Procalcitonin as a Marker of Serious Bacterial Infections in Febrile Children Younger Than 3 Years Old

Objectives There is no perfectly sensitive or specific test for identifying young, febrile infants and children with occult serious bacterial infections ( SBI s). Studies of procalcitonin ( PCT ), a 116‐amino‐acid precursor of the hormone calcitonin, have demonstrated its potential as an acute‐phase biomarker for SBI . The objective of this study was to compare performance of serum PCT with traditional screening tests for detecting SBI s in young febrile infants and children. Methods This was a prospective, multicenter study on a convenience sample from May 2004 to December 2005. The study was conducted in four emergency departments ( ED s): one pediatric ED and three ED s with pediatric units, all with academic faculty on staff. A total of 226 febrile children 36 months old or younger who presented to the four participating ED s and were evaluated for SBI by blood, urine, and/or cerebral spinal fluid ( CSF ) cultures were included. Results The test characteristics (with 95% confidence intervals [CIs]) of the white blood cell (WBC) counts including neutrophil and band counts were compared with PCT for identifying SBI. Thirty children had SBIs (13.3%, 95% CI = 8.85 to 17.70). Four (13.3%) had bacteremia (including one with meningitis), 18 (60.0%) had urinary tract infections (UTIs), and eight (26.6%) had pneumonia. Children with SBIs had higher WBC counts (18.6 × 10 9  ± 8.6 × 10 9 cells/L vs. 11.5 × 10 9  ± 5.3 × 10 9 cells/L, p < 0.001), higher absolute neutrophil counts (ANCs; 10.6 × 10 9  ± 6.7 × 10 9 cells/L vs. 5.6 × 10 9  ± 3.8 × 10 9 cells/L, p = 0.009), higher absolute band counts (0.90 × 10 9  ± 1.1 × 10 9 cells/L vs. 0.35 × 10 9  ± 0.6 × 10 9 cells/L, p = 0.009), and higher PCT levels (2.9 ± 5.6 ng/ mL vs. 0.4 ± 0.8 ng/ mL , p = 0.021) than those without SBIs. In a multivariable logistic regression analysis, the absolute band count and PCT were the two screening tests independently associated with SBI, although the area under the receiver operating characteristic (ROC) curve for PCT was the largest (0.80, 95% CI = 0.71 to 0.89). Conclusions Procalcitonin is a more accurate biomarker than traditional screening tests for identifying young febrile infants and children with serious SBI s. Further study on a larger cohort of young febrile children is required to definitively determine the benefit of PCT over traditional laboratory screening tests for SBI s. Resumen Objetivos No existe un test con la sensibilidad o especificidad ideal es para identificar las infecciones bacterianas graves ( IBG ) ocultas en los niños durante su primera infancia con fiebre. Los estudios de procalcitonina ( PCT ), un precursor de 116‐aminoácidos de la hormona calcitonina, han demostrado su potencial como biomarcador de fase aguda para las IBG . El objetivo de este estudio es comparar el rendimiento de la PCT en plasma con las pruebas de despistaje tradicionales para la detección de IBG en los niños durante la primera infancia con fiebre. Metodología Estudio prospectivo multicéntrico en una muestra de conveniencia realizado de mayo de 2004 a diciembre realizado de 2005. Este estudio se llevó a cabo en cuatro servicios de urgencias ( SU ): un SU pediátrico y tres SU con unidades pediátricas, todos ellos con docentes universitarios en la plantilla. Se incluyeron 226 niños de 0 a 36 meses de edad con fiebre que acudieron a los cuatro SU participantes y se les evaluó para IBG mediante cultivos de sangre, orina y/o líquido cefalorraquídeo. Resultados Los resultados (con los intervalos de confianza [IC] al 95%) del número de leucocitos, incluyendo número neutrófilos y blastos, y de la PCT se compararon para identificar las IBG. Treinta niños tuvieron IBG (13,3%, IC 95% = 8,85 a 17,70). Cuatro (13,3%) tuvieron bacteremia (incluyendo uno con meningitis), 18 (60,0%) infección del tracto urinario y 8 (26,6%) neumonía. Los niños con IBG tuvieron mayor número de leucocitos (18.600 ± 8.600 cel/mm 3 vs. 11.500 ± 5.300 cel/mm 3 , p< 0,001), número absoluto de neutrófilos (NAN) (10.600 ± 6.700 cel/mm 3 vs. 5.600 ± 3.800 cel/mm 3 , p = 0,009), número absoluto de blastos (900 ± 1.100 cel/mm 3 vs. 350 ± 600 cel/mm 3 , p = 0,009) y valores de PCT (2,9 ng/ mL  ± 5,6 ng/ mL vs. 0,4 ng/ mL  ± 0,8 ng/ mL , p = 0,021), que aquéllos sin IBG. En un análisis multivariable de regresión logística, el número absoluto de blastos y la PCT fueron los dos test de despistaje que se asociaron de forma independiente con IBG, aunque el área bajo la curva de rendimiento diagnóstico para la PCT fue la mayor de los test de despistaje (0,80, IC 95% = 0,71 a 0,89). Conclusiones La PCT es un biomarcador más preciso que las pruebas de despistaje tradicionales para identificar a los niños durante la primera infancia con IBG . Se requieren futuros estudios en una mayor cohorte de niños durante la primera infancia con fiebre para determinar de forma definitiva el beneficio de la PCT sobre las pruebas de despistaje de laboratorio tradicionales para identificar las IBG .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106122/1/acem12316.pd

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

Abstract\ud \ud \ud \ud Background\ud \ud Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile.\ud \ud \ud \ud Methods\ud \ud 52 adult patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at the onset of fever. The patients were divided into 2 groups, one with severe infection (n = 26) and the other in which the patients did not present such an infection (n = 26). Then PCT and CRP concentrations at the fever onset were compared between groups using non parametric statistical tests, ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient.\ud \ud \ud \ud Results\ud \ud The mean of PCT was significantly higher in the group with severe infection (6.7 ng/mL versus 0.6 ng/mL – p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of 2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any concentration of CRP.\ud \ud \ud \ud Conclusion\ud \ud PCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenic patients, probably better than CRP

Diagnostic accuracy of procalcitonin in critically ill immunocompromised patients

<p>Abstract</p> <p>Background</p> <p>Recognizing infection is crucial in immunocompromised patients with organ dysfunction. Our objective was to assess the diagnostic accuracy of procalcitonin (PCT) in critically ill immunocompromised patients.</p> <p>Methods</p> <p>This prospective, observational study included patients with suspected sepsis. Patients were classified into one of three diagnostic groups: no infection, bacterial sepsis, and nonbacterial sepsis.</p> <p>Results</p> <p>We included 119 patients with a median age of 54 years (interquartile range [IQR], 42-68 years). The general severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7) and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of immunodepression were hematological disorders (64 patients, 53.8%), HIV infection (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52 patients (43.7%) had no infection. PCT concentrations on the first ICU day were higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26] ng/ml in patients without bacterial infection, <it>P </it>< 0.0001). PCT concentrations on day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for diagnosing bacterial sepsis. The area under the receiver operating characteristic (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations > 0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95% confidence interval, 2.53-29.3; <it>P </it>= 0.0006). PCT concentrations were not significantly correlated with hospital mortality.</p> <p>Conclusion</p> <p>Despite limited specificity in critically ill immunocompromised patients, PCT concentrations may help to rule out bacterial infection.</p

Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.</p> <p>Methods</p> <p>We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.</p> <p>Results</p> <p>Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for <it>Pseudomonas aeruginosa</it>, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for <it>Haemophilus influenzae </it>had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, <it>P </it>= 0.80).</p> <p>Conclusion</p> <p>The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.</p

Pulmonary O-methyl transferases

An investigation in vitro of pulmonary O-methyl transferases revealed the presence of microsomal phenol-O-methyl transferase and soluble and microsomal catechol-O-methyl transferases in guineapig lung tissue. Both phenol and catechol transferases also were detected in rat and rabbit lung tissue. Substrates of guinea-pig pulmonary phenol-O-methyl transferase included phenols, cresols and xylenols. but not alcohols and amines. Catechol-O-methyl transferases from both subcellular sources were found to have similar pH optima, magnesium ion requirements, Km values, and utilized norepinephrine, isoproterenol and dopamine as substrates, but not metaproterenol and salbutamol. These data for the pulmonary enzymes are similar to published values for liver O-methyl transferases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22141/1/0000570.pd

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8