Showing papers on "Procalcitonin published in 2001"

Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis

Abstract: To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.

Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis.

Abstract: Calcitonin precursors (CTpr), including procalcitonin, are important markers and also potentially harmful mediators in response to microbial infections. The source and function of CTpr production in sepsis, however, remains an enigma. In the classical view, the transcription of the CT-I gene is restricted to neuroendocrine cells, in particular the C cells of the thyroid. To better understand the pathophysiology of CTpr induction in sepsis, we used an animal model analog to human sepsis, in which bacterial infection is induced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr were elevated several fold in septic plasma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor-alpha and interleukin-6). Our findings, which describe a potentially new mechanism of host response to a microbial infection mediated by CTpr, introduce a new pathophysiological role for the CT-I gene.

Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children.

Abstract: Objectives: To evaluate procalcitonin (PCT) as a diagnostic marker of bacterial sepsis in critically ill neonates and children and to compare the results of PCT with those of C-reactive protein (CRP) and serum amyloid (SAA). Design and setting: Prospective, observational study in neonatal and pediatric intensive care units. Patients: A total of 116 divided into four groups according to age and diagnosis: neonates (aged 3–30 days) with sepsis (n=20), neonates without sepsis (n=26), children (aged 2–12 years) with sepsis (n=32), and children without sepsis (n=38). Interventions: Serum PCT, CRP, and SAA were measured on admission or when a bacterial sepsis was suspected. Area under the receiver operating characteristic (ROC) curve, optimum predictive values, and optimum diagnostic cut off values were evaluated. Results: Admission PCT was significantly higher in neonates and children with sepsis than in the other groups. In the neonates the area under the ROC curve was 0.99 for PCT, 0.95 for CRP, and 0.98 for SAA; in the children it was 1 for PCT, 0.93 for CRP, and 0.96 for SAA. Cutoff concentrations for optimum prediction of sepsis in the neonates were PCT >6.1 ng/ml (diagnostic efficiency: 93.8%), CRP >23.0 mg/l (89.7%), and SAA >41.3 mg/l (95.3%); in the children they were PCT>8.1 ng/ml (100%), CRP>22.1 mg/l (89.8%), and SAA>67.2 mg/l (94.4%). Conclusion: In critically ill children PCT concentration is a better diagnostic marker of sepsis than CRP and SAA. In critically ill neonates, however, PCT, CRP, and SAA are similar diagnostic markers of sepsis. A PCT concentration higher than 8.1 ng/ml identified all children with bacterial sepsis.

Procalcitonin in children admitted to hospital with community acquired pneumonia

Abstract: Aims—To assess the sensitivity, specificity, and predictive value of procalcitonin (PCT) in diVerentiating bacterial and viral causes of pneumonia. Methods—A total of 72 children with community acquired pneumonia were studied. Ten had positive blood culture for Streptococcus pneumoniae and 15 had bacterial pneumonia according to sputum analysis (S pneumoniae in 15, Haemophilus influenzae b in one). Ten patients had Mycoplasma pneumoniae infection and 37 were infected with viruses, eight of whom had viral infection plus bacterial coinfection. PCT concentration was compared to C reactive protein (CRP) concentration and leucocyte count, and, if samples were available, interleukin 6 (IL-6) concentration. Results—PCT concentration was greater than 2 µg/l in all 10 patients with blood culture positive for S pneumoniae ;i n eight of these, CRP concentration was above 60 mg/l. PCT concentration was greater than 1 µg/l in 86% of patients with bacterial infection (including Mycoplasma and bacterial superinfection of viral pneumonia).A CRP concentration of 20 mg/l had a similar sensitivity but a much lower specificity than PCT (40% v 86%) for discriminating between bacterial and viral causes of pneumonia. PCT concentration was significantly higher in cases of bacterial pneumonia with positive blood culture whereas CRP concentration was not. Specificity and sensitivity were lower for leucocyte count and IL-6 concentration. Conclusions—PCT concentration, with a threshold of 1 µg/l is more sensitive and specific and has greater positive and negative predictive values than CRP, IL-6, or white blood cell count for diVerentiating bacterial and viral causes of community pneumonia in untreated children admitted to hospital as emergency cases. (Arch Dis Child 2001;84:332‐336)

Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs.

Abstract: Fever without localising signs in very young children remains a diagnostic problem. Until present, a clinical scoring system combined with leucocyte count, urine analysis and determination of CRP are recognised as being helpful to identify patients at risk of serious bacterial illness. In this study we asked the question whether the determination of procalcitonin (PCT), interleukin (IL)-6, IL-8 and interleukin-1 receptor antagonist (IL-1Ra) was superior to these commonly used markers for the prediction of a serious bacterial infection (SBI). Children, 7 days to 36 months of age, with a rectal temperature above 38 °C and without localising signs of infection were prospectively enrolled. For each infant, we performed a physical examination, a clinical score according to McCarthy, a complete white cell count, an urine analysis and a determination of CRP. We further determined PCT, IL-6, IL-8, and IL-1Ra concentrations and compared their predictive value with those of the usual management of fever without localising signs. Each infant at risk of SBI had blood culture, urine and cerebrospinal fluid cultures when indicated, and received antibiotics until culture results were available. A total of 124 children were included of whom 28 (23%) had SBI. Concentrations of PCT, CRP and IL-6 were significantly higher in the group of children with SBI but IL-8 and IL-1Ra were comparable between both groups. PCT showed a sensitivity of 93% and a specificity of 78% for detection of SBI and CRP had a sensitivity of 89% and a specificity of 75%. Conclusion Compared to commonly used screening methods such as the McCarthy score, leucocyte count and other inflammatory markers such as interleukin-6, interleukin-8 and interleukin-1 receptor antagonist, procalcitonin and C-reactive protein offer a better sensitivity and specificity in predicting serious bacterial infection in children with fever without localising signs.

Procalcitonin as an acute phase marker.

Abstract: Procalcitonin is a 14-kDa protein encoded by the Calc-1 gene along with calcitonin and katacalcin. The function and regulation of this protein are quite different from those of the other gene products. Blood concentrations of procalcitonin are increased in systemic inflammation, especially when this is caused by bacterial infection. Studies of its behaviour in patients with bacterial sepsis have led to the proposal that it may be a useful marker of systemic bacterial infection, with greater specificity and sensitivity than acute phase proteins such as C-reactive protein.

Procalcitonin: how a hormone became a marker and mediator of sepsis.

Abstract: Calcitonin was discovered in the early 1960s [1], at which time it was assumed to be a single hormone with a yet-to-be-determined role in human physiology. Since then it has been found to be only one entity among a large array of related circulating peptides, at least one of which has a pivotal role in the host response to microbial infections [2, 3]. The aim of this review is to describe this metamorphosis of an endocrine hormone to a new class of hormokine mediators in infectious diseases.

The plasma elimination rate and urinary secretion of procalcitonin in patients with normal and impaired renal function

Abstract: Background and objective The amount of procalcitonin eliminated in the urine and the plasma disappearance rate of procalcitonin were evaluated in patients with normal and impaired renal function, because patients with sepsis are a main target group for procalcitonin measurement, and these patients often develop renal dysfunction.Methods Elimination of procalcitonin in the urine (μg 12 h−1) was measured in 76 patients. In another 67 patients, the 50% plasma disappearance rate (t½, h) was evaluated 48 h after peak concentrations (procalcitonin >2 μg L−1). Renal function was assessed by creatinine clearance.Results Procalcitonin elimination in the urine was significantly reduced in patients with severe renal dysfunction. However, the plasma disappearance rate correlated only weakly with renal dysfunction (Spearman's rank correlation R = −0.36, P = 0.004, regression t½ = 49.87−0.15 creatinine clearance). The 25% quartile and median were 25.2 h and 30.0 h in patients with normal renal function, and 36.3 h and 44.7 h in patients with severely impaired renal function (creatinine clearance <30 mL min−1).Conclusions Renal elimination of procalcitonin is not a major mechanism for procalcitonin removal from the plasma. Although the plasma disappearance rate may be prolonged up to 30–50% in some patients with renal dysfunction, clinical diagnostic decisions may not be severely influenced by this moderate prolongation of procalcitonin elimination. We conclude that procalcitonin can be used diagnostically in patients with renal failure as well as in those with normal renal function.

Usefulness of procalcitonin and C-reactive protein rapid tests for the management of children with urinary tract infection.

Abstract: Urinary tract infection (UTI) is a common problem in children. Because clinical findings and commonly used blood indices are nonspecific, the distinction between lower and upper urinary tract infection cannot be made easily in this population. However, this distinction is important because renal infection can induce parenchymal scarring. The objective of this study was to determine the accuracy of procalcitonin (PCT) compared with C-reactive protein (CRP) rapid tests to predict renal involvement in children with febrile UTI.

Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia

Abstract: The novel inflammatory marker procalcitonin (PCT) was assessed as an index of infection in patients with febrile neutropenia. Blood samples were obtained from 115 patients with febrile neutropenia for determination of PCT levels before onset of fever and daily until the resolution of fever. The median PCT level on the first day of fever was 8.23 ng/mL in patients with bacteremia, compared with 0.86 ng/mL in patients with localized bacterial infections (P=.017). The median PCT level on the first day of fever was 2.62 ng/mL in patients with severe sepsis, compared with 0.57 ng/mL in patients with clinically localized infections (P<.001). A dramatic decrease in PCT levels was documented after resolution of the infection; PCT levels were elevated when the infection worsened. Pronounced PCT levels were also found in patients with fever of unknown origin who were responding to antimicrobial chemotherapy, compared with those not responding to treatment with antibiotics. PCT levels were particularly elevated in patients with bacteremia and severe sepsis. These findings provide new insight into the application of PCT in clinical trials as a diagnostic tool of the severity of an infection in patients with febrile neutropenia and of the need to change antimicrobial regimen.

Procalcitonin and CGRP-1 mrna expression in various human tissues.

Abstract: Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.

Procalcitonin as a parameter of disease severity and risk of mortality in patients with Plasmodium falciparum malaria

Abstract: The serum levels of procalcitonin (PCT) in Plasmodium falciparum malaria were evaluated for clinical significance in 66 nonimmune and semi-immune patients. Of the 66 patients, 36 had uncomplicated malaria, 24 had severe and complicated malaria, and 6 had fatal malaria (5 from previous studies). Pretreatment PCT concentrations were closely correlated with parasitemia. Concentrations were lowest in semi-immune patients with uncomplicated malaria, compared with those in nonimmune patients (geometric mean concentrations [GMCs], 1.07 and 2.37 ng/mL, respectively), and were highest in severe and complicated cases (GMC, 10.67 ng/mL; P 25 ng/mL died. PCT concentrations decreased on day 2 of treatment in survivors but not in patients with fatal outcome. Thus, repeated PCT measurements may provide useful prognostic information, especially in medical centers that are not experienced in parasite density determination.

Usefulness of procalcitonin serum level for the diagnosis of bacteremia.

Abstract: The predictive value of procalcitonin serum levels to detect or rule out bacteremia was investigated prospectively in a case-control study with 200 hospitalized adults from whom blood samples were taken for culture. Fifty bacteremic patients (cases) had higher procalcitonin serum levels than the 150 controls with sterile blood cultures (11.7 vs. 0.7 ng/ml; P=0.0001), a difference that remained significant after controlling for potential confounders in multivariate analysis. At cut-off values of 0.5 and 0.2 ng/ml, the sensitivity of procalcitonin was 56 and 92%, and the specificity was 83 and 43%, respectively. These results yielded low positive (22 and 12%) and high negative predictive values (96 and 99%), reflecting primarily the low prevalence of bacteremia among patients who undergo blood cultures in hospitals (low pretest probability). Although caution is mandatory when using such markers at the individual level, procalcitonin, possibly together with other parameters, could nonetheless prove useful in future studies to rapidly rule out bacteremia.

Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients.

Abstract: Procalcitonin (PCT) has proven to be a very sensitive marker of sepsis for non-leucopenic patients. Little is known about its relevance in immunosuppressed and leucopenic adults. Four hundred and seventy-five PCT determinations were carried out in 73 haematological patients: on 221 occasions the white blood cell (WBC) count was 1.0 x 10(9)/l leucocytes. Patients were classified as: non-systemic infected controls (n = 280), patients with bacteraemia (n = 32), sepsis (n = 30), severe sepsis (n = 3), septic shock (n = 3) and systemic inflammatory response syndrome (SIRS) (n = 62). When the WBC count was > 1.0 x 10(9)/l, gram-negative bacteria induced higher PCT levels (median 9.4 ng/ml) than gram-positives (median 1.4 ng/ml). In cases with a WBC 2 ng/ml even in the sepsis and severe sepsis/septic shock groups, whereas a WBC count > 1.0 x 10(9)/l resulted in median PCT values of 4.1 ng/ml and 45 ng/ml respectively. The positive predictive value for sepsis (cut-off 2 ng/ml) was 93% in cases of WBC count > 1.0 x 10(9)/l, but only 66% in leucopenic conditions. The negative predictive value (cut-off 0.5 ng/ml) was 90% when the WBC count was > 1.0 x 10(9)/l and 63% in leucopenic conditions. Procalcitonin is an excellent sepsis marker with a high positive- and negative-predictive value in patients with WBC count > 1.0 x 10(9)/l, but it does not work satisfactorily below this leucocyte count.

Procalcitonin for accurate detection of infection in haemodialysis

Abstract: Background Infection results in considerable morbidity and mortality in haemodialysis patients. Diagnosis of infection can be difficult because currently applied laboratory parameters may be non-specifically altered due to uraemia or haemodialysis (HD). This study investigated the diagnostic value and kinetics of serum procalcitonin (PCT), a low-molecular-weight protein, in patients receiving intermittent HD. Methods Sixty-eight patients receiving intermittent HD for end-stage renal disease (n=48) or acute renal failure (n=20) were prospectively studied, 47 treated with high-flux and 21 with low-flux membranes. Of 36 patients with severe infections or sepsis, 27 were treated with high-flux and nine with low-flux membranes. WBC, serum PCT and C-reactive protein (CRP) concentrations were measured immediately before HD, and PCT repeatedly during the following 48 h. Results When determined immediately before HD, PCT demonstrated a sensitivity of 89%, a specificity of 81%, and positive and negative predictive values of 84 and 87%, indicating severe infection or sepsis. These levels were higher than the respective values for CRP (89, 48, 68 and 78%) and WBC (58, 75, 71 and 59%). After 4 h of HD with high-flux membranes, PCT decreased significantly to 83+/-25% and did not return to predialysis concentrations before 48 h. This decrease in serum PCT resulted in markedly reduced sensitivity (65%) and negative predictive value (54%). In contrast, no marked change in PCT concentration occurred during or after HD with low-flux membranes. Conclusion Serum PCT is an accurate indicator of severe infection and sepsis in patients receiving intermittent HD. High-flux membranes substantially decrease PCT. When utilizing high flux membranes, serum PCT concentrations should be determined prior to the start of HD.

Predictive value of serum and cerebrospinal fluid procalcitonin levels for the diagnosis of bacterial meningitis.

Abstract: Background: The value of serum and cerebrospinal fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis was assessed and compared to other parameters which are usually used in clinical practice. Patients: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study. Results: The median serum procalcitonin level in patients with bacterial meningitis was 6.45 ng/ml (range 0.25–43.76 ng/ml) and in the group with viral meningitis 0.27 ng/ml (range 0.05–0.44 ng/ml). 11 patients with bacterial meningitis had an elevated procalcitonin concentration not only in serum, but also in CSF. A serum procalcitonin level > 0.5 ng/ml had a positive predictive value for bacterial meningitis of 100% and a negative predictive value of 93%, while corresponding values for CSF procalcitonin were 100% and 74%, respectively. Conclusion: Serum and CSF procalcitonin concentrations > 0.5 ng/ml appear to be a reliable indicator of bacterial central nervous system (CNS) infection, with maximal positive predictive values and high negative predictive values.

Late Immunoneutralization of Procalcitonin Arrests the Progression of Lethal Porcine Sepsis

Abstract: Background: Procalcitonin (ProCT) is becoming increasingly recognized as a mediator as well as a marker of sepsis. Serum ProCT concentrations rise soon after induction of sepsis and remain elevated over a prolonged period of time. In contrast, many pro-inflammatory cytokines, e.g., tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), rise and decline early in the course of sepsis. Researchers have improved survival in animal models of sepsis by prophylactically blocking IL-1β and TNF-α with immunotherapy, but therapeutic treatment has been less successful in clinical trials. We hypothesized that the sustained elevation of ProCT in the serum would allow for effective therapeutic immunoneutralization of this peptide late in the course of sepsis. Methods: Lethal polymicrobial sepsis was induced in 10 castrated, male Yorkshire pigs by intraabdominal spillage of cecal contents (1 gm/kg) and intraabdominal instillation of 2 × 1011 cfu of a toxigenic strain of E. coli (O18:K1:H7). The treated grou...

Levels of three inflammation markers, C-reactive protein, serum amyloid A protein and procalcitonin, in the serum and cerebrospinal fluid of patients with meningitis.

Abstract: The levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) in blood are increased in patients with inflammatory diseases as acute phase proteins. Most of the presently used indicators of inflammation, such as body temperature, white cell count, erythrocyte sedimentation rate or CRP, are non-specific parameters. In contrast, procalcitonin (PCT) has been reported to be selectively induced by severe bacterial infection during the systemic inflammatory response syndrome (SIRS), and also in sepsis or multiorgan dysfunction syndrome. PCT expression is only slightly induced, if at all, by viral infections, autoimmune disorders, neoplastic diseases and trauma of surgical intervention. We measured the concentrations of CRP, SAA and PCT in the sera and cerebrospinal fluid (CSF) of 30 patients with bacterial, viral, or mycotic meningitis, and 12 patients with a noninflammatory central nervous system disease as controls. An extremely high CRP level in CSF of above 100 microg/L was seen in all seven bacterial meningitis patients and in only 10% of the viral meningitis patients. A high SAA level in CSF of greater than 10 microg/L was observed in all of the bacterial meningitis and mycotic meningitis patients, and in 95% of the viral meningitis patients. Among those with bacterial meningitis, the serum PCT level was more elevated in those with more serious bacterial meningitis. The PCT level in the CSF did not significantly differ among the patients with the three types of meningitis. However, the serum PCT level was very high above 0.1 microg/L in all seven bacterial meningitis patients, especially in the clinically serious cases.

Serum procalcitonin (PCT): a valuable biochemical parameter for the post-mortem diagnosis of sepsis.

Abstract: The aim of this prospective study was to investigate whether serum procalcitonin (PCT) can be used as a post-mortem marker of sepsis and to determine whether this biochemical parameter can be employed in the forensic elucidation of death due to sepsis. At least three blood samples were collected between 0.3 and 139 h post-mortem from sepsis-related fatalities (n = 8) and control individuals (n = 53, where death was due to various natural and unnatural causes). Additionally one ante-mortem blood sample was collected shortly before death from the patients in the sepsis group. In the sepsis group, serum PCT concentrations, determined by using an immunoluminometric assay, were elevated in all patients for the whole observation period, whereas in the control group serum PCT was not detectable in 94% of the cases. Measurement of PCT levels seems reasonable until at least approximately 140 h postmortem, depending on the ante-mortem levels. A linear regression model is presented that allows the serum PCT concentration of an individual at the time of death to be estimated on condition that at least two positive post-mortem PCT values have been determined. Ante-mortem PCT values correlated well with the predicted PCT values at the time of death in the sepsis group using the standardized PCT logarithms. According to the results of the present study, PCT is a valuable biochemical parameter for the post-mortem discrimination between sepsis and underlying non-septic causes of death.

Late immunoneutralization of procalcitonin arrests progression of lethal porcine sepsis

Abstract: BACKGROUND Procalcitonin (ProCT) is becoming increasingly recognized as a mediator as well as a marker of sepsis. Serum ProCT concentrations rise soon after induction of sepsis and remain elevated over a prolonged period of time. In contrast, many pro-inflammatory cytokines, e.g., tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), rise and decline early in the course of sepsis. Researchers have improved survival in animal models of sepsis by prophylactically blocking IL-1beta and TNF-alpha with immunotherapy, but therapeutic treatment has been less successful in clinical trials. We hypothesized that the sustained elevation of ProCT in the serum would allow for effective therapeutic immunoneutralization of this peptide late in the course of sepsis. METHODS Lethal polymicrobial sepsis was induced in 10 castrated, male Yorkshire pigs by intraabdominal spillage of cecal contents (1 gm/kg) and intraabdominal instillation of 2 x 10(11) cfu of a toxigenic strain of E. coli (O18:K1:H7). The treated group (n = 5) received an intravenous infusion of purified rabbit antiserum to the aminoterminus of porcine ProCT. The control group (n = 5) received nonreactive, purified rabbit IgG. The purified antiserum was infused to all animals 3 h after the induction of sepsis, at which time very severe physiologic dysfunction was manifest, and many of the animals appeared to be preterminal. Physiologic and metabolic parameters were measured until death or for 15 h after induction of sepsis, at which time all surviving animals were euthanized. RESULTS Therapeutic immunoneutralization of serum ProCT improved most measured physiologic and metabolic parameters in septic pigs. Specifically, there was a significant increase in mean arterial pressure, urine output and cardiac index in all animals treated with ProCT antibody. Serum creatinine was significantly lower in treated animals. Although acidosis was not as severe in treated animals, as indicated by higher pH values and lower lactate concentrations, these results did not achieve statistical significance. Significantly, 11 h after the induction of sepsis there was 100% mortality in the control group while only one animal in the treated group expired. CONCLUSION The prolonged elevation of ProCT concentrations in sepsis allows neutralization of this peptide to be effective during the course of this disorder. These findings suggest that immunoneutralization of ProCT may be a useful treatment in clinical situations where sepsis is already fully established.

Postnatal increase of procalcitonin in premature newborns is enhanced by chorioamnionitis and neonatal sepsis

Abstract: BACKGROUND To determine the influence of chorioamnionitis and neonatal sepsis on procalcitonin (PCT) levels in very-low-birth-weight (VLBW) infants within the first week of life. DESIGN PCT serum levels were measured in cord blood 1 h after delivery and on day 3 and day 7 of life. Chorioamnionitis and neonatal sepsis within the first week were monitored. RESULTS Chorioamnionitis was present in eight of 37 patients (21.6%). PCT on day 3 was increased in both the "No chorioamnionitis" (2.54 ng mL(-1), SEM 0.51) and "Chorioamnionitis" (6.96 ng mL(-1), SEM 2.93) groups of VLBW infants compared with the 1st hour values (0.45 and 0.58 ng mL(-1) SEM 0.07 and 0.11, respectively, P < 0.001) of the same patients. The postnatal gain was higher in the "Chorioamnionitis" group (P < 0.01). Neonatal sepsis was diagnosed (after exclusion) in 12 of 32 patients (37.5%). Mean values of maximum PCT in patients with and without sepsis were 8.41 ng mL(-1) (SEM 1.87) and 3.02 ng mL(-1) (SEM 1.38), respectively (P < 0.05). Sensitivity to sepsis of PCT, ratio of immature to total neutrophils (I : T), and C-reactive protein (CRP) were 75%, 50% and 25%, respectively. CONCLUSIONS In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. Compared with I : T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.

Serum procalcitonin in pneumococcal pneumonia in children

Abstract: Serum procalcitonin (PCT), a marker of bacterial infection, was measured in children with pneumonia to examine whether PCT can be used to screen pneumococcal (PNC) from viral pneumonia. The number of patients was 132; mean age 3.0 yrs, and 64% were males. In all cases, pneumonia was radiologically confirmed, being alveolar in 46 and interstitial in 86 cases. The aetiology of infection was studied by a panel of serological tests for PNC, for five other respiratory bacteria and for seven common respiratory viruses. PNC infection was found in 25, mixed viral-PNC infections in 13 and viral infection in 17 cases. In general, serum PCT was not associated with the type or aetiology of pneumonia. PCT values were >1.0 mg.L(-1) in 40% of PNC cases, as compared to 12-15% in viral or mixed cases, respectively (p 2 yrs old children than in younger ones. The cut-off limits of 0.5 ng.mL(-1), 1.0 ng.mL(-1) and 2.0 ng.mL(-1) were tested for screening between PNC and viral pneumonia. The highest sensitivity of 55% was found at the 0.5 ng.mL(-1) cut-off level, whereas the highest specificity of 88% was reached at the level of 1.0 ng.mL(-1). The likelihood ratios, however, were far from optimal for both the positive and negative results. Although marginally higher in pneumococcal pneumonia than in viral pneumonia, serum procalcitonin cannot be used to discriminate between these two types of pneumonia.

In vitro modulation of inducible nitric oxide synthase gene expression and nitric oxide synthesis by procalcitonin.

Abstract: ObjectiveSerum procalcitonin (PCT) concentration was recently introduced as valuable diagnostic marker for systemic bacterial infection and sepsis. At present, the cellular sources and biological properties of PCT are unclear. During sepsis and septic shock, inducible nitric oxide synthase (iNOS) ge

Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies

Abstract: Objective: To determine the value of procalcitonin (PCT) monitoring in transplant patients receiving pan-T-cell antibody therapy. Design: Retrospective clinical study. Setting: A collaborative study between the Institute of Medical Immunology, the Department of Nephrology and Internal Intensive Care, both Charite, Humboldt University Berlin, and the Department of Laboratory Medicine, Friedrichshain Hospital, Berlin, Germany. Patients and interventions: Thirty-one patients were included in the study: 8 kidney transplant patients with acute rejection episodes, 5 receiving OKT3 monoclonal antibody therapy, 3 receiving steroid bolus therapy; 21 patients undergoing renal transplantation, 11 receiving ATG perioperatively, 10 without ATG administration; 2 patients undergoing renal transplantation and receiving anti-IL-2R mAb. Measurements and results: Procalcitonin (PCT) and tumor necrosis factor (TNF) α plasma levels were measured in infection-free transplant patients treated with the pan-T-cell antibodies ATG or OKT3. We found PCT plasma concentrations up to 600 ng/ml (reference <0.5 ng/ml), which are comparable to those seen in severe sepsis. Increases in TNF-α plasma levels preceded the rises in PCT. After peaking on day 1 of therapy the PCT plasma concentrations returned to normal values independently of further antibody administration. In contrast, steroid bolus therapy or anti-interleukin 2 receptor mAb administration did not increase plasma PCT or TNF-α levels. Conclusions: PCT monitoring for evaluating infectious complications in kidney transplant patients must be very careful during pan-T-cell antibody therapy.

Serum procalcitonin measurement for detection of intercurrent infection in febrile patients with SLE

Abstract: It is sometimes difficult to distinguish infection from disease flare in febrile patients with systemic lupus erythematosus (SLE). Chill, leucocytosis, and increased C reactive protein (CRP) are known to be markers favouring infection.1 Procalcitonin (PCT) is the precursor of calcitonin and is synthesised in the parafollicular C cells of the thyroid. Serum PCT increases in severe bacterial or fungal infection but does not increase, or increases only slightly, in viral infections.2 3 The purpose of this study was to evaluate the usefulness of serum PCT in febrile episodes of patients with SLE to distinguish infection from disease flare. We prospectively enrolled 19 patients with SLE with fever who were admitted to Seoul National University Hospital between October 1998 and April 1999. Fever was defined as an axillary temperature over 38°C. Eleven patients with inactive SLE were enrolled as controls. Blood of the febrile lupus patients was withdrawn three times: on the day of the hospital visit, and after 24 hours and 48 hours. Another sample was withdrawn two weeks after defervescence to control infection or because of a decrease in lupus activity. At the detection of fever, blood cultures and other necessary cultures were performed with complete blood count, Westergren erythrocyte sedimentation rate (ESR), CRP, serum anti-dsDNA, complements …

Procalcitonin is not an accurate marker of spontaneous bacterial peritonitis in patients with cirrhosis.

Abstract: Background/Aims: The clinical features of peritonitis are usunlly absent in circhotic patients with an ascitic fluid infection, raising the interest for specific biological markers of inflammation. Methodology: We prospectively measured the plasma and ascitic fluid levels of procalcitonin, an innovative infection parameter, interleukin-6, and C-reactive protein in 20 cirrhotics with or without spontaneous bacterial peritonitis. The patient's condiction was followed-up for 12 weeks after paracentesis. Results: None of the 10 patients with spontaneous bacterial peritonitis presented with severe systemic signs of infection. Procalcitonin level in plasma, but not in ascites, was significantly higher in patients with spontaneous bacterial peritonitis compared to controls (0.74±0.6 vs. 0.2±0.1ng/mL. P<0.05). Interleukin-6 levels in ascites were similar between groups. C-reactive protein concentrations were higher both in plasma and in ascitic fluid in patients with spontaneous bacterial peritonitis compared to controls (85.3±68. vs. 18.6±19mg/dL, 24.6±25 vs. 4.5±4mg/dL, P<0.05, respectively). Three patients with spontaneous bacterial peritonitis died, but the outcome was not related to the concentrations of biological markers. Conclusions: In spontaneous bacterial peritonitis, procalcitonin measurement is not an accurate diagnostic test, possibly due to the absence of systemic inflammatory response syndrome in this condition. In addition, the diagnostic value of C-reactive protein In addition, the diagnostic value of C-reactive protein is limited by the wide overlap between values.

Procalcitonin, a donor-specific predictor of early graft failure-related mortality after heart transplantation

Abstract: Background To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mortality after HTx. Methods and Results PCT and C-reactive protein (CRP) serum concentrations were measured in samples collected immediately before pericardium opening from 81 consecutive brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2) were excluded from analysis. The remaining donors were retrospectively divided into 2 groups: donors for recipients who died within 30 days after HTx, after an early graft failure (group II, n=8), and all other donors (group I, n=71). No differences in donor and recipient demographic characteristics were found between groups. Areas under the receiver operating characteristic curves for graft failure...

Lipopolysaccharide-binding protein (LBP) and markers of acute-phase response in patients with multiple organ dysfunction syndrome (MODS) following open heart surgery.

Abstract: Cardiopulmonary bypass (CPB) is associated with an immunological injury that may cause pathophysiological alterations in the form of a systemic inflammatory response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS). Previous studies on this issue have reported different changes of immunological parameters during and after CPB, but there are no reports about the lipopolysaccharide-binding protein (LBP) in relationship to other markers of inflammation in patients with MODS following cardiovascular surgery. In the present study, we investigated the acute-phase response of patients with MODS of infectious and non-infectious origin following open-heart-surgery. Plasma levels of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP were measured in the first four postoperative days in 12 adult male patients with the signs of SIRS and two or more organ dysfunctions after myocardial revascularization (MODS-group), and 12 patients without organ insufficiencies (SIRS-group). There were no significant differences regarding age, weight, height, preoperative NYHA-classification, preoperative LVEDP, or the number of anastomosis. Patients with MODS had a significantly longer operation time, duration of ischemia, and duration of extracorporeal circulation. None of the patients in the SIRS group died, whereas in the MODS group, 4 patients died due to septic multiorgan failure. Plasma PCT and IL-6 concentrations were significantly elevated in all MODS patients. CRP and LBP showed no differences between the MODS and the SIRS group. Comparing the MODS patients with and without positive microbial findings, we found significantly elevated levels of PCT and LBP in those patients with documented infections. Our results indicate that LBP may be a new marker for the differentiation between a severe non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative course following CPB, while a microbiological result is still missing.

Low Sensitivity of Serum Procalcitonin in Bacterial Meningitis in Adults

Abstract: Several studies have suggested high predictive values of serum procalcitonin (PCT) for the discrimination of bacterial and viral meningitis in children and adults. Here, we report PCT serum concentrations in 12 adults suffering from bacterial meningitis. PCT on admission was normal ( < or = 500 pg/ml) in 3 and between 500 and 1,000 pg/ml in 2 patients without evidence of concurrent bacterial infections. Conversely, in 5 patients with PCT concentrations between 2,268 and 38,246 pg/ml other infections were present. PCT concentrations were higher with typical meningitis agents (pneumococci and meningococci 12,679 +/- 13,092 pg/ml vs. other bacteria 4048 +/- 9187 pg/ml, p = 0.041) whilst in nosocomial bacterial meningitis after neurosurgery (n = 3) serum PCT remained normal. We believe that PCT is of limited diagnostic value in adults suffering from bacterial meningitis, especially in cases due to unusual agents or of nosocomial origin. Elevated PCT in bacterial meningitis may indicate the presence of bacterial inflammation outside the central nervous system.