calca-protein--human and Escherichia-coli-Infections

Recent news in the field of bloodstream infection and sepsis relevant for the practitioner include the recommendation in the newly revised German sepsis guideline to introduce selective intestinal decontamination with non-absorbable antimicrobial substances for the prevention of secondary infections in ventilated patients. This intervention, however, remains controversial because there are indications of unfavourable effects (increased development of resistance), and because the effect size has been rather low. Other news indicate not only that procalcitonin can be reasonably used as an aid to determine the duration of antibiotic treatment in community-acquired respiratory infection and pneumonia. A procalcitonin-based algorithm can also be used in critical care patients to shorten the duration of antibiotic administration without worsening outcomes. Recent data indicate that E. coli and S. aureus continue to be the most frequent pathogens isolated in bloodstream infection. The proportion of E. coli strains producing extended-spectrum beta lactamase (ESBL) is increasing. New epidemiologic evidence shows that infections with this pathogen, resistant to many standard antibiotics, are associated with an increased mortality rate, similar to infections due to methicillin-resistant Staphylococcus aureus (MSRA). The incidence of MRSA bacteraemia in Germany can now be estimated better as it has become a notifiable infection.

Topics: Algorithms; Anti-Bacterial Agents; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Care; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Germany; Humans; Methicillin-Resistant Staphylococcus aureus; Opportunistic Infections; Practice Guidelines as Topic; Protein Precursors; Sepsis; Splenectomy; Staphylococcal Infections

To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions.. In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later.. The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment.. Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Cefixime; Ceftriaxone; Child, Preschool; Drug Administration Schedule; Escherichia coli Infections; Female; Humans; Infant; Infusions, Intravenous; Male; Prospective Studies; Protein Precursors; Pyelonephritis; Radionuclide Imaging

To investigate the clinical features in adult patients with febrile urinary tract infection (UTI) who visited the emergency department (ED) and to determine the predictive factors of bacteremia among the initial presenting clinical features.. This retrospective cohort study was conducted at the ED of a tertiary hospital in Korea from 1 January 2012 to 31 December 2012. All adult patients who were diagnosed with febrile UTI and for whom data on blood and urine cultures were available were included in the study. Clinical examinations and laboratory tests were performed at the initial presentation.. A total of the 325 patients with febrile UTI (median age: 60 years) were included for analysis, of whom 82 % were female. Bacteremia was detected in 106 of the 325 patients (32.6 %), with Escherichia coli the most frequent pathogen detected (59.7 % of cases). Between the bacteremic and non-bacteremic groups, there was significant difference in age (67 vs. 57 years, respectively), flank pain (16 vs. 7.8 %), suprapubic discomfort (0 vs. 4.6 %), body temperature (38.8 vs. 38.3 °C), respiratory rate (21 vs. 20/min), platelet count (170 vs. 186 × 10(3)/μL), C-reactive protein (10.2 vs. 8.3 mg/dL), and procalcitonin (1.5 vs. 0.3 ng/mL) (P < 0.05 for all). In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.01-1.05], systolic blood pressure of <90 mmHg (OR 3.27; 95 % CI 1.13-9.45), body temperature of >39 °C (OR 4.26; 95 % CI 2.28-7.96), and procalcitonin level of >0.5 ng/dL (OR 2.03; 95 % CI 1.07-3.86) were significantly associated with bacteremia.. Among our adult patients with febrile UTI, age, systolic blood pressure, body temperature, and procalcitonin were significantly associated with bacteremia. We therefore suggest that these factors should be considered when deciding upon treatment options for febrile UTI patients at the ED.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Bacteremia; Blood Pressure; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Escherichia coli Infections; Female; Fever; Humans; Korea; Male; Middle Aged; Protein Precursors; Retrospective Studies; Temperature; Tertiary Care Centers; Urinary Tract Infections; Young Adult

Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB.. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls.. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis.. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

Topics: Adult; Asymptomatic Infections; Bacteriuria; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella; Klebsiella Infections; Pregnancy; Pregnancy Complications, Infectious; Protein Precursors; Proteus Infections; Proteus mirabilis

In this study we tested how a combination of early and late paraclinic markers could predict early onset neonatal sepsis (EONS).. The first 24 hours after the suspicion of EONS, we measured interleukine (IL)-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha (TNF-alpha), interferon gamma (INF-gamma), procalcitonin (PCT) and C-reactive protein (CRP) at 8-hour intervals on 123 neonates clinically suspected for EONS. The neonates were divided into two groups. The sepsis group: 1A with blood culture verified bacteraemia and 1B strongly suspected sepsis (29 patients). The no sepsis group: 2A treated with antibiotics (37 patients) and 2B not treated with antibiotics (57 patients).. Combined evaluation of each of the early markers with PCT > 25 ng/ml for prediction of EONS at time 0, gave the following sensitivities and specificities: IL-6 > 250 pg/ml: 71% and 88%; IL-8 > 900 pg/ml: 50% and 88%; IL-10 > 40 pg/ml: 43% and 87%; and immature/total (I/T) ratio > 0.35: 59% and 88%. The results of IL-18, TNF-alpha and IFN-gamma did not predict EONS.. IL-6 combined with PCT values is a fair way to evaluate EONS at the time of suspicion of infection. The "old" early marker, I/T ratio, is almost as efficient as IL-6. By combining an early and a late marker it may be possible to reduce the diagnostic "non-conclusive" period of paraclinic values.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Escherichia coli Infections; Female; Humans; Infant, Newborn; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Neutrophils; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis; Staphylococcal Infections; Streptococcal Infections; Streptococcus agalactiae; Tumor Necrosis Factor-alpha

Procalcitonin (PCT) and C-reactive protein (CRP) are two acute-phase reactants with different clinical features. The study aimed to compare the diagnostic value of admission serum PCT and CRP concentrations as indicators of aetiology and intensity of inflammation in children hospitalized with diarrhoea.. Serum PCT and CRP concentrations were determined on admission in 129 children hospitalized with diarrhoea. They were divided into four groups: group A: 37 children with diarrhoea as one of symptoms of ongoing systemic bacterial infection (sepsis/ meningitis): group B: 36 children with bacterial enterocolitis; group C: 43 children with rotaviral enterocolitis; and group D: 13 children with active inflammatory bowel disease (IBD). For comparison serum PCT and CRP concentrations were determined in 30 healthy controls.. PCT concentration was > 0.5 ng ml(-1) in all 37 (100%) children with diarrhoea and systemic bacterial infection (mean 18.5 +/- 3.2 ng ml(-1)) and CRP was above 2 mg dl(-1) in 33 (89%) of these children (11.7 +/- 1.5 mg dl(-1)). PCT concentration was > or = 0.5 ng ml(-1) in 22 of 36 (61%) children with bacterial enterocolitis (2.2 +/- 0.6 ng ml(-1)), in 3 of 43 (7%) children with rotaviral infection (0.2 +/- 0 ng ml(-1)) and in 3 of 13 (23%) patients with IBD (0.3 +/- 0.1 ng ml(-1)). CRP value was > or =2 mg dl(-1) in 22 (61%) children from group B (5.4 +/- 1.0 mg dl(-1)), in 8 (19%) children from group C (l.3 +/- 0.3 mg dl(-1)) and in 6 (46%) patients from group D (3.3 +/- 0.9 mg dl(-1)). In the control group the PCT (0.1 +/- 0.1 ng ml(-1)) and CRP (0.03 +/- 0.1 mg dl(-1)) levels were low or undetectable.. In this study PCT was a more reliable marker than CRP of systemic bacterial infection in children with diarrhoea. PCT was more specific but less sensitive in the differentiation of bacterial and non-bacterial aetiology of inflammation.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Diarrhea; Enterocolitis; Escherichia coli Infections; Female; Humans; Infant; Male; Neisseriaceae Infections; Protein Precursors; Rotavirus Infections; Staphylococcal Infections

To evaluate serum procalcitonin concentration in umbilical cord blood for diagnosis of intrauterine bacterial infection.. A prospective study was conducted between 2000 and 2001. Serum procalcitonin concentrations were evaluated in 187 umbilical cord blood samples. Five groups have been defined: controls A (n=37), full-term noninfected B1 (n=80) and infected neonates B2 (n=8), preterm noninfected C1 (n=38) and infected C2 (n=24) newborns. An immunoluminometric assay was used to determine procalcitonin concentration. The Mann-Whitney U-test and Spearman's correlation ratio were applied. The sensitivity and specificity, the positive and negative predictive values, and the area under receiver operating characteristic curves were calculated.. A statistically higher serum procalcitonin concentration was found in the preterm infected group (p<0.005; C2 vs A and C1).. Serum procalcitonin concentration in umbilical cord blood may be a useful parameter in the diagnosis of early neonatal infection.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Escherichia coli Infections; Fetal Blood; Fetal Diseases; Humans; Infant, Newborn; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Streptococcal Infections; Streptococcus agalactiae

The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model.. A prospective, controlled animal study.. A university research laboratory.. 30-kg Yorkshire pigs.. Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 x 10(11) colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit antiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified nonreactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs.. In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival.. These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

Topics: Animals; Antibodies; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Output; Escherichia coli Infections; Hydrogen-Ion Concentration; Immune Sera; Kidney; Lactic Acid; Prospective Studies; Protein Precursors; Rabbits; Sepsis; Swine

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin (PCT) levels and compared these with other commonly used inflammatory markers. We evaluated the ability of serum PCT levels to predict renal involvement, as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. Serum C-reactive protein (CRP), leukocyte counts, and PCT levels were measured in 64 children admitted for suspected UTI. Renal parenchymal involvement was assessed by (99m)Tc-DMSA scintigraphy in the first 7 days after admission. In acute pyelonephritis, the median PCT level was significantly higher than in the lower UTI group (3.41, range 0.36-12.4 microg/l vs. 0.13, range 0.02-2.15 microg/l, P<0.0001). In these two groups, respectively, median CRP levels were 120 (range 62-249 mg/l) and 74.5 (range 14.5-235 mg/l, P=0.012) and leukocyte counts were 15,910/mm(3) (range 10,200-26,900) and 14,600/mm(3) (range 8,190-26,470, P=0.34). For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT were 94.1% and 89.7%, respectively; CRP had a sensitivity of 100%, but a specificity of 18.5%. We conclude that serum PCT may be an accurate marker for early diagnosis of acute pyelonephritis.

Topics: Acute Disease; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Diagnosis, Differential; Escherichia coli Infections; Female; Humans; Infant; Infant, Newborn; Kidney; Leukocyte Count; Male; Prognosis; Prospective Studies; Protein Precursors; Pyelonephritis; Radionuclide Imaging; Sensitivity and Specificity; Succimer; Urinary Tract Infections

Procalcitonin (PCT) has been described as an early, discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, in part because no appropriate animal models have been available. We tested the hypothesis that plasma PCT increases during various pathophysiological conditions, such as hemorrhagic shock and sepsis, which differ with regard to the degree of associated endotoxemia. We further hypothesized that in sepsis, PCT would be significantly different in survivors vs. nonsurvivors.. Prospective, blinded analysis of previously collected plasma of experimental animals.. Independent nonprofit research laboratory in a trauma hospital and a contract research institute.. A total of 22 male baboons (17.5-31 kg).. Hemorrhagic-traumatic shock was induced by hemorrhage for up to 3 hrs, reperfusion with shed blood and infusion of cobra venom factor (n = 7). By using a similar experimental setup, severe hyperdynamic sepsis was induced (n = 15) by intravenous infusion of live Escherichia coli (2 x 10(9) colony-forming units/kg) over 2 hrs, followed by antibiotic therapy (gentamicin 4 mg/kg twice a day).. Plasma PCT at baseline was barely detectable, but levels increased significantly (p < .05) to 2+/-1.8 pg/mL 2 hrs after the start of reperfusion in the shock group, and to 987+/-230 pg/mL at 4 hrs after E. coli in the sepsis group. Levels were maximal between 6 and 32 hrs and had returned nearly to baseline levels at 72 hrs. Interleukin-6 levels paralleled the course of PCT measurements, whereas a significant increase in neopterin was seen at 24 hrs. PCT levels were approximately three times higher in the sepsis group than in the shock group, corresponding to endotoxin levels (at the end of hemorrhage, 286+/-144 pg/mL vs. 3576+/-979 pg/mL at the end of E. coli infusion; p = .003). PCT levels were significantly different at 24 hrs between survivors (2360+/-620 pg/mL) and nonsurvivors (4776+/-563 pg/mL) in the sepsis group (p = .032), as were interleukin-6 (1562+/-267 vs. 4903+/-608 pg/mL; p = .01) and neopterin/creatinine ratio (0.400+/-0.038 vs. 0.508+/-0.037; p = .032).. PCT is detectable in the baboon as in humans, both in hemorrhagic shock and sepsis. PCT levels are significantly higher in sepsis than in hemorrhage, a finding that is probably related to the differences in endotoxin. The baboon can be used for the study of PCT kinetics in both models; PCT kinetics are clearly different from other markers of sepsis, either IL-6 or neopterin, in both models. There are significant differences between survivors and nonsurvivors in the sepsis model.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Disease Models, Animal; Escherichia coli Infections; Interleukin-6; Male; Neopterin; Papio; Protein Precursors; Shock, Hemorrhagic; Shock, Septic; Survival Rate; Systemic Inflammatory Response Syndrome; Wounds and Injuries

Procalcitonin (ProCT), the precursor to the calcitonin hormone, is abnormally increased in experimental and clinical systemic inflammation, including sepsis. Initially, we investigated the effects of supraphysiologic amounts of ProCT administered to animals with septic peritonitis. Subsequently, we evaluated the efficacy of prophylactic and therapeutic immune blockade of ProCT in this lethal model of sepsis.. Prospective, experimental, controlled study.. Animal research laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at a Veterans Affairs Medical Center.. Young male Golden Syrian hamsters, weighing 90 to 120 g.. In the first study, serum ProCT concentrations were measured in animals at 0, 3, 6, 12, and 24 hrs after induction of sepsis by intraperitoneal implantation of pellets containing Escherichia coli (5 x 10(8) colony-forming units/pellet). In the second study, with mortality as the end point, 30 microg/kg of isolated, purified human ProCT in 10% hamster serum (experimental) or an equal volume of 10% hamster serum (control) were administered intravenously at the time of the E. coli peritoneal implantation. In the third study, experimental animals received intraperitoneal injections of a multiregion-specific goat antiserum reactive to hamster ProCT 1 hr before and 24 hrs after E. coli implantation, while control animals received nonimmune goat serum at the same time points. In the final study, the same antiserum was administered in five divided doses during the 24 hrs after the insertion of E. coli.. In the initial study, ProCT concentrations were increased shortly after induction of sepsis and peaked at 12 hrs. Administration of exogenous ProCT to septic animals significantly increased mortality compared with control animals (93% vs. 43%, p=.02). Prophylactic blockade of ProCT almost completely protected the animals from the lethal effects of sepsis: the 102-hr mortality rate in the experimental group was 6% compared with 62% in the control group (p < .003). In the therapeutic trial, the 102-hr mortality rate was 54% in experimental animals compared with 82% in control animals (p < .045).. These results demonstrate that increased ProCT exacerbates mortality in experimental sepsis, whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to being an important marker of severity of systemic inflammation and mortality, is an integral part of the inflammatory process and directly affects the outcome.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cricetinae; Escherichia coli Infections; Humans; Immune Sera; Immunization, Passive; Injections, Intraperitoneal; Male; Mesocricetus; Protein Precursors; Sepsis