C-reactive protein as a marker of serious bacterial infections in hospitalized febrile infants

Objective:  To determine the potential predictive power of C-reactive protein (CRP) as a marker of serious bacterial infection (SBI) in hospitalized febrile infants aged ≤3 months.
Patients and Methods:  Data on blood CRP levels were collected prospectively on admission for all infants aged ≤3 months who were hospitalized for fever from 2005 to 2008. The patients were divided into two groups by the presence or absence of findings of SBI.
Results:  A total of 892 infants met the inclusion criteria, of whom 102 had a SBI. Mean CRP level was significantly higher in the infants who had a bacterial infection than in those who did not (5.3 ± 6.3 mg/dL vs. 1.3 ± 2.2 mg/dL, p < 0.001). The area under the ROC curve (AUC) was 0.74 (95% CI: 0.67–0.80) for CRP compared to 0.70 (95% CI: 0.64–0.76) for white blood cell (WBC) count. When analyses were limited to predicting bacteremia or meningitis only, the AUCs for CRP and WBC were 0.81 (95% CI: 0.66–0.96) and 0.63 (95% CI: 0.42–0.83), respectively.
Conclusion:  C-reactive protein is a valuable laboratory test in the assessment of febrile infants aged ≤3 months old and may serve as a better diagnostic marker of SBI than total WBC count.     

Procalcitonin and C-reactive protein levels in neonatal infections

In order to assess the potential of procalcitonin measurement in the management of neonatal sepsis, daily variations in serum procalcitonin (measured by an immunoluminometric assay) were evaluated in 94 control and infected newborn infants in comparison to C-reactive protein (measured by an immunonephelometric method). High levels of procalcitonin correlated with bacterial invasion and showed no discrepancies with C-reactive protein. Procalcitonin increased (up to 400 μg 1^-1) and returned to the normal range (< 0.1 g1^-1) more quickly than C-reactive protein, suggesting that procalcitonin may be an early marker of favourable outcome. Another finding is a significant procalcitonin peak on the first day of life in the control group, independent of any infectious stimulus. In conclusion, procalcitonin seems to be an interesting marker of neonatal sepsis but additional investigations are needed to understand better its mechanism of synthesis in order to determine its clinical usefulness.     

Influenza burden in febrile infants and young children in a pediatric emergency department

BACKGROUND: In France, epidemiologic data in children in ambulatory settings are scarce. We aimed to measure the burden of influenza in young children. METHODS: Febrile children younger than 36 months were consecutively recruited in a pediatric emergency department during the 2002 epidemic peak. Virology analysis and follow-up were systematic. RESULTS: During calendar weeks 3 to 6, 2002, 575 children were recruited; 49% were positive: A/H3N2 in 44% and B in 5%. Prevalence rate was 57% in 12- to 35-month-old children and 39% in infants younger than 12 months. The main clinical pictures were nonrespiratory in one third of them. One of 8 patients had a complication. One of 10 patients was hospitalized, and the estimated specific hospitalization rate for the study period was 237 of 100,000 in the general population among infants younger than 12 months. Forty-two percent of children (n = 110) were prescribed antibiotics and at least 34% of them were inappropriate (n = 89). Median length of disease was 8 days, and 25% of the children had not fully recovered by day 11. Only one child had been previously vaccinated of 65 with chronic conditions. Both epidemic strains were covered by the vaccine. CONCLUSIONS: Health outcomes showed that influenza disease burden in young French children is similar to that observed in North America. An active vaccination strategy would have strongly reduced the burden of influenza and lowered antibiotic use. Continuous efforts are needed to reach requirements of our influenza vaccination policy.     

降钙素原和C-反应蛋白对儿童全身和局部细菌感染的诊断价值

目的 探讨降钙素原（PCT）和C-反应蛋白（CRP）对诊断全身和局部细菌感染的价值。方法 检索2011年1月至2012年6月在深圳市儿童医院住院病史系统中感染性疾病患儿的资料,分为全身细菌感染组（血培养阳性的严重脓毒症和败血症）,局部细菌感染组（急性化脓性扁桃体炎、泌尿系感染及化脓性骨关节炎）,病毒感染组（传染性单核细胞增多症和手足口病）。比较各组PCT、CRP水平和阳性率的差异。绘制受试者工作曲线（ROC）,计算曲线下面积（AUC）,评估PCT和CRP对全身和局部细菌感染的诊断价值。结果 148例患儿进入分析,全身细菌感染组19例,局部细菌感染组55例,病毒感染组74例。①CRP水平(mg·L-1)、PCT水平(μg·L-1)和PCT阳性率局部细菌感染组低于全身细菌感染组（CRP：21.35 vs 76.0,P＝0.001;PCT:0.10 vs 28.09, 32.7% vs 100%,P均<0.001）;CRP水平和阳性率局部细菌感染组高于病毒感染组（21.35 vs 4.0, 73.1% vs 27.0%, P均<0.001), PCT水平和阳性率局部细菌感染组与病毒感染组差异无统计学意义。3组WBC计数差异无统计学意义;WBC阳性率全身细菌感染组高于病毒感染组（84.5% vs 54.0%,P=0.017）,局部细菌感染组与全身细菌感染组、病毒感染组差异无统计学意义。②PCT水平和阳性率局部细菌感染合并全身炎症反应综合征（SIRS）患儿显著高于不合并SIRS者（0.40 vs 0.08,P＝0.002;60.0% vs 17.1%, P＝0.001）,CRP水平和阳性率无显著差异。③PCT和CRP诊断全身细菌感染的ROC AUC分别为0.99和0.84;诊断局部细菌感染的ROC AUC分别为0.54和0.78。结论 PCT是识别全身细菌感染和监测局部细菌感染进展而合并SIRS的敏感指标。鉴别局部细菌感染时,CRP较PCT敏感。     

Serum C-reactive protein in early diagnosis of bacterial infections in premature infants

Serum C-reactive protein (CRP) is known to be produced by full-term infants and children in many diseases causing severe inflammation. We examined the usefulness of CRP as an early indicator of bacterial infection in premature newborn infants. CRP was obtained from 100 patients enrolled in a prospective study. All babies were suspected of having bacterial infection (meningitis-septicaemia) because of complications during pregnancy and/or symptoms suggestive of infection during the perinatal period. CRP was measured with the radial immunodiffusion technique. Examinations were done daily as long as elevated serum CRP levels were found. 100% (6/6) of our patients with culture-proven bacterial infections showed elevated CRP values within 24 h after the first clinical or laboratory signs suggesting sepsis. In 52.3% (11/21) of cases most probably suffering from infection, CRP rose within 72 h after the appearance of other symptoms. Even extremely immature infants were able to react with elevated CRP concentrations. Peak values of CRP were independent of birth weight. On the other hand, only 2.7% (2/73) of babies without findings of infection had slightly elevated amounts of CRP for a short time. Thus, serum CRP levels are a helpful parameter for the early diagnosis of severe bacterial infection in premature infants.     

Procalcitonin to detect invasive bacterial infection in non-toxic-appearing infants with fever without apparent source in the emergency department

The reliability of procalcitonin as a predictor of invasive infection in infants <36 months of age with fever and nontoxic appearance was assessed in 868 patients, 15 (1.7%) of whom had invasive infection. The area under the receiver operating characteristic curve for procalcitonin was 0.87 (optimum cutoff 0.9 ng/mL, sensitivity 86.7%, specificity 90.5%), whereas for C-reactive protein it was 0.79 (optimum cutoff 91 mg/L, sensitivity 33.3%, specificity 95.9%). In infants with fever of <8 hours duration, the area under the receiver operating characteristic curve was 0.97 for procalcitonin and 0.76 for C-reactive protein. Procalcitonin was a useful biomarker to predict invasive infection in non-toxic-appearing infants with fever without apparent focus, particularly in febrile episodes of <8 hours duration.     

Procalcitonin in comparison to C-reactive protein as markers of the course of sepsis in severely immunocompromised children after bone marrow transplantation

BACKGROUND: PCT has recently drawn attention as a quite specific marker for bacterial, fungal, and parasitic origin of severe sepsis-syndrome. These specific properties could make PCT to an important tool for sepsis monitoring in severely immunocompromised children. The clinical value of PCT in comparison to CrP was investigated in children after bone marrow transplantation (BMT). METHODS: PCT was measured in the serum of 48 children (median age 12.4 years) after BMT in a prospective study. Results were correlated with the clinical findings and compared to the C-reactive protein (CrP). RESULTS: PCT showed a sensitivity for diagnosing a sepsis-syndrome of 56%, a specificity of 87%, a positive predictive value of 69%, and a negative predictive value of 80%. Regarding CrP they were 100%, 41%, 46% and 100% respectively. The relative risk to die due to sepsis-syndrome was 26.4 for PCT levels over 10 ng/ml and 4.0 for CrP levels over 200 mg/l. It could be shown furthermore that there can be a significant liberation of PCT even during hematological aplasia. CONCLUSION: (1) Measuring PCT levels in the sera of children undergoing BMT improves the possibility of diagnosing severe infection and gives an important prognostic tool. (2) Measuring PCT can be recommended if severe sepsis-syndrome is suspected and there is an additional need for differential diagnosis and prognostic evaluation.     

C-reactive protein and bacterial infection in preterm infants

Serum C-reactive protein (CRP) concentration was measured by a new solid phase ligand-binding radiometric monoclonal antibody immunoassay in a prospective study of 193 consecutively born preterm infants. In 104 with no clinical or laboratory evidence of infection the median CRP in cord serum was 0.125 mg/l (range 0.011–6.0 mg/l), at 24 h it was 1 mg/l (0.016–7.0) and at 48 h 2 mg/l (0.400–8.0). The present highly sensitive assay has enabled these normal ranges to be defined for the first time, at levels below the threshold of non-labelled immunoassays and of all commercially available CRP assays. The values in cord serum were significantly lower than in normal healthy adults (median 0.8 mg/l, range 0.07–29 mg/l,n=468) [20]. Arterial catheterisation and endotracheal intubation, in the absence of infection, did not appear to elevate CRP, nor did cerebral germinal layer or intraventricular haemorrhage. Among nine infants with confirmed septicaemia eight had a serum CRP level raised at least once during the first 48 h and serum CRP in the other one increased 250-fold in 24 h before treatment was started. Using this assay, serum CRP is a useful and rapidly available adjunct to clinical assessment in diagnosis and exclusion of bacterial infection in the early neonatal period, has encouraged us to withhold or discontinue antibiotics and also has a role in monitoring response to treatment.     

Diagnostic values of C-reactive protein and complete blood cell to identify invasive bacterial infection in young febrile infants

Background

Newborn infants younger than 3 months old with a fever are frequently evaluated for the risk of invasive bacterial infections (IBIs), which include bacteremia and/or bacterial meningitis, in the pediatric emergency department (PED). The purpose of this study was to determine the individual complete blood cell count and biochemistry levels associated with IBIs in febrile infants.

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

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. Received: 29 May 2000 and in revised form: 15 September 2000 / Accepted: 25 September 2000