Low Procalcitonin Values Research Articles

Can serum procalcitonin be used for severity identification and guiding treatment of children admitted with community-acquired pneumonia? – A cross-sectional study

Background: Community-acquired pneumonia (CAP) remains one of the leading causes of mortality and morbidity in children under 5 years of age. Early diagnosis and effective management remain the cornerstone to reduce complications and fatalities associated with CAP. Lately, C-reactive protein (CRP) and procalcitonin (PCT) have gained much attention as useful biomarkers in CAP. Recent data suggest that a very low PCT value has a high negative predictive value while identifying a population of children at low risk of typical bacterial infections. Hence, we propose to take up this study to assess the clinical utility of PCT in pediatric CAP. Aims and Objectives: The aim of this study was to study serum PCT level in children with the clinical diagnosis of CAP admitted at R.G Kar Medical College and Hospital, Kolkata, and its role in severity identification and contribution in the treatment of CAP. Materials and Methods: This cross-sectional hospital-based observational study was performed from January 2020 to June 2021 in the R.G Kar Medical College and Hospital, Kolkata, West Bengal, India. A total of 50 children were included within the age group of 2 months–5 years with CAP admitted in the Children’s ward and intensive care unit at our hospital. Clinical characteristics such as age, sex, symptoms such as history of fever, difficulty feeding or drinking, convulsion, lethargy, cyanosis, chest in-drawing, respiratory rates, auscultatory findings such as air entry of bilateral lungs, added sounds like-(inspiratory crept, bronchial breathing), and oxygen saturation were studied. Routine investigations such as complete blood count, serum CRP, blood culture, and chest radiograph sent along with serum PCT. Results: Out of 50 children diagnosed with CAP, 30 (60%) fell within the age range of 2–5 months of age. Among the study population, 70% of children displayed weakly positive and 20% strongly positive serum PCT values. A strong correlation (P < 0.001) was revealed between the severity of pneumonia and PCT, and also a positive correlation (P < 0.001) between clinical outcome and PCT. However, the role in contribution in early diagnosis could not be concluded. Conclusion: This study concluded that serum PCT may be used as a valuable indicator for assessing the severity and prognosis of CAP. All children with elevated PCT who were prescribed antibiotics did not experience further complications of CAP.

C-reactive protein-guided use of procalcitonin in COVID-19.

BackgroundA low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein (CRP), can be concordant, and predicting low PCT concentrations may avoid costs of redundant tests and support more cost-effective deployment of this diagnostic biomarker.ObjectivesTo explore whether, in COVID-19, low PCT values could be predicted by the presence of low CRP concentrations.MethodsUnselected cohort of 224 COVID-19 patients admitted to hospital that underwent daily PCT and CRP measurements as standard care. Both 0.25 ng/mL and 0.5 ng/mL were used as cut-offs for positive PCT test results. Geometric mean was used to define high and low CRP values at each timepoint assessed.ResultsAdmission PCT was <0.25 ng/mL in 160/224 (71.4%), 0.25–0.5 ng/mL in 27 (12.0%) and >0.5 ng/mL in 37 (16.5%). Elevated PCT was associated with increased risk of death (P = 0.0004) and was more commonly associated with microbiological evidence of bacterial co-infection (P < 0.0001). For high CRP values, significant heterogeneity in PCT measurements was observed, with maximal positive predictive value of 50% even for a PCT cut-off of 0.25 ng/mL. In contrast, low CRP was strongly predictive of low PCT concentrations, particularly <0.5 ng/mL, with a negative predictive value of 97.6% at time of hospital admission and 100% 48 hours into hospital stay.ConclusionsCRP-guided PCT testing algorithms can reduce unnecessary PCT measurement and costs, supporting antimicrobial stewardship strategies in COVID-19.

Analytical Evaluation of the New Beckman Coulter Access Procalcitonin (PCT) Chemiluminescent Immunoassay.

This study was designed to evaluate the analytical performance of the recently commercialized Beckman Coulter Access procalcitonin (PCT) chemiluminescent test on the Access immunoassay system. The analytical assessment encompassed the estimation of limit of blank (LoB), limit of detection (LoD), functional sensitivity (i.e., PCT value with ≤10% imprecision), linearity, imprecision and comparability of values with BRAHMS PCT-sensitive Kryptor. LoB, LoD and functional sensitivity were 0.002 μg/L, 0.003 μg/L and 0.003 μg/L, respectively. Intra-assay, inter-assay and total imprecision for plasma pools with low, medium and high PCT values were 1.8–2.1%, 2.4–3.7% and 3.1–4.3%, respectively. The assay exhibited excellent linearity between 0.02 and 84.0 μg/L. Excellent correlation (r = 0.999; p < 0.001) and negligible bias (3.2%) were found by comparing values obtained in paired plasma samples with BRAHMS PCT-sensitive Kryptor. Diagnostic agreement at 0.5, 2.0 and 10 μg/L PCT values ranged between 98%-100%. The results of this study confirm that Access PCT displays excellent analytical performance and high comparability with BRAHMS PCT-sensitive Kryptor.

Introduction of Procalcitonin Testing and Antibiotic Utilization for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Background:The majority of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are triggered by nonbacterial causes, yet most patients receive antibiotics. Treatment guided by procalcitonin (PCT), a sensitive biomarker of bacterial infection, safely decreases antibiotic use in many controlled trials. We evaluated PCT implementation for inpatients with AECOPD at a large academic hospital.Methods:All patients admitted for AECOPD during the first 6 months of PCT-guided therapy were eligible for inclusion in this retrospective cohort study. Patients with PCT performed were compared with those without PCT. The primary outcome was antibiotic days of therapy (DOT). Secondary outcomes included 30-day readmission and mortality.Results:Of the 238 AECOPD admissions, 73 (31%) had PCT performed. Procalcitonin-tested patients were more likely to meet systemic inflammatory response syndrome (SIRS) criteria, require intensive care unit (ICU)-level care, and have a longer length of stay (LOS) compared with those without PCT. Even after adjustment for these factors, PCT-tested patients received more inpatient DOT and there was no difference in total DOT. However, a low PCT value (<0.25 ng/mL) was associated with a 25.5% (P ⩽ .001) decrease in intravenous (IV) antibiotic DOT. Guideline-recommended follow-up testing was rare (12%). Procalcitonin measurement had no effect on 30-day readmission or mortality.Conclusions:In this real-world analysis of inpatients with AECOPD, PCT-guided therapy was poorly adopted by providers and was not associated with a decrease in total antibiotic DOT. However, a low PCT level was associated with a 25.5% decrease in IV antibiotic DOT, suggesting increased comfort stepping down from IV to PO therapy.

Validation of the analytical performance of Lumipulse G BRAHMS procalcitonin immunoassay on low sample volume

Background: The measurement of procalcitonin (PCT) is currently considered a cornerstone in the diagnostic approach of patients with severe bacterial infections and for monitoring antimicrobial therapy. However, since low volume samples represent a challenge for PCT measurement, this study was aimed to investigate the analytical recovery of Lumipulse G BRAHMS PCT immunoassay using serially diluted lithium-heparin plasma samples. Methods: Fifteen fresh lithium-heparin plasma samples were arbitrarily selected to cover clinically significant measuring ranges of PCT values (low PCT, 0.034–0.085 ng/mL; medium PCT, 0.092–0.638 ng/mL; high PCT, 2.022–9.187 ng/mL). The samples were diluted with Lumipulse sample diluent, to obtain 5 progressive dilutions (1:2; 1:5; 1:10; 1:20 and 1:32). The original samples and each serial dilution were then measured with Lumipulse G BRAHMS PCT immunoassay, and PCT data obtained on dilutions were compared to their theoretical values. An additional measurement of original plasma samples was performed with automatic 1:10 sample dilution set in the analyzer. Results: The correlation between measured and theoretical PCT values was always excellent (i.e., r=0.999–1.000), whilst slopes and intercepts were also satisfactory. The mean recovery between theoretical and measured PCT values was ±14%, ±7% and ±1% for low, mean and high sets of samples, respectively. The mean recovery of 1:10 diluted specimens was comprised within ±20% with manual dilution and ±21% with automatic dilution for low PCT values, within ±5% with manual dilution and ±7% with automatic dilution for medium PCT values, within ±2% with manual dilution and ±1% with automatic dilution for high PCT values. Conclusions: The results of our study suggest that measuring PCT with Lumipulse G BRAHMS immunoassay using diluted (e.g., 1:10) plasma samples is a viable option to obtained accurate data and consume a much lower volume of plasma.

A Collaborative Approach to Improve Consistent Use of Procalcitonin in Lower Respiratory Tract Infections

Procalcitonin (PCT) is a biomarker that can help differentiate bacterial from viral infections and has been extensively studied in patients with sepsis and pneumonia to guide antibiotic therapy. However, there is poor adherence to prescribed algorithms when used to discontinue antibiotics in the real world. A quality improvement project was implemented to increase consistent use of PCT. To evaluate use of PCT and impact on antibiotic length of therapy (LOT) preimplementation and postimplementation of a quality improvement initiative. This was a single-center retrospective cohort study in patients with lower respiratory tract infections (LRTIs). In all, 330 patients were included in this study. Following implementation of the quality improvement initiative, ordering PCT in the first 24 hours increased from 59.6% to 75.5% ( P = 0.011). Documentation to discontinue antibiotics in patients with low initial PCT values increased from 13.2% to 28.6% ( P = 0.100). Increased PCT use correlated with an overall mean reduction of 1.05 antibiotic days between cohorts (6.82 ± 3.88 vs 5.77 ± 3.43, P = 0.028). There was no difference in incidence of antibiotic-associated adverse effects or 30-day hospital readmission rates attributed to pneumonia. Consistent use of PCT was achieved through a collaborative effort with the clinical pharmacy and hospitalist staff. Increased use of PCT was associated with a significant reduction in antibiotic LOT among patients with LRTIs. When controlling for other factors, low initial PCT values had the strongest influence on discontinuing antibiotics within 72 hours in the intervention group.

Procalcitonin for clinical decisions on influenza-like illness in emergency department during influenza a(H1N1)2009 pandemic

Purpose: We aimed to determine whether serum procalcitonin (PCT) values could help in identifying flu in patient admitted to the emergency department (ED) with influenza-like illness (ILI) during influenza A(H1N1)2009 pandemic.Methods: An observational retrospective cohort study was performed in a referral ED for emerging infectious diseases. All patients tested for influenza A(H1N1)2009 by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and procalcitonin between June 2009 and January 2010 were analyzed. PCT was studied for its negative predictive value of bacterial infection. Patients PCT−/RT-PCR + were considered as true positive.Results: On the 80 patients included, 16 were positive for influenza A(H1N1)2009 RT-PCR, all but one of them had low PCT concentrations. Conversely, 19 (30%) of the 64 patients with negative RT-PCR had elevated PCT concentrations. For a PCT threshold <0.25 μg/L, sensitivity was 0.94, specificity 0.30, positive predictive value 0.25 and negative predictive value 0.95 for the diagnosis of flu.Conclusion: In the context of an influenza pandemic, serum PCT measurement may be useful for clinical decisions in the ED as most of RT-PCR confirmed patients have low PCT values. Patients with PCT above 0.25 μg/L are unlikely to have a unique diagnosis of flu.

Does serum procalcitonin aid in the diagnosis of bloodstream infection regardless of whether patients exhibit the systemic inflammatory response syndrome?

Physicians frequently rely on the systemic inflammatory response syndrome (SIRS) criteria to detect bloodstream infections (BSIs). We evaluated the diagnostic performance of procalcitonin (PCT) in detecting BSI in patients with and without SIRS. We tested the association between BSI, serum PCT levels, contemporaneous SIRS scores and serum lactate using logistic regression in a dataset of 4279 patients. The diagnostic performance of these variables was assessed. In multivariate regression analysis, only log(PCT) was independently associated with BSI (p<0.05). The mean area under the curve (AUC) of PCT in detecting BSI (0.683; 95% CI 0.65-0.71) was significantly higher than serum lactate (0.615; 95% CI 0.58-0.64) and the SIRS score (0.562; 95% CI 0.53-0.58). The AUC of PCT did not differ significantly by SIRS status. PCT of less than 0.1ng/mL had a negative predictive value (NPV) of 97.4 and NPV of 96.2% for BSI in the SIRS-negative and SIRS-positive patients, respectively. A PCT of greater than 10ng/mL had a LR of 6.22 for BSI in SIRS-negative patients. The probability of BSI increased exponentially with rising PCT levels regardless of SIRS status. The performance of PCT for the diagnosis of BSI was not affected by SIRS status. Only PCT was independently associated with BSI, while the SIRS criterion and serum lactate were not. A low PCT value may be used to identify patients at a low risk for having BSI in both settings. An elevated PCT value even in a SIRS negative patient should prompt a careful search for BSI.

THE PROCALCITONIN TEST AS A NEARLY CRITERION TO DIAGNOSE SEVERE FORMS OF INTRAUTERINE INFECTIONS AND TO MONITOR ANTIBACTERIAL TREATMENT IN EARLY NEONATAL PERIOD

Background: Research in the field of reliable and available tests to diagnose infectious and inflammatory disorders in newborns in their first two days of life, as well as for determination of indications to antibacterial treatment and its monitoring in the early neonatal period are of utmost importance. Aim: To improve quality of diagnostics of intrauterine infections and to optimize management strategies for newborns with a high risk of infections by means of the procalcitonin test in the early neonatal period. Materials and methods: We assessed 40 normal (on-term) and 10 pre-term newborns born to mothers with infectious and inflammatory urogenital disease. Group 1 (n = 21) included patients with intrauterine pneumonia, group 2 (n = 6), those with intrauterine infection without a clearly defined primary locus, group 3 (n = 13), those with non-infectious disorders and group 4 (n = 10) comprised clinically normal (healthy) newborns. All infants underwent standard clinical and laboratory assessments, including an assessment of procalcitonin level by means of a semi-quantitative procalcitonin express-test (BRAHMS) at days 1, 2 and 3 of life. Results: At day 1, during primary assessment of newborns from group 1, procalcitonin values above 2 ng/mL were measured in 67% (10 of 15) cases; at days 2 and 3 also in 67% (4 of 6). Two patients with low procalcitonin values (below 0.5 ng/mL) had a disease of viral etiology (in 1, enteroviral and in 1, cytomegaloviral). In group 2, procalcitonin values exceeded 2 ng/mL in 3 of 5 newborns. In none of the infants from groups 3 and 4 procalcitonin values exceeded 2 ng/mL during their first 3 days of life. For assessment of efficacy of antibacterial treatment based on procalcitonin levels, all newborns with intrauterine infections were divided into group А (n = 11), where an antibacterial regimen was changed, and group B (n = 16), with no change in antibacterial treatment. During the treatment, 5 newborns from group A (45.5%) had their procalcitonin levels unchanged, whereas in 6 (54.5%) patients it decreased. In group B, 12 (75%) of newborns had their procalcitonin levels unchanged, in 2 (12.5%) it went down and in 2 (12.5%) of patients it went up. Conclusion: A semi-quantitative procalcitonin expresstest is characterized by its high informativity and availability when used in newborns of various gestation ages in the early neonatal period. An increase of procalcitonin level above 2 ng/mL, starting from the first day of life, can be used as an early diagnostic criterion of severe forms of intrauterine infections associated with systemic inflammatory response and symptoms of organ insufficiency. The results of procalcitonin test can be used for monitoring of antibacterial treatment in newborns.

Procalcitonin in pediatric intensive care unit of a tertiary care hospital

ObjectivesStudy was conducted to determine the role of procalcitonin (PCT) in the diagnosis of sepsis and guide antibiotic therapy in pediatric intensive care unit. MethodsPCT levels were measured from suspected sepsis patients along with a blood culture. ResultsOut of 52 patients, 30 had initial PCT levels ≥2.0ng/ml, 10 (≥0.5–<2.0ng/ml) and 12 (<0.5ng/ml). Initial PCT values were significantly higher in non-survivors as compared to that of survivors [15.3 (5.3–45.5) vs. 1.8 (0.33–8)ng/ml; P=0.006]. ConclusionsMeasurement of serum PCT levels was found to be helpful in diagnosing sepsis in culture negative patients. Lower PCT values can help in ruling out sepsis and limit antimicrobial use. High initial PCT levels can predict severity of sepsis and mortality.

Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial.

Background. Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital. Methods. Three hundred patients hospitalized with nonpneumonic LRTI during October 2013–April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months. Results. Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008–2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect. Conclusions. Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies. Clinical Trials Registration. NCT01907659.

1038

Introduction: The evidence for the clinical usefulness of procalcitonin (PCT) in adults with bacteremia has grown over the past two decades. In adults admitted with clinical signs of infection, low PCT values (<0.25μg/L) indicate a low probability for bacteremia, whereas elevated PCT values correlate with bacteremia (>1 μg/L) and septic shock (>10 μg/L). PCT guidance for initiation of antibiotics in adults is a growing trend. However, there is little evidence correlating PCT levels with bacteremia in the pediatric population. We examined PCT as a marker of bacteremia in children admitted to the pediatric intensive care unit with clinical signs of infection. Methods: We retrospectively reviewed all <10 yr old children admitted to the Riley Hospital PICU with suspicion of infection over a 6-month period. Only patients who had PCT levels, blood cultures (BCx), RSV assay, and respiratory cultures (RCx) obtained on admission were included. To assess the reliability of using PCT to predict bacteremia, we compared the incidence of bacteremia between those with PCT <1μg/L and those with PCT ≥1μg/L. We also assessed the effect of RSV pneumonia on PCT levels. Results: A total of 65 patients met inclusion criteria. The mean age was 17.6 months (range 0.7 to 45 mo). PCT was <1μg/L in 33 patients (mean 0.3μg/L, SD=0.2). Of these, 3 (9.1%) were bacteremic and 13 (39%) were RSV-positive. On the other hand, 32 patients had a PCT ≥1μg/L (mean 17.3μg/L, SD=8.3). Only 1 (3.1%) of these patients was bacteremic on admission. Sixteen (50%) were RSV-positive. The incidence of bacteremia (9.1 vs. 3.1%) between the two groups (<1 and ≥1μg/L respectively) was not statistically significant (p=0.613). When comparing only non-bacteremic patients, the mean PCT for RSV-negative patients (n=33) was 8.14μg/L (SD=15.11) whereas for RSV-positive (n=24) was 6.70μg/L (SD=12.12). The difference was not statistically significant (p=0.7). Conclusions: PCT levels are not a reliable indicator of bacteremia in children admitted to the PICU with clinical signs of infection. Infection with RSV raises PCT levels to near those typically seen with bacterial septic shock in adults.

Efficacy and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections.

Background: In 14 randomized controlled studies to date, a procalcitonin (PCT)-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs). However, compliance with the algorithm and safety out of controlled study conditions has not yet been sufficiently investigated. Methods: We performed a prospective international multicenter observational post-study surveillance of consecutive adults with community-acquired LRTI in 14 centers (Switzerland (n = 10), France (n = 3) and the United States (n = 1)). Results: Between September 2009 and November 2010, 1,759 patients were enrolled (median age 71; female sex 44.4%). 1,520 (86.4%) patients had a final diagnosis of LRTI (community-acquired pneumonia (CAP), 53.7%; acute exacerbation of chronic obstructive pulmonary disease (AECOPD), 17.1%; and acute bronchitis, 14.4%). Compliance with the PCT-guided therapy (overall 68.2%) was highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p < 0.001), outpatients (86.1% vs. inpatients, 65.9%; p < 0.001) and algorithm-experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001) and showed significant geographical differences. The initial decision about the antibiotic therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics were administered despite low PCT values but according to predefined criteria. Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox hazard ratio model, longer antibiotic therapy duration was associated with algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal failure and algorithm-naïvety of the study center. In a multivariable logistic regression complications (death, empyema, ICU treatment, mechanical ventilation, relapse, and antibiotic-associated side effects) were significantly associated with increasing CURB65-Score, CAP vs. bronchitis, multilobar pneumonia, but not with algorithm-compliance. Discussion: Cultural and geographic differences in antibiotic prescribing affected the compliance with our PCT-guided algorithm. Efforts to reinforce compliance are needed. Antibiotic stewardship with PCT is possible, effective and safe without increasing the risk of complications in real-life conditions.

1204 Utility of Serum Procalcitonin to Predict Renal Scars in Infant with Febrile Urinary Tract Infection

Background and AimsThe aim of this study was to evaluate the usefulness of Procalcitonin(PCT) as a marker for renal scars in infants with a first febrile urinary tract infection(UTI).DMSA scintigraphy,...

Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial

AimsBiomarkers have proven their ability in the evaluation of cardiopulmonary diseases. We investigated the utility of concentrations of the biomarker procalcitonin (PCT) alone and with clinical variables for the diagnosis of pneumonia in patients presenting to emergency departments (EDs) with a chief complaint of shortness of breath.Methods and resultsThe BACH trial was a prospective, international, study of 1641 patients presenting to EDs with dyspnoea. Blood samples were analysed for PCT and other biomarkers. Relevant clinical data were also captured. Patient outcomes were assessed at 90 days. The diagnosis of pneumonia was made using strictly validated guidelines. A model using PCT was more accurate [area under the curve (AUC) 72.3%] than any other individual clinical variable for the diagnosis of pneumonia in all patients, in those with obstructive lung disease, and in those with acute heart failure (AHF). Combining physician estimates of the probability of pneumonia with PCT values increased the accuracy to >86% for the diagnosis of pneumonia in all patients. Patients with a diagnosis of AHF and an elevated PCT concentration (>0.21 ng/mL) had a worse outcome if not treated with antibiotics (P = 0.046), while patients with low PCT values (<0.05 ng/mL) had a better outcome if they did not receive antibiotic therapy (P = 0.049).ConclusionProcalcitonin may aid in the diagnosis of pneumonia, particularly in cases with high diagnostic uncertainty. Importantly, PCT may aid in the decision to administer antibiotic therapy to patients presenting with AHF in which clinical uncertainty exists regarding a superimposed bacterial infection.Trial registration: NCT00537628

Reduction in antibiotic use through procalcitonin testing in patients in the medical admission unit or intensive care unit with suspicion of infection

We report an evaluation of the utility of serum procalcitonin (PCT) measurement as an additional diagnostic tool to support initiating or withholding antibiotics in clinical situations where there is a clinical suspicion of infection but the diagnosis is uncertain. During a six-month period, 99patients on the medical admission unit (MAU) with suspected infection, and 42patients on the intensive care unit (ICU) with clinical signs or physiological parameters suggesting possible new infection, had serum PCT concentration measured with the result available within 90min of the request. The test was initiated by the microbiology/infection team during clinical consultations to support the antibiotic decision. On the basis of low PCT values, antibiotics were withheld in MAU on 52occasions and in ICU on 42occasions. Patients were followed up prospectively for a week. There was neither progression of bacterial infection requiring antibiotics, nor complications or infection-related mortality in any patients who were denied antibiotics on either MAU or ICU. Without the PCT value it is likely that all of these patients would have received empirical antibiotics. Reduction in unnecessary antibiotic usage was made without any adverse effects on these patients and there was a clear reduction in antibiotic prescribing with cost reduction implications. PCT has the potential to become a valuable tool in antibiotic management.

37: Acute Heart Failure Patients Needing Antibiotic Therapy Can Be Identified by Procalcitonin Measurements: Observational Results From the BACH Multinational Trial

Procalcitonin (PCT) measurements have been used to diagnose bacterial infection and sepsis. Additionally PCT has been suggested as a surrogate marker reflecting the response to a clinically relevant bacterial infection requiring antibiotic treatment. However, PCT has never been used to identify possible bacterial infection co-morbidity in acute heart failure (AHF) patients. This observational study evaluates the association between PCT levels, patients who receive antibiotic therapy and all cause mortality within 90 days, the primary outcome of the BACH trial. The BACH trial was a prospective, 15-center multinational diagnostic and prognostic study of 1641 patients presenting to the ED with a primary complaint of dyspnea, 568 of which were diagnosed with AHF. Patients were included if they had a final diagnosis of AHF as the cause of their shortness of breath, determined by two cardiologists blinded to biomarker results and after reviewing all available clinical data 30 days after enrollment. Missing covariate data was imputed using the mean. PCT was significantly associated with all cause mortality within 90 days for patients diagnosed with AHF (p=0.0024, Cox regression). The proportion of antibiotic treatment during follow-up was significantly higher in patients with elevated PCT levels (p=0.0008, 2-fold increase). After adjusting for co-variates such as enrolling site, wheezing, history of stroke, creatinine level and neutrophil count to level out group differences, patients with a PCT level above 0.205 ng/ml (5th quintile of PCT in all AHF patients) had a significantly higher mortality if not treated with antibiotics (p=0.046). On the other hand, patients with very low PCT values (below 0.051 ng/ml, 1st quintile) had a significantly better 90-day survival if not treated with antibiotics (p=0.049). In all patients, as well as in patients with PCT levels between 0.051 and 0.205 ng/ml, the antibiotics treatment effect was not significant (p=0.58, p=0.36). These results suggest that in AHF patients, PCT may act as surrogate marker reflecting the response to a clinically relevant bacterial infection and the requirement for antibiotic treatment. Moreover, outcome results for patients with low PCT levels treated with antibiotics suggest that these individuals may be affected by adverse events from this therapy. As antibiotic therapy was not a randomized treatment in the BACH trial, these results need to be confirmed in a prospective randomized controlled trial.

Procalcitonin levels in surgical patients at risk of candidemia

Although the majority of cases of sepsis in intensive care unit (ICU) patients are due to bacterial infection, fungal infections are common and their early identification is important so that appropriate treatment can be started. Biomarkers have been used to aid diagnosis of bacterial infections, but their role in fungal infections is less defined. In this study we assessed the value of procalcitonin (PCT) levels for the diagnosis of candidemia or bacteremia in septic patients. We prospectively recorded PCT levels in 48 critically ill surgical patients with signs of sepsis and at high risk for fungal infection, and compared levels in patients with candidemia and bacteremia. Bacterial species were isolated from blood cultures in 16 patients, Candida species in 17, and mixed bacterial and Candida species in 2 patients. PCT levels were less elevated in patients with candidemia (median 0.71 [IQR 0.5-1.1]) than in those with bacteremia (12.9 [2.6-81.2]). A PCT value less than 2 ng/ml enabled bacteremia to be ruled out with a negative predictive value of 94%, and had a similar positive predictive value for candidemia. Our data indicate that a low PCT value in a critically ill septic patient is more likely to be related to candidemia than to bacteremia.

Biological Markers to Determine Eligibility in Trials for Community‐Acquired Pneumonia: A Focus on Procalcitonin

Clinical features such as cough, sputum production, fever, and the presence of a new lung infiltrate seen on radiograph are not specific to respiratory tract infection, nor do they define the need for antibiotic therapy. Therefore, investigators have looked for biological markers that can supplement clinical information to determine whether the etiology of the infection is more likely bacterial, needing antibiotic therapy, or viral. There are studies of a number of biological markers in serum and bronchoalveolar lavage fluid, including cytokines, acute-phase reactants, and immunoglobulins. The 2 most promising markers in serum are C-reactive protein and procalcitonin (PCT). PCT is a hormokine, produced primarily by parenchymal cells in response to microbial toxins and in response to certain host inflammatory mediators (interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6). Because PCT is down-regulated in the presence of viral infection, PCT seems most promising for defining the need for antibiotic therapy among patients with radiographic evidence of pneumonia. Studies using the highly sensitive Kryptor assay have shown that PCT guidance can lead to the safe withholding of antibiotics among patients with low PCT levels (<0.25 microg/L) and no clinical signs of severe illness. In addition, serial measurements of PCT have been reported to correlate with clinical response to therapy and may be able to guide short durations of therapy. In the future design of trials for community-acquired pneumonia, we may want to exclude patients with low PCT levels, because they are unlikely to benefit from antibiotic therapy. On the other hand, inclusion of patients with low PCT values creates heterogeneity in the study population and confounds the interpretation of clinical trial end points.

Low Levels of Procalcitonin During Episodes of Necrotizing Enterocolitis

The pathogenesis of necrotizing enterocolitis (NEC) remains poorly understood. We aimed to assess the extent of bacterial infection in the pathogenesis of NEC using serial procalcitonin measurements. Blood samples were drawn during the first 4 days following every clinical event requiring a workup for presumed NEC. Eight episodes were confirmed as NEC, 7 of which showed procalcitonin levels <1 ng/ml at presentation and <1.3 ng/ml thereafter, comparable to 24 healthy controls. The one infant with elevated procalcitonin had bacteremia in addition to NEC. Procalcitonin levels of 24 matched septic infants were higher than those of NEC infants, peaking at 4.1 ng/ml. We conclude that low procalcitonin values are the rule during episodes of NEC and provide further evidence that overactive local immune response, and not active infection, is primarily responsible for the mucosal damage in NEC.