washed. Anti-PCT acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, pre-trigger and trigger solutions are added.[21] The resulting chemiluminescent reaction is measured as relative light units (RLUs). There is a direct relationship between the amount of PCT in the sample and the RLUs detected by the system optics.[20]
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