Cord blood levels of cytokines as predictors of early neonatal sepsis

AIM: To investigate whether cord blood levels of C-reactive protein, interleukin-1beta, interleukin-6, interleukin-8, tumour necrosis factor-alpha and the soluble receptor of interleukin-2, are useful markers in the diagnosis of early neonatal sepsis. DESIGN: Umbilical cord blood samples were obtained at birth from 261 neonates, but 5 of these newborns were excluded from the study. Group I included 10 newborns that developed early neonatal sepsis with a positive blood culture; Group II included 11 newborns with non-infectious perinatal diseases; Group III, which served as the control group, included 10 randomly selected patients, matched for gestational age, among the 235 healthy newborn babies. RESULTS: There were no differences among the three study groups in levels of C-reactive protein. interleukin-1beta, tumour necrosis factor-alpha and the soluble receptor of interleukin-2. Interleukin-6 was significantly elevated in Group I (360.4+/-157.8 pg/ml) and Group II (158.8+/-122.3 pg/ml), when compared with Group III (8.6+/-3.12 pg/ml) (p < 0.01), whereas interleukin-8 was significantly elevated in Group I (389.3+/-115.9 pg/ml) compared with Groups II (30.2+/-5.1 pg/ml) (p < 0.05) and III (33.9+/-8.6 pg/ml) (p < 0.05). A cut-off of 100.8 pg/ml for interleukin-6 obtained by the ROC (receiver operating characteristic) method gave a sensitivity of 50% and a specificity of 87%, and a cut-off of 111.7 pg/ml for interleukin-8 showed a sensitivity of 78% and a specificity of 91%. CONCLUSION: While cord blood levels of interleukin-6 appear to be related to pathological conditions in the perinatal period (infectious and non-infectious), interleukin-8 seems to be a good predictor of early bacterial neonatal infection.     

Clinical features of neonatal sepsis caused by resistant Gram-negative bacteria

Background:  Clinical features and outcomes of neonatal sepsis caused by resistant Gram-negative bacteria are not well described in Jordan. The aim of the present study was therefore to describe microbiology and clinical features, laboratory findings and outcomes of early- and late-onset Gram-negative neonatal sepsis.
Methods:  All patients with Gram-negative bacteremia between July 2003 and June 2005 were retrospectively included. Resistance profiles, clinical features and outcomes of early and late-onset neonatal sepsis were compared.
Results:  A total of 79 patients (after excluding all nine cases of Gram-positive bloodstream infection (BSI) were identified as having Gram-negative BSI (25 had early-onset and 54 had late-onset neonatal sepsis). Respiratory distress, metabolic acidosis and requirement of ventilation were found in 74.7%, 40.5%, and 58.2%, respectively. Hypotension was found in 22.9% of patients. Klebsiella pneumoniae was responsible for 43 cases (54.4.2%). Klebsiella pneumoniae resistance rates to ampicillin and ceftazidime were 100% and 50%, respectively. Mortality rate was 30.9%. Forty-eight percent of deaths occurred within 3 days of sepsis. Meningitis was diagnosed in five cases. Elevated C-reactive protein (CRP) and thrombocytopenia were seen in 28% and 24% of infants with early-onset sepsis, respectively, and in 79.6%, 59.3% of infants with late-onset sepsis respectively.
Conclusion:  Both early- and late-onset neonatal sepsis are caused by highly resistant Gram-negative bacteria. Mortality of sepsis is high. Elevated CRP and thrombocytopenia is seen more commonly in late-onset neonatal sepsis.     

Serum interleukin-1β in neonatal sepsis

Serum levels of interleukin-1β (IL-1β) in newborn infants with septicaemia were measured and possible relationships between the clinical course of the infants, causative micro-organisms and IL-1β levels were investigated in a prospective study. The study groups comprised 49 newborn infants (25 mature, 24 premature) with proven sepsis and 40 healthy newborn infants (20 mature, 20 premature). Serum IL-1β levels were measured using the IL-1β immunoradiometric assay. The levels were found to be lower in neonates with sepsis (median 0.1 pg/ml) than in healthy controls (median 27.9 pg/ml) ( p <0.001). Non-significant trends towards lower levels were observed in children with shock and in non-survivors. No correlation was found between IL-1β and postnatal age, gestational age or the study weight of the patients. There was no significant difference in the serum IL-1β level in septic patients infected with Gram-positive bacteria and those infected with Gram-negative bacteria. The results show that the concentration of IL-1β is significantly decreased in preterm and term neonates with sepsis.     

Serum TNF levels in neonatal sepsis and septic shock

Tumor necrosis factor (TNF-alpha) has been implicated as a principal mediator in the pathogenesis of septic shock. TNF-alpha was measured by immunoradiometric assay in serum samples from 23 full-term infants with sepsis (15 with severe infection and 8 with septic shock) and in 20 healthy full-term newborns. Serum TNF-alpha levels were significantly higher in the group with sepsis, at the time of admission to the neonatal intensive care unit, than in the healthy neonates. The highest TNF levels were found in those newborns with septic shock, particularly in those who died. Although the method is far too slow for any clinical routine work, our results suggest that the presence of elevated serum TNF-alpha levels could be considered a sensitive and specific test for predicting septic shock and its clinical outcome.     

Plasma cytokine levels in necrotizing enterocolitis

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.     

Serum fibronectin in neonatal sepsis: Is it valuable in early diagnosis and outcome prediction?

The value of the serum fibronectin level in early diagnosis of neonatal sepsis and as a prognostic indicator was investigated. The serum fibronectin levels and Töllner's sepsis scores of 45 neonates who were hospitalized for the suspicion of infection and of 20 healthy neonates as controls were evaluated. Depending on the findings it was concluded that serum fibronectin level varies according to the gestational age, and that the serum fibronectin level is a useful acute phase reactant in the early diagnosis of neonatal sepsis. It can also be used as a prognostic indicator in neonatal sepsis.     

Role of cytokines (interleukin-1beta, 6, 8, tumour necrosis factor-alpha,and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis

AIM: To investigate whether the serum levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha and the soluble receptor of IL-2 are useful in the diagnosis of neonatal sepsis, and whether their diagnostic power is increased when in combination with classical markers such as C-reactive protein and white blood cell count. METHODS: Blood samples were collected at admission from 40 neonates with suspected infection. Patients were included in different groups according to the bacteriological and laboratory results: Group I consisted of 20 newborns with positive blood cultures and other biological tests suggestive of infection. Group II included 20 neonates with negative blood cultures and biological tests not suggestive of infection. The control group included 20 healthy neonates with no clinical or biological data of infection. RESULTS: Mean values of C-reactive protein were significantly higher in Group I. No differences were found between the groups for white blood cell count, with the exception of the presence of leucocytosis in Group II. Levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha, soluble receptor of interleukin-2, and C-reactive protein were significantly higher in infected neonates than in the control groups. Detection sensitivity and specificity were 80 and 92% for C-reactive protein, 60 and 87% for interleukin-1beta, 61 and 80% for interleukin-6, 62 and 96% for interleukin-8, 54 and 92% for tumour necrosis factor-alpha and 63 and 94% for soluble receptor of interleukin-2. The discriminant analysis showed that the best combination for sepsis diagnosis was C-reactive protein + interleukin-8 + soluble receptor of interleukin-2, with a sensitivity of 85% and a specificity of 97.1%. CONCLUSION: Our study suggests that no individual test can on its own identify infected neonates, and that although the combination of C-reactive protein, interleukin-8 and the soluble receptor of interleukin-2 exhibits a high specificity, its sensitivity is limited.     

Role of routine lumbar puncture in neonatal sepsis

Objective: To evaluate the utility of lumbar puncture done routinely as part of complete workup in neonatal sepsis.
Methodology: Two hundred and nine consecutive lumbar punctures performed in 169 neonates were prospectively evaluated for the diagnosis of meningitis over a 6 month period in a tertiary care referral neonatal unit.
Results: Among babies with 'suspected clinical sepsis', five (3.3%) were diagnosed to have meningitis. None of the clinically normal babies with high risk obstetric factors alone had meningitis. The lumbar puncture was traumatic in 22.9%, and in 26.3% the fluid obtained was inadequate for complete analysis. The results were inconclusive in 37% of the cases.
Conclusion: Based on this study, routine lumbar puncture may not be required in clinically normal newborns with adverse obstetric factors. In babies with clinical sepsis, though the yield is not very high; there are no reliable clinical or laboratory markers to predict which babies will have meningitis and hence these babies would warrant a lumbar puncture.     

新生儿重症监护室晚发型败血症病原菌变迁及耐药性分析

目的 研究新生儿重症监护室(NICU)晚发型败血症(LOS)的病原菌分布、变迁及耐药情况。方法 回顾性分析2012年1月至2019年12月NICU收治的223例血培养阳性LOS新生儿的临床资料,分析病原菌逐年变迁特点。结果 223例新生儿中男116例、女107例,平均胎龄(31.9±1.2)周,平均出生体质量(1 584.1±620.9)g,发生LOS的中位年龄为19.0(13.0～27.0)d,早产儿203例、足月儿20例。共检出234株病原菌,以G^-菌检出最多(128株,54.7%),其中肺炎克雷伯杆菌77株;G⁺菌69株(29.5%);真菌37株(15.8%)。不同年份之间G^-菌、G⁺菌以及真菌检出率差异有统计学意义(P<0.01),G^-菌和真菌均以2016年检出率最高,G⁺菌以2014年检出率最高。G⁺菌、G^-菌及真菌组之间发病时间、剖宫产率、胎膜早破时间>18 h、抗生素暴露率及病死率差异均...     

Serum TNF-alpha and free radical scavengers in neonatal septicemia

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 ±605.8 pg/ml) as compared to those without shock (738.8 ±28.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.     

Utility of haematological parameters and C-reactive protein in the detection of neonatal sepsis

OBJECTIVE: To evaluate various haematological parameters, individually and in combination, to formulate a haematological scoring system (HSS, defined by Rodwell et al.), which can then be used to screen for sepsis in neonates who are clinically suspected of infection.1 METHODS: The study cohort consisted of 150 neonates (from birth to 3 days old) with clinically suspected infection. Blood was collected by peripheral venepuncture in all neonates. A complete blood count, differential leucocyte count, total leucocyte count (TLC), total neutrophil count (TNC), immature neutrophil count, band form count and platelet count were performed. Immature total neutrophil count (I/T) and immature/mature neutrophil count (I/M) ratios were then obtained. C-reactive protein (CRP) was measured semiquantitatively and blood culture and antibiotic sensitivity were performed in each case. The haematological parameters were compared individually and in combination (by HSS) with CRP. RESULTS: Twenty-one (14%) neonates had blood culture proven sepsis. On evaluation of various haematological parameters, TLC < 10 x 109/L, TNC < 8 x 109/L, I/M > 0.25, I/T > 0.14, band count > 15% and platelet count < 150 x 109 were found to have optimal sensitivities and negative predictive values (NPV). Using these values, an HSS was formulated. A haematological score > or = 3 had a sensitivity of 86% and NPV of 96%. C-reactive protein as a single test had a sensitivity of 76% and NPV of 96%. A combination of CRP with haematological parameters decreased the sensitivity and NPV of the HSS. CONCLUSIONS: A haematological score can be obtained by a complete blood count and examination of peripheral blood smear, thus permitting an objective assessment of haematological changes that occur in a neonate suspected of sepsis. C-reactive protein does not have any advantage over HSS, either as a single test or in combination.     

Feasibility and efficacy of gentamicin for treating neonatal sepsis in community-based settings: a systematic review

Background

Neonatal sepsis is a leading cause of neonatal deaths in developing countries. The current recommended in-hospital treatment is parenteral ampicillin (or penicillin) and gentamicin in young infants for 10- 14 days; however, very few could access and afford. The current review is to evaluate the feasibility of gentamicin in community based settings.

Methods

Both observational and randomized controlled trials were included. Medline, Embase, Cochrane Central Register of Controlled Trials and Central Trial Register of India were searched until September 2013. We assessed the risk of bias by Cochrane Collaboration’s "risk of bias" tool.

Results

Two observational studies indicated feasibility ensuring coverage of population, decrease in case fatality rate in the group treated by community health workers. In an RCT, no significant difference was observed in the treatment failure rates [odds ratio (OR)=0.88], and the mortality in the first and second week (OR=1.53; OR=2.24) between gentamicin and ceftriaxone groups. Within the gentamicin group, the combination of penicillin and gentamicin showed a lower rate of treatment failure (OR=0.44) and mortality at second week of life (OR=0.17) as compared to the combination of gentamicin and oral cotrimoxazole.

Conclusion

Gentamicin for the treatment of neonatal sepsis is both feasible and effective in community-based settings and can be used as an alternative to the hospitalbased care in resource compromised settings. But there was less evidence in the management of neonatal sepsis in hospitals as was seen in this review in which we included only one RCT and three observational studies.

     

脓毒症患儿血清可溶性CD14表达变化的临床研究

目的 探讨严重感染患儿血清脂多糖受体可溶性CD14(sCD14)的变化及其与脓毒症严重程度、预后的关系.方法 以32例脓毒症患儿为研究对象进行前瞻性临床研究.根据诊断标准及病情程度将脓毒症患儿分为3组,脓毒症组(10例)、严重脓毒症组(12例)、脓毒性休克组(10例).于发病后1 d、3 d、7 d测定血清sCD14的浓度,同时记录当天的血白细胞计数、前降钙素、C-反应蛋白、脂多糖以及危重病例评分.对照组为20例同期儿童保健门诊健康体检儿童.结果 脓毒症组发病1 d内血清sCD14水平为(8.09±4.33)mg/L,显著高于对照组(4.28±2.74)mg/L,差异有显著性(P<0.01).发病后3 d、7 d的sCD14水平与对照组差异无显著性(P>0.05).脓毒症组、严重脓毒症组、脓毒性休克组在病程1 d血清sCD14水平分别为(4.46±2.31)、(8.52±4.07)、(11.21±3.67)mg/L,差异有显著性(P<0.05).各组在病程3 d、7 d的血清sCD14水平差异无显著性(P>0.05).sCD14与前降钙素、C-反应蛋白、危重病例评分间存在显著相关(P<0.05).结论 在脓毒症早期sCD14的水平显著升高,其升高的程度可提示炎症反应的严重程度及预后.     

Maternal genital bacteria and surface colonization in early neonatal sepsis

Objective: The study was intended to evaluate the role of maternal genital bacteria and baby's surface colonization in early onset neonatal sepsis.Methods: Babies (born in the hospital of Jawaharlal Institute of Postgraduate Medical Education and Research) who developed clinical signs of sepsis were studied. Swabs were collected for culture from baby's umbilicus, ear, throat in addition to gastric aspirate and blood culture. The genital tract of the mother was also studied for bacterial colonization. The organisms isolated from the maternal genital tract and baby's surface colonization were correlated with those isolated from blood culture by calculating Phi correlation coefficient.Results:Esch coli was the most common organism isolated from maternal genital tract and surface cultures of babies, but Klebseilla-Spp was the most common organism isolated from blood. There was a significant correlation between surface colonization of babies and matermal genital bacteria, so also was baby's surface culture and blood culture. However, correlation between maternal genital bacteria and baby's blood culture was not significant.Conclusion: Surface colonizing bacteria and not maternal genital bacteria are important in early onset neonatal sepsis.     

Limitations of the risk factor based approach in early neonatal sepsis evaluations

Aim: Guidelines for detection of early neonatal sepsis employ a risk factor approach combined with laboratory parameters. In an era of increasing intrapartum antibiotic prophylaxis (IAP), we re-assessed the approach as a whole and each of the risk factors individually. Method: This retrospective study included infants with risk factors for sepsis or those treated with antibiotics or who had documented early sepsis. Safety of the protocol was assessed by the number of cases of either missed or partially treated late sepsis or meningitis and the sepsis-related mortality rate. Predictive value of each clinical and laboratory factor was calculated. Results: Of the 22 215 neonates, 2096 were assessed. IAP among infants with risk factors rose from 68% in 2005 to 78% in 2008 (p = 0.001). A total of 1662 asymptomatic infants had risk factors, 635 received antibiotics and one (0.06%) had sepsis. A total of 434 symptomatic infants were treated with antibiotics and of these 234 had risk factors and 20 (4.6%) had sepsis. No cases of partially treated or missed sepsis were detected. Poor predictive value was found for all risk factors except prematurity and leukopenia. Conclusion: The risk factor based approach in asymptomatic infants cannot be justified. In-hospital observation of asymptomatic infants for 2–3 days with antibiotic treatment being reserved only for symptomatic infants may be a reasonable alternative.     

Serum pro-hepcidin levels in term and preterm newborns with sepsis

Background:  An iron regulatory peptide hormone, hepcidin, is also part of the innate immune system and is strongly induced during infections and inflammation. The aim of the present study was to determine serum levels of the 60 aa pro-hormone form of hepcidin (pro-hepcidin) in full-term and preterm newborns with sepsis and to determine the possible relationships between pro-hepcidin levels and serum iron and complete blood count parameters.
Methods:  Fifteen preterm newborns with sepsis, 17 healthy preterm, six full-term newborns with sepsis and 16 healthy full-term newborns were included the study. Blood samples were collected from patients with sepsis at the time of clinical diagnosis. Each blood sample was analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and pro-hepcidin level.
Results:  The mean serum pro-hepcidin level (mean ± SD) in preterm neonates with sepsis and in healthy preterm newborns was 565.4 ± 519.5 ng/mL and 279.8 ± 227.6 ng/mL, respectively ( P <  0.05). The mean serum pro-hepcidin level in full-term newborns with sepsis and in healthy full-term neonates was 981.4 ± 415.4 ng/mL and 482 ± 371.9 ng/mL, respectively ( P <  0.05). Although the mean serum ferritin levels in the two groups with sepsis were higher when compared with the healthy groups, the difference was not statistically significant in full-term newborns. No statistically significant correlations were found between serum pro-hepcidin levels and any other parameters in each group.
Conclusions:  Serum pro-hepcidin levels were higher in newborns with sepsis (either premature or full-term) than they were in healthy newborns at the time of clinical diagnosis.     

Diagnostic value of plasma levels of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in newborns with sepsis

The aim of this study was to examine if TNFα and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and 11), a positive test result for plasma concentration of TNFα (> 70 pg/ml) had a sensitivity of 73 % and a specificity of 94%. A positive test result for IL-6 (>500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNFα and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio =α. The combination of TNFα and IL-6 determinations appears to be a good predictor of neonatal sepsis.     

Diagnosis of late onset neonatal sepsis with cytokines,adhesion molecule,and C-reactive protein in preterm very low birthweight infants

AIMS—To evaluate the commonly used markers—namely IL-6, TNFα, IL-1β, C-reactive protein and E-selectin for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment.METHODS—Very low birthweight infants in whom clinical sepsis was suspected when they were >72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined.RESULTS—One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNFα 17 pg/ml, IL-1β 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNFα on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection.CONCLUSIONS—Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNFα should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.