Procalcitonin Threshold Research Articles

Procalcitonin level threshold and antibiotic use in patients receiving chimeric antigen receptor T-cell therapy

ABSTRACT Background: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy are vulnerable to infection and sepsis. Treatment course is frequently complicated by cytokine release syndrome which is often clinically and biochemically indistinguishable from sepsis. Procalcitonin (PCT) levels have been examined as a promising biomarker for infection in this cohort of patients. Methods: In this study, we measured daily PCT levels for patients for fourteen days (or hospital discharge) after receiving CAR T-cells to determine threshold PCT values specific for infection compared to those without infection. Results: We present preliminary results of our enrolled cohort to date (sixteen patients). Infection was present in only 12.5% of patients. However, those diagnosed with sepsis had elevated PCT levels with a peak mean of 2.6 µg/L observed on the seventh day post-treatment compared to those without infection remaining below 0.5 µg/L. Furthermore, we observed a trend for early and liberal antibiotic administration within our cohort. Conclusion: Our study highlights the challenges of antimicrobial stewardship in managing CAR T-cell therapy recipients. Our preliminary results underscore the utility of PCT in the risk-stratification and diagnosis of those patients at high risk for infectious complications after receiving CAR T-cell therapy and continue to advocate for a PCT threshold of 1.5 µg/L for diagnosing sepsis. Additionally, in the setting of CRS and lymphodepletion, where white cell count and CRP value are unreliable, a PCT value of < 0.5 µg/L may help exclude sepsis.

Procalcitonin and Risk Prediction for Diagnosing Bacteremia in Hospitalized Patients: A Retrospective, National Observational Study.

Bacteremia is associated with significant morbidity and mortality. Timely, appropriate therapy may improve clinical outcomes, and therefore, determining which patients benefit from more comprehensive diagnostic strategies (i.e., direct specimen testing) could be of value. We performed an assessment of procalcitonin (PCT) and clinical characteristics in the discrimination of bacteremic hospitalizations. We analyzed 71,105 encounters and 14,846 visits of patients with bacteremia alongside 56,259 without an admission. The area under the receiver-operating characteristic (AUROC) curve for the prediction of bacteremia via procalcitonin was 0.782 (95% CI 0.779-0.787). The prediction modeling of clinical factors with or without PCT resulted in a similar performance to PCT alone. However, the clinically predicted risk of bacteremia stratified by PCT thresholds allowed the targeting of high-incidence bacteremia groups (e.g., ≥50% positivity). The combined use of PCT and clinical characteristics could be useful in diagnostic stewardship by targeting further advanced diagnostic testing in patients with a high predicted probability of bacteremia.

Procalcitonin for Detecting Culture-Positive Sepsis in Neonates: A Prospective, Multicenter Study

Introduction: It is unclear if serum procalcitonin (PCT) estimated at sepsis suspicion can help detect culture-positive sepsis in neonates. We evaluated the diagnostic performance of PCT in culture-positive sepsis in neonates. Methods: This was a prospective study (February 2016 to September 2020) conducted in four level-3 units in India. We enrolled neonates suspected of sepsis in the first 28 days of life. Neonates with birth weight <750 g, asphyxia, shock, and major malformations were excluded. Blood for PCT assay was drawn along with the blood culture at the time of suspicion of sepsis and before antibiotic initiation. The investigators labeled the neonates as having culture-positive sepsis or “no sepsis” based on the culture reports and clinical course. PCT assay was performed by electrochemiluminescence immunoassay, and the clinicians were masked to the PCT levels while assigning the label of sepsis. Primary outcomes were the sensitivity, specificity, and likelihood ratios to identify culture-positive sepsis. Results: The mean birth weight (SD) and median gestation (IQR) were 2,113 (727) g and 36 (32–38) weeks, respectively. Of the 1,204 neonates with eligible cultures, 155 (12.9%) had culture-positive sepsis. Most (79.4%) were culture-positive within 72 h of birth. The sensitivity, specificity, and positive and negative likelihood ratios at 2 ng/mL PCT threshold were 52.3% (95% confidence interval: 44.1–60.3), 64.5% (60.7–68.1), 1.47 (1.23–1.76), and 0.74 (0.62–0.88), respectively. Adding PCT to assessing neonates with 12.9% pretest probability of sepsis generated posttest probabilities of 18% and 10% for positive and negative test results, respectively. Conclusion: Serum PCT did not reliably identify culture-positive sepsis in neonates.

Influence of Renal Dysfunction on the Differential Behaviour of Procalcitonin for the Diagnosis of Postoperative Infection in Cardiac Surgery.

procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p &lt; 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.

Diagnostic Accuracy of Procalcitonin upon Emergency Department Admission during SARS-CoV-2 Pandemic.

HighlightsProcalcitonin has low sensitivity for bacterial pneumonia at emergency admission.Procalcitonin has low specificity for bacterial pneumonia at emergency admission.Procalcitonin sampled at emergency admission should not guide antibiotic prescriptions.Higher procalcitonin values in COVID-19 pneumonia hinder its use for antibiotic stewardship.No procalcitonin cutoff level provided reliable guidance in antibiotic prescription.Introduction: Procalcitonin is a marker for bacterial diseases and has been used to guide antibiotic prescription. Procalcitonin accuracy, measured at admission, in patients with community-acquired pneumonia (CAP), is unknown in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Objectives: To evaluate the diagnostic accuracy of procalcitonin to assess the need for antibiotic treatment in patients with CAP presenting to the emergency department during the SARS-CoV-2 pandemic. Methods: We performed a real-world diagnostic retrospective accuracy study of procalcitonin in patients admitted to the emergency department. Measures of diagnostic accuracy were calculated based on procalcitonin results compared to the reference standard of combined microbiological and radiological analysis. Sensitivity, specificity, positive and negative predictive values, and area under (AUC) the receiver-operating characteristic (ROC) curve were calculated in two analyses: first assessing procalcitonin ability to differentiate microbiologically proven bacteria from viral CAP and then clinically diagnosed bacterial CAP from viral CAP. Results: When using a procalcitonin threshold of 0.5 ng/mL to identify bacterial etiology within patients with CAP, we observed sensitivity and specificity of 50% and 64.1%, and 43% and 82.6%, respectively, in the two analyses. The positive and negative predictive values of a procalcitonin threshold of 0.5 ng/mL to identify patients for whom antibiotics should be advised were 46.4% and 79.7%, and 48.9% and 79% in the two analyses, respectively. The AUC for the two analyses was 0.60 (95% confidence interval [CI] 0.52–0.68) and 0.62 (95% CI, 0.55–0.69). Conclusions: Procalcitonin measured upon admission during the SARS-CoV-2 pandemic should not guide antibiotic treatment in patients with CAP.

Evaluation of Procalcitonin's Utility to Predict Concomitant Bacterial Pneumonia in Critically Ill COVID-19 Patients.

Background: Historically, procalcitonin(PCT) has been used as a predictor of bacterial infection and to guide antibiotic therapy in hospitalized patients. The purpose of this study was to determine PCT's diagnostic utility in predicting secondary bacterial pneumonia in critically ill patients with severe COVID-19 pneumonia. Methods: A retrospective cohort study was conducted in COVID-19 adults admitted to the ICU between March 2020, and March 2021. All included patients had a PCT level within 72 h of presentation and serum creatinine of <1.5mg/dL. A PCT threshold of 0.5ng/mL was used to compare patients with high( ≥ 0.5ng/mL) versus low(< 0.5ng/mL) PCT. Bacterial pneumonia was defined by positive respiratory culture. A receiver operating characteristics (ROC) curve was utilized to evaluate PCT as a diagnostic test for bacterial pneumonia, with an area under the curve(AUC) threshold of 0.7 to signify an accurate diagnostic test. A multivariable model was constructed to identify variables associated with in-hospital mortality. Results: There were 165 patients included: 127 low PCT versus 38 high PCT. There was no significant difference in baseline characteristics, vital signs, severity of disease, or outcomes among low versus high PCT groups (all p > 0.05). While there was no difference in bacterial pneumonia in low versus high groups (34(26.8%) versus 12(31.6%), p = 0.562), more patients in the high PCT group had bacteremia (19(15%) versus 11(28.9%), p = 0.050). Sensitivity was 26.1% and specificity was 78.2% for PCT to predict bacterial pneumonia coinfection in ICU patients with COVID-19 pneumonia. ROC yielded an AUC 0.54 (p = 0.415). After adjusting for LDH>350U/L and creatinine in multivariable regression, PCT did not enhance performance of the regression model. Conclusions: PCT offers little to no predictive utility in diagnosing concomitant bacterial pneumonia in critically ill patients with COVID-19 nor in predicting increased severity of disease or worse outcomes including mortality.

Do biomarkers have predictive value in the treatment modality of the patients diagnosed with bowel obstruction?

This study aimed to investigate the ability of the biomarkers to predict the surgery treatment and mortality in patients above 18 years of age who were hospitalized with the diagnosis of bowel obstruction from the emergency department. This is a 2-year retrospective study. The patients' demographic data, laboratory parameters on admission to emergency department, treatment modalities, and the length of hospital stay were recorded. Patients were divided into two groups: conservative and surgical treatment. Statistical analysis was performed to investigate the value of biomarkers in predicting mortality and the need for surgery. Data were analyzed using IBM SPSS version 22. A total of 179 patients were included in this study. Of these, 105 (58.7%) patients were treated conservative and 74 (41.3%) were treated operatively. The elevated procalcitonin (PCT) level, C-reactive protein, blood urea nitrogen-to-albumin ratio, and lactate-to-albumin ratio were significantly correlated with surgical treatment, length of hospital stay, and mortality. procalcitonin threshold value of 0.13 ng/mL was able to predict the need for surgical treatment, with a sensitivity of 79% and a specificity of 70.3%. Procalcitonin threshold value of 0.65 ng/mL was able to predict the mortality rate of the patients, with a sensitivity of 92.9% and a specificity of 78.1%. Biomarkers, especially procalcitonin, may be useful in bowel obstruction treatment management and may predict mortality.

Utility of Procalcitonin as a Diagnostic Tool for Sepsis in Intensive Care Units

Introduction/Objective: Sepsis is one of the leading causes of mortality in the intensive care unit (ICU). Its diagnosis is often complex and represents a real clinical challenge. The objective of this study was to evaluate the usefulness of procalcitonin (PCT) as a diagnostic marker of sepsis. Methods: This prospective cohort study included 65 patients hospitalized in the ICU. Demographic and clinical data were collected according to a specific information sheet. All patients underwent an inflammatory assessment including PCT, hypersensitive C - reactive protein (hsCRP), and complete blood count. The Sequential Organ Failure Assessment (SOFA) score was calculated. Patients were classified into septic (SOFA ≥ 2 points) and non-septic (SOFA < 2 points). The Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic performance of inflammatory parameters. Results: Of 65 included patients, 46 had developed sepsis. Among the investigated inflammatory markers, PCT has the best discriminative capacity; its area under the curve (AUC), of 0.78, was the highest, followed by the neutrophils to lymphocytes ratio (NLR) and hsCRP with a lower but statically significant AUC. The optimal PCT threshold for sepsis diagnosis was 4.5ng/ml with a specificity of 83% and a sensitivity of 60%. A positive correlation between the PCT levels and the SOFA score was also found (p=0.002). Conclusion: This study provides additional evidence of the performance of PCT in the diagnosis of septic states in patients admitted to ICU. The newly established cut-off value provides the best balance between specificity and sensitivity. Its superiority over conventional inflammatory markers has been demonstrated.

Diagnostic Accuracy of Routinely Available Biomarkers to Predict Bacteremia in Children With Community-Acquired Pneumonia: A Secondary Analysis of the GPIP/ACTIV Pneumonia Study in France, 2009-2018.

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP.Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009–2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves.Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64–0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43–0.60]) and of ANC (0.55 [0.46–0.64]), but not than that of CRP (0.66 [0.56–0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively.Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Prognostic Value of Serum Procalcitonin Levels in Patients With Febrile Neutropenia Presenting to the Emergency Department.

Various risk-stratification scores have been developed to identify low-risk febrile neutropenia (FN). The Multinational Association of Supportive Care in Cancer (MASCC) score is a commonly used validated scoring system, although its performance varies due to its subjectivity. Biomarkers like procalcitonin (PCT) are being used in patients with FN to detect bacteremia and additional complications. Our objective was to compare the performance of MASCC score with PCT in predicting adverse outcomes in patients with FN. This was a prospective observational study that included chemotherapy-induced FN in hematologic or solid malignancy. The MASCC score, PCT levels, and blood cultures were taken at the first point of contact, and patient treatment was managed according to routine institutional protocol. The primary outcome was mortality at 30days. A total of 100 patients were recruited, of which 92 had hematologic malignancy and 8 had solid malignancy. Forty-six patients were classified as low risk by MASCC score (≥21). The PCT threshold, 1.42ng/mL, was taken as a cutoff value, with area under the receiver operating characteristic curve (AUROC) of 0.664 (95% confidence interval [CI] -0.55 to 0.77) for predicting mortality. AUROC for MASCC was 0.586 (95% CI 0.462 to 0.711). PCT is a useful marker with better prognostic efficacy than MASCC score in patients with FN and can be used as an adjunct to the score in risk-stratifying patients with FN.

Procalcitonin Level at 24 Hours of Age May be Predictive for Transient Tachypnea of the Newborn

Abstract Objective It is an important problem to differentiate transient tachypnea of the newborn (TTN) from bacterial pneumonia or other conditions in patients admitted to Neonatal Intensive Care Unit. The aim of this study was to evaluate the predictive value of procalcitonin (PCT) for TTN. Methods A total of 52 infants were contained in the study. The patients were divided into three groups. Group 1 consisted of patients with pronounced grunting at more than 2 hours postnatal age (n = 16). Group 2 consisted of patients whose grunt was reduced or gone at 2 hours postnatal age but in whom tachypnea persisted until 24 hours postnatal age (n = 18). Group 3 consisted of patients with minimal or no respiratory distress at 24 hours postnatal age (n = 18). In all groups, PCT concentrations were determined at birth and 24 hours postnatal age. Results PCT concentrations at birth were significantly higher in Group 1 than other groups, but there was no difference between Groups 2 and 3. PCT concentrations at 24 hours postnatal age were significantly higher in Groups 1 and 2 than Group 3. No difference was found between Group 1 and Group 2 at 24 hours postnatal age. All PCT concentrations in Group 3 were significantly lower than other groups. PCT thresholds for the diagnosis of TTN were 0.44 ng/mL at birth (sensitivity 58%, specificity 50%) and 5.11 ng/mL at 24 hours postnatal age (sensitivity 79.4%, specificity 89.1%). Conclusion Serial PCT measurements at birth and postnatal 24 hours may be helpful in differentiating between pneumonia and TTN. Further researches are needed to confirm this initial study.

Determination of the Optimal Procalcitonin Threshold for Infection in Patients With Impaired Renal Function at a Community Hospital.

Background: Procalcitonin (PCT) is a biomarker that can help identify bacterial infections but can be difficult to interpret in the presence of renal dysfunction, which can elevate PCT even in the absence of infection. Objective: To determine the optimal PCT threshold to identify infection in patients with renal dysfunction and pneumonia or sepsis. Methods: A retrospective analysis was performed for inpatients with creatinine clearance of ≤60 mL/min and PCT level from 2018 to 2019. A pharmacist blinded to study outcomes classified patients as infected or noninfected based on predetermined criteria. Receiver operating characteristic curve analysis was performed to establish the optimal PCT threshold overall, as well as in subgroups of patients with chronic kidney disease (CKD), acute kidney injury (AKI), and end-stage renal disease (ESRD). Institutional review board approval was obtained. Results: A total of 198 patients were included in the study (99 infected, 99 noninfected). The optimal threshold in the AKI, CKD, and ESRD subgroups was determined to be 1.5 ng/mL, 0.1 ng/mL, and 1.75 ng/mL, respectively. Conclusion: The results of this study show that PCT thresholds were specific to type of renal dysfunction. These results differ from the traditionally accepted PCT threshold of 0.5 ng/mL for sepsis and 0.25 mg/mL for pneumonia. Future studies should confirm the appropriate PCT threshold in ESRD and CKD patient populations.

Process analysis of procalcitonin monitoring within community hospitals.

Monitoring of procalcitonin (PCT) levels may support appropriate antibiotic discontinuation. The purpose of this study was to determine the current state of PCT monitoring at community hospitals across the United States. Data from adult patients who were admitted to community hospitals affiliated with a large healthcare system between August 1, 2016, and July 31, 2017, and who received antibiotics were evaluated for the number of PCT levels drawn and the timing between multiple levels. Data from eligible patients were evaluated for the discontinuation of antibiotics after meeting prespecified PCT thresholds for discontinuation of therapy, namely, a PCT measurement of <0.5 μg/L or a decrease of ≥80% from a previous peak value. PCT levels were evaluated for 103,913 patient data sets collected from 136 hospitals. Of these, 70% of the data sets showed a single PCT level drawn, and approximately 30% (30,887) of the data sets showed multiple levels drawn. The first PCT measurement was drawn within 36 hours of antibiotic initiation in 96% of the patients. Of those with multiple levels, 23% (7,089) had levels drawn 24 to 72 hours apart. A small proportion (20% [6,127]) of the patients with multiple levels were eligible for evaluation of appropriate antibiotic discontinuation. Of these, 1,973 (32.2%) patients had antibiotics discontinued within 36 hours of meeting the prespecified PCT thresholds; these patients had a mean duration of antibiotic therapy of 6.1 days with a median of 4.7. Additional standardization of ongoing PCT monitoring and education regarding the appropriate discontinuation of antibiotics when thresholds are reached could aid in the use of this biomarker in support of antibiotic and laboratory stewardship.

SUN-265 SERUM PROCALCITONIN LEVEL IN CHRONIC KIDNEY DISEASE STAGE 5 PATIENTS WHO ARE NON-DIALYSIS DEPENDENT AND ON MAINTENANCE DIALYSIS WITHOUT EVIDENCE OF INFECTION

Procalcitonin (PCT) is a 116-amino acid precursor protein of calcitonin,which is identified as a rapid and specific biomarker for diagnosing sepsis. The established PCT threshold in healthy individuals was <0.1ng/ml. A cut-off value for plasma PCT levels of ≥0.5ng/mL are interpreted as abnormal and suggest sepsis. There is large variability in baseline PCT has been observed in chronic kidney disease (CKD) stage 5 patients. The upper limit of serum PCT in CKD stage 5 patients who are non-dialysis dependent (NDD) and on maintenance dialysis for diagnosing sepsis is not well defined.

A semi-quantitative rapid multi-range gradient lateral flow immunoassay for procalcitonin.

A rapid semi-quantitative gradient lateral flow immunoassay (LFIA) of procalcitonin (PCT), a peptide precursor of the hormone calcitonin, was developed. The method is based on particular analyte cut-offs by immobilizing specific antibodies on the test strip with a consistent (gradient) increase in concentration from line to line. Semi-quantitative multi-range analysis is evaluated visually by counting the number of colored test lines corresponding to a certain concentration range of sepsis marker: [PCT]˂0.25; 0.25 ≤ [PCT] < 0.5; 0.5 ≤ [PCT] < 2; 2 ≤ [PCT] < 10; [PCT] ≥ 10ng·mL-1. This multi-range gradient LFIA was implemented by using two types of label: spherical gold nanoparticles (35nm) and hierarchical popcorn-like gold nanoparticles (100nm). The comparison of this LFIA with an ELISA (for n= 82) yielded 87.5% and 76.6% sensitivities, and 92.3% and 92.3% specificities, respectively. Thus, multi-range gradient LFIA performs well at PCT thresholds, which is important for early diagnosis of sepsis and severe bacterial infection. In our perception, this method has a wide scope in that it may be implemented in numerous other LFIA based test systems. Graphical abstract Schematic of the gradient lateral flow immunoassay for determination of clinically relevant procalcitonin ranges. It allows to reach the correlation between the number of developed test lines and procalcitonin concentration range in serum by pre-immobilization of capture antibodies in a consistently (gradient) increasing concentration.

2013. Procalcitonin Current State Evaluation Within a Large Health System

BackgroundProcalcitonin is a hormone precursor that has been identified as a marker for bacterial infections. Procalcitonin increases as the body mounts an inflammatory response against infection, then returns to its normal range once the response subsides. Studies have shown that reduced procalcitonin levels may support antibiotic discontinuation. The purpose of this study was to determine how procalcitonin is being utilized at facilities within a large health system.MethodsFrom August 1, 2016 through July 31, 2017 facilities with a minimum of 30 procalcitonin levels were assessed. Patients who received antibiotics, with and without procalcitonin levels, were evaluated. The primary outcome was the frequency of multiple procalcitonin levels drawn 24–72 hours apart. Secondary analysis included baseline procalcitonin timing, antibiotic discontinuation based on procalcitonin thresholds (<0.5 or 80% reduction from a peak level), and monitoring patterns related to outcomes such as hospital length of stay (LOS), intensive care unit LOS, antibiotic duration of therapy, and hospital-onset Clostridium difficile infections. Data were obtained from a centralized, enterprise data warehouse. The study was approved by the University of Tennessee Health Science Center Institutional Review Board.ResultsA total of 1,005,377 patients on antibiotics from 136 facilities were included. Procalcitonin levels were evaluated for 103,913 of these patients. Within the procalcitonin group, 96% had their first procalcitonin drawn within 36 hours of the first antibiotic dose and 70% of patients had a single procalcitonin level drawn. Of those with multiple levels, 23% had levels drawn 24–72 hours apart. Only 32% had antibiotic therapy discontinued within 36 hours of meeting threshold.ConclusionThere is wide variability among facilities regarding procalcitonin use and monitoring. Baseline procalcitonin levels were drawn appropriately for most patients. Opportunities exist to standardize monitoring and encourage discontinuation of antibiotics when thresholds are reached. The findings of this analysis will be used to aid efforts to establish a health-system wide procalcitonin monitoring protocol to support antibiotic and laboratory stewardship.Disclosures All authors: No reported disclosures.

Significance of serum procalcitonin for differentiating infections from rheumatic diseases

Differentiation between flare of a rheumatic disease (RD) and the development of infectious process is often extremely difficult due to the similarity of clinical and laboratory manifestations, as well as their lack of specificity.Objective of the study: to assess the significance of procalcitonin (PCT) test as a specific marker of generalized and local infection in patients with RD, and also to determine its role in assessing the inflammatory process activity in various RDs.Material and methods: The case records of 145 patients (101 women , 44 men, age of 3–79 years), who were undergoing inpatient examination and treatment at Nasonova Research Institute of Reumatology, were examined during the retrospective study. The serum PCT level was determined by the quantitative electrochemiluminescence method using the Cobas E 411 analyzer (Roshe, Switzerland).Results: The infectious process was diagnosed in 85 patients, the generalized one in 13 and the local one in 72. Local infections were divided into those with the light course – 41 and with the severe course – 31. In patients with generalized infection, the PCT level exceeded 2.0 ng/ml in 77% of cases and in 10.0 ng/ml in 46.2% of cases. Median (Me) PCT was 3.6 [2.26; 10.5] in the group with generalized infection. Me PKT exceeded the threshold values and amounted to 0.49 [0.19; 1.5] ng/ml in the case of a local infection with the severe course, PCT indices did not significantly differ from those of the group without infection (Me = 0.13 [0.08; 0.25] and 0.09 [0.06; 0.18 ] ng / ml, p&gt; 0.05).with a local infection of the lungs, The maximum values of PCT in the absence of infection and with a high activity of the rheumatic process were detected in patients with Adult-onset Still’s Disease (AOSD) – Me = 0.26 [0.10; 0.61] ng/ml, moderate increase was detected in patients with systemic-onset juvenile idiopathic arthritis (JIA)– Me = 0.2 [0.14, 0.24] ng/ml, juvenile rheumatoid arthritis (JRA) – Me = 0.2 [0.1; 0.26] ng/ml, systemic lupus erythematosus (SLE) – Me = 0.19 [0.11, 0.39] ng/ml.Conclusions: Determining PCT level undoubtedly contributes to the diagnosis of generalized infections, and differential diagnosis of systemic RD from the infectious process. Further research is required to determine the PCT threshold value for various RDs.

Association of Procalcitonin Value and Bacterial Coinfections in Pediatric Patients With Viral Lower Respiratory Tract Infections Admitted to the Pediatric Intensive Care Unit.

Our primary objective was to determine the utility of procalcitonin (PCT) in detection of bacterial coinfection in children < 5 years admitted to the pediatric intensive care unit with viral lower respiratory tract infection (LRTI). Electronic medical record review of children < 5 years admitted to the pediatric intensive care unit with a viral LRTI who also had at least 1 PCT concentration measurement. Seventy-five patients were admitted to the intensive care unit and met the inclusion criteria for this investigation. The PCT threshold concentrations of 0.9, 1, 1.4, and 2 ng/mL were found to be statistically significant in determining the presence of a bacterial coinfection. The PCT concentration with the most utility was 1.4 ng/mL with sensitivity, specificity, positive and negative predictive values of 46%, 83%, 68%, and 76%, respectively. For patients with serial PCTs, the second PCT correctly influenced treatment decisions for 11 of 25 patients (44%). A PCT value of 1.4 ng/mL determined the presence of a bacterial coinfection primarily owing to the high specificity and negative predictive value. Our data add evidence to the relatively high negative predictive value of PCT concentrations in identifying patients with bacterial coinfection, specifically in the case of viral LRTI. In addition, our preliminary data indicate serial PCT measurements may help further influence correct treatment decisions. Prospective, controlled studies are warranted to validate an appropriate PCT threshold concentration to help in identifying bacterial coinfection as well as to further explore the role of serial PCT values in determining the absence or presence of a bacterial coinfection.

Procalcitonin in liver dysfunction - Dr Jekyll or Mr Hyde?

Serum procalcitonin (PCT) is a sensitive biomarker used for the diagnosis of infection and sepsis. PCT has also some toxic effects. It is not a proinflammatory stimulus, but may augment the inflammatory processes. High levels of PCT in sepsis may lead to hepatocyte necrosis and, as a result, to liver failure. The pathomechanism of the toxic effect of PCT is still unknown. The influence of liver function on PCT levels has not been studied yet. It is not sure whether the liver dysfunction affects the diagnostic and prognostic value of serum PCT levels. In patients with acute liver failure, the usefulness of PCT-level determination remains controversial. Recent studies have shown a potential diagnostic benefit of PCT as a marker of infection in chronic liver diseases. In both groups there is still no consensus on the optimal cut-off value of PCT levels in order to exclude infection. In patients with liver disease, the serum PCT levels should be interpreted with caution, taking into consideration other factors affecting the PCT threshold.

Procalcitonin Monitoring as a Guide for Antimicrobial Therapy: A Review of Current Literature.

Effective antimicrobial stewardship practices are increasingly essential to best utilize the current arsenal of antimicrobials for the shortest necessary duration to minimize the development of antimicrobial resistance, secondary infections, and health care costs. Monitoring of serum procalcitonin (PCT) levels represents an effective antimicrobial stewardship strategy to differentiate bacterial infections from viral infections and noninfectious inflammatory conditions. Current literature illustrates the merits of PCT monitoring in reducing duration of antibiotic therapy without detrimental effects on mortality or infection relapses. However, the interpretation of PCT levels can be challenging, especially in light of comorbid disease states that can elevate PCT levels. This review sheds light on the utility of PCT monitoring, as well as providing insight into the practical interpretation of PCT levels. Much of the current literature surrounding PCT monitoring consists of use among patients with lower respiratory tract infections or in the critically ill. Overall, studies have demonstrated shorter antibiotic therapy durations when PCT monitoring is utilized. No studies to date have found increased rates of mortality or infection relapses, suggesting that PCT monitoring is not only effective, but also safe when used as a guide for antimicrobial therapy. Nonetheless, many conditions were shown to elevate PCT serum concentrations, even in the absence of bacterial infections, which can make interpretation of PCT concentrations challenging. Two common conditions that affect the accurate interpretation of PCT levels are renal dysfunction and congestive heart failure. Limited studies have been performed in these populations, but current available data propose the need for higher PCT thresholds in those with renal dysfunction or congestive heart failure and support utilizing PCT trends to monitor clinical improvement from bacterial infections. Evidence also suggests that PCT monitoring is cost-effective, as long as the test is ordered judiciously. In summary, PCT monitoring represents a promising antimicrobial stewardship strategy to limit exposure to unnecessary antimicrobial therapy.