Diagnosis Of Late-onset Neonatal Sepsis Research Articles

Diagnostic Accuracy of Endotoxin and Endotoxin Binding Protein in Late-Onset Neonatal Sepsis.

To evaluate the diagnostic utility of endotoxin and endotoxin binding protein (EBP) for the diagnosis of late-onset neonatal sepsis (LOS) and compare it with the diagnostic utility of C-reactive protein (CRP). This diagnostic study of neonates, both term and preterm, with clinical suspicion of LOS was conducted in a tertiary care institute in India between January 2021 and March 2023. Blood samples were collected for evaluating endotoxin and EBP along with culture. Endotoxin and EBP were measured with enzyme linked immunosorbent assay, CRP was measured by nephelometry method, and the results were compared with blood culture done with BACTEC (gold standard). Out of 160 samples, 73 showed culture positivity. Endotoxin was positive in 81 samples and showed sensitivity of 84%, specificity of 78% and diagnostic accuracy of 81% (AUC 0.837, P value <0.001). EBP was positive in 82 samples and showed sensitivity of 80.8%, specificity of 73% and diagnostic accuracy of 76% (AUC 0.824, P value <0.001). CRP was positive in 105 samples and had sensitivity of 86%, specificity of 51% and diagnostic accuracy of 67% (AUC 0.827, P value <0.001). The present study showed endotoxin and EBP have higher specificity for diagnosing neonatal sepsis. As culture takes minimum 48h, endotoxin and EBP can be utilized as biomarkers for diagnosis of sepsis.

Evaluation of Changes in Leukocyte Surface Markers in the Early Diagnosis of Late-Onset Neonatal Sepsis

Abstract Objective This study aimed to evaluate the cluster of differentiation (CD)64, CD16, CD11b, CD63 human leukocyte antigen-DR (HLA-DR), and CD62L leukocyte surface marker abnormalities using flow cytometry in the early diagnosis of late-onset neonatal sepsis. Methods Forty-four neonates were included in this study. Of them, 22 neonates with clinical late-onset neonatal sepsis were included in the study group, and the remaining 22 neonates without sepsis were considered the control group. Complete sepsis screening was performed. Additionally, monocyte and neutrophil surfaces marker were examined using flow cytometry. Results The expression of the leukocyte surface markers CD16 and CD64 on monocytes and neutrophils was significantly higher in the study group than in the control group (p &lt; 0.05), while the CD63, CD62L, CD11b, and HLA-DR levels were similar to those in the control group (p &gt; 0.05). Furthermore, receiver operating characteristic curve analysis indicated that neutrophil CD64 (nCD64) is a diagnostic marker for neonatal sepsis, with an area under the curve of 0.901. The CD64 and CD16, which are the respective leukocyte surface markers on neutrophils and monocytes, are useful tests in the early diagnosis of late-onset neonatal sepsis. Conclusion In addition to acute phase proteins, cell surface antigens such as CD16 and more specifically CD64 should be used in routine investigations for the early diagnosis of late-onset neonatal sepsis. Such use in combination with acute phase reactants can improve diagnostic accuracy.

Early Diagnosis of Late-Onset Neonatal Sepsis Using a Sepsis Prediction Score

Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study (derivation cohort) we retrospectively reviewed the clinical files of 120 neonates with symptoms of suspected sepsis and identified clinical and laboratory parameters associated with proven sepsis on the day the blood culture was taken, as well as 24 h and 48 h earlier. These parameters were combined into a sepsis prediction score (SPS). Subsequently (validation study), we prospectively validated the performance of the SPS in a cohort of 145 neonates. The identified parameters were: temperature instability, platelet count < 150,000/mm3, feeding volume decrease > 20%, changes in blood glucose > 50%, CRP > 1 mg/dL, circulatory and respiratory deterioration. In the retrospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 82.54% sensitivity, 85.96% specificity, 5.88 PLR (Positive Likelihood Ratio), 0.20 NLR (Negative Likelihood Ratio), 86.67% PPV (Positive Predictive Value), 81.67% NPV (Negative Predictive Value) and 84.17% accuracy. In the prospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 76.60% sensitivity, 72.55% specificity, 2.79 PLR, 0.32 NLR, 83.72% PPV, 62.71% NPV and 75.17% accuracy. We concluded that this combination of clinical and laboratory parameters may assist in the prediction of septicemia in NICUs.

Monitoring of heart rate characteristics to detect neonatal sepsis.

Monitoring of heart rate characteristics (HRC) index may improve outcomes of late-onset neonatal sepsis (LOS) through early detection. We aimed at describing the association between LOS and elevated HRC index. This single-center retrospective case-control study included neonates who presented with blood culture-proven hospital-acquired LOS. Controls were matched to cases (ratio 1:2) based on gestational age, postnatal age, and birthweight. We compared the highest HRC indexes in the 48 h preceding blood culture sampling in LOS cases to the highest HRC indexes at the same postnatal days in controls. In 59 LOS cases and 123 controls, an HRC index > 2 was associated with LOS (OR 7.1, 95% CI 2.6-19.0). Sensitivity and specificity of an HRC index > 2 to predict LOS were 53% (32/59) and 79% (98/123). Sensitivity increased from 25% in infants born > 32 weeks to 76% in infants born < 28 weeks. Specificity decreased from 97% in infants > 32 weeks to 63% in those born < 28 weeks. An increase of HRC index > 2 has a significant association with the diagnosis of LOS, supporting the use of HRC monitoring to assist early detection of LOS. Clinicians using HRC monitoring should be aware of its diagnostic accuracy and limitations in different gestational age groups. There is a paucity of data regarding the predictive value of heart rate characteristics (HRC) monitoring for early diagnosis of late-onset neonatal sepsis (LOS) in daily clinical practice. Monitoring of heart rate characteristics provides valuable information to assist the early diagnosis of LOS across all gestational age groups. However, the strong influence of gestational age on positive and negative predictive values adds complexity to the interpretation of HRC indexes.

Salivary and Serum Interleukin-10, C-Reactive Protein, Mean Platelet Volume, and CRP/MPV Ratio in the Diagnosis of Late-Onset Neonatal Sepsis in Full-Term Neonates.

Salivary markers could serve as potential noninvasive markers in the diagnosis of neonatal infections. We aimed to investigate the diagnostic role of salivary and serum interleukin 10 (IL-10), C-reactive protein (CRP), mean platelet volume (MPV), and CRP/MPV ratio in the diagnosis of late-onset neonatal sepsis in full-term neonates. Seventy full-term neonates were enrolled in this prospective case-control study, 35 with late-onset neonatal sepsis, and 35 controls. Salivary IL-10, serum IL-10, and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Complete blood (CBC) count was measured by an automated blood cell counter. The salivary IL-10, serum IL-10, CRP, MPV, and CRP/MPV ratio levels were much higher in neonates with late-onset sepsis than in control (220 ± 150 vs. 18 ± 9 pg/ml, P < 0.001), (316 ± 198 vs. 23.7 ± 14 pg/ml, P < 0.001), (78.2 ± 34 vs. 3.3 ± 1.7 mg/L, P < 0.001), (11.2 ± 0.9 vs. 8.6 ± 0.4 fL), and (7.08 ± 3.3 vs. 0.4 ± 0.2, P < 0.001), respectively. At the cutoff point of >31 pg/ml, salivary IL-10 showed 97.1% sensitivity and 94.3% specificity. Serum IL-10 at a cutoff value of ≥33.6 pg/ml had a sensitivity of 97.1% and specificity of 80%. MPV showed a sensitivity of 100% and specificity of 94.4% at a cutoff value ≥ 9.2 fL. CRP/MPV ratio showed a sensitivity of 100% and specificity of 97.1% at a cutoff value > 0.9. Salivary and serum IL-10 showed a positive correlation with CRP and CRP/MPV ratio in septic neonates. The current study shows for the first time that both salivary IL-10 and CRP/MPV showed statistically significant differences between neonates with late-onset sepsis and controls. Accordingly, salivary IL-10 could serve as a potential noninvasive biomarker for the diagnosis of late-onset sepsis in full-term neonates.

Evaluation of serum and salivary C-reactive protein for diagnosis of late-onset neonatal sepsis: A single center cross-sectional study

ObjectiveTo evaluate the diagnostic utility of salivary C-reactive protein (CRP) and its potential correlation with serum CRP levels in full-term neonates with late-onset sepsis (LOS). MethodsThis cross-sectional study included 90 neonates assigned to three equal groups: culture proven LOS, clinical LOS and a control group. Clinical findings and routine laboratory data including complete blood pictures and blood culture results were documented. Highly sensitive serum CRP was measured according to hospital protocol, while salivary CRP levels were measured using enzyme-linked immunosorbent assay. ResultsThe median serum CRP was significantly higher in septic neonates compared to controls (p < 0.001). For serum CRP, the optimum cut-off value for LOS diagnosis was found to be 7.2 mg/L with sensitivity, specificity, positive and negative predictive values of 91, 100, 100, and 85.7%, respectively. No significant difference was observed in levels of salivary CRP among the 3 study groups (p = 0.39). No correlation was found between the levels of salivary and serum CRP (r = 0.074, p = 0.49). ConclusionSerum CRP, at a cut-off value of 7.2 mg/L, exhibited a high specificity and positive predictive value in LOS diagnosis, whereas salivary CRP levels weren’t significantly different between the 3 study groups nor did they predict abnormal serum CRP thresholds in newborns with sepsis.

Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis.

The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia. A nonmatched case-control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS). Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35-112]) were identified as risk factors for NS. Differences in CRP (p < 0.0001) and IL-6 (p < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 (p < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 (p = 0.0315) and the optimal cutoff was 17.75 pg/mL. Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group. · NS is a major morbimortality cause worldwide. · CRP and IL-6 levels may be useful NS biomarkers. · No biomarker alone is enough for the diagnosis of NS.

Stromal-derived factor-1 (CXCL12) and its receptor (CXCR4) in neonatal sepsis

Background Neonatal sepsis remains a major cause of morbidity and mortality in newborns. The C-X-C motif chemokine 12 (CXCL12) and its receptor α-chemokine receptor type 4 (CXCR4) are now known to play an important role in inflammatory states and mediate lymphocyte migration in response inflammation. However, it is unclear how chemokines respond to late-onset neonatal sepsis (LOS). Objective The aim of this study was to assess the value of measuring the serum levels of stromal-derived factor-1, also named CXCL12, and lymphocyte expression levels of its receptor CXCR4 in the diagnosis of LOS in relation to clinical and hematological sepsis scores. Patients and methods Levels of CXCL12 in serum and lymphocyte expression of CXCR4 were determined using enzyme-linked immunosorbent assay technique and flow cytometry, respectively, in 38 full-term neonates; 23 cases of LOS (13 male and 10 female) and 15 healthy neonates (six male and nine female) were included in the study. Results Serum levels of CXCL12 and lymphocyte expression levels of CXCR4 were significantly higher in neonates with LOS when compared with nonseptic neonates. At a cutoff point of 30 pg/ml, the diagnostic accuracy of CXCL12 in the diagnosis of neonatal sepsis was 100%, with a sensitivity of 100% and a specificity of 100%, whereas the diagnostic accuracy of mean fluorescence intensity of lymphocyte expression of CXCR4 in the diagnosis of neonatal sepsis was 84%, with a sensitivity of 87%, specificity of 80%, positive predictive value of 87%, and negative predictive value of 80% at a cutoff point of 150. Conclusion CXCR4 and CXCL12 levels increase significantly in septic neonates and they are valuable markers in the diagnosis of neonatal sepsis.

Screening and Serial Neutrophil Counts Do Not Contribute to the Recognition or Diagnosis of Late-Onset Neonatal Sepsis

To determine the validity of screening and serial neutrophil counts in predicting the absence/presence of late-onset sepsis (LOS) in infants with central venous catheters. Retrospective study of infants admitted to the neonatal intensive care unit (2009-2013) at Parkland Hospital with a central venous catheter and ≥1 LOS evaluations. Infants were categorized as proven or suspect LOS or uninfected based on results of blood cultures, clinical illness, and duration of antibiotics. Receiver operating curves (ROCs) were constructed to predict the absence or presence of LOS using Manroe reference ranges for total and immature neutrophils and the immature to total neutrophil ratio at 0, 12, and 24 hours after blood culture and the neutrophil value score, which assesses serial values. Of the 497 infants with a central venous catheter, 179 underwent ≥1 LOS evaluations, and 140 of 179 (78%) had ≥1 complete evaluations (2 blood cultures and neutrophil values at 0, 12, and 24 hours), resulting in 188 complete LOS evaluations. The gestational age was 28 ± 4 weeks and LOS evaluation occurred at 29 ± 34 days (SD; 4-197 days). Sixty-one (35%) infants had proven LOS, 48 (23%) were suspect, and 71 (38%) were noninfected. ROC comparing proven vs noninfected was ≤0.56 for total neutrophils, immature neutrophils, and immature to total neutrophil ratio at 0, 12, and 24 hours and similar for proven + suspect vs noninfected. ROC for neutrophil value scores and absence of LOS was 0.56. Screening neutrophil values are poor predictors of LOS in neonates with a central venous catheter, as are serial neutrophils and the neutrophil value score. Alternative biomarkers are needed.

Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants

Objective: One of the most challenging aspects in the management of neonates with late-onset neonatal sepsis (LOS) is to make the diagnosis. Presepsin is a novel and promising marker of sepsis. The aim of this study was to assess the role of presepsin in the diagnosis of LOS in preterm infants.Methods: Forty-two premature newborns ≤32 weeks gestational age with a diagnosis of LOS were prospectively involved in the study. Forty gestational and postnatal age-matched infants without sepsis served as controls. Levels of presepsin, C-reactive protein, and procalcitonin were measured at enrollment and on the third and seventh days of sepsis.Results: Initial presepsin levels in the LOS group were significantly higher than in the control group (1024 pg/mL, min–max: 295–8202; versus 530 pg/mL, min–max: 190–782; p < 0.0001). The area under the receiver-operating curve for presepsin was 0.864. A presepsin value of 800.5 pg/mL was established as a cut-off value, with 67% sensitivity and 100% specificity. Presepsin levels gradually decreased during treatment.Conclusion: Presepsin can be used as a reliable biomarker for LOS and treatment response in preterm infants. However, we could not demonstrate the efficacy of presepsin for the detection of disease severity or prognosis.

The value of lipopolysaccharide binding protein for diagnosis of late-onset neonatal sepsis in very low birth weight infants.

To assess the accuracy of lipopolysaccharide binding protein (LBP) for diagnosing late-onset neonatal sepsis (LONS) in very low birth weight (VLBW) infants. Observational, prospective study. We assessed the diagnostic performance of LBP in 26 suspected LONS episodes among 54 patients. Proven and probable LONS episodes were recorded according to established criteria. Receiver operating characteristic curve analysis was performed to evaluate LBP's ability to predict LONS. LONS was diagnosed in 17 of 26 episodes. LBP levels were significantly higher in confirmed LONS episodes (P<0.001). The area under the curve of LBP was 0.89. A cut-off of 17.5 μg/mL had a sensitivity of 94.1%, a specificity of 77.8%, a positive predictive value of 88.9% and a negative predictive value of 87.5%. Serum LBP measurement may be useful as an additional tool in the evaluation of suspected LONS in VLBW infants.

Central-peripheral temperature gradient: an early diagnostic sign of late-onset neonatal sepsis in very low birth weight infants

We assessed central-peripheral temperature gradient alteration for the diagnosis of late-onset neonatal sepsis and compared earliness detection of this sign with altered blood cell count and C-reactive protein. Thirty-one preterm babies (<1500 g or <32 weeks) participated in an observational prospective study. Axillary (central) and sole (peripheral) temperatures were continuously monitored with a thermal probe (ThermoTracer; Dräger Medical AGF & Co. KgaA, Lübeck, Germany) adjusting incubator air temperature for a thermal gradient <1.5°C. Central-peripheral temperature alteration was defined as a thermal gradient >2°C that could not be corrected with protocolized air temperature modifications. Proven (positive blood culture) sepsis and probable late-onset sepsis were recorded. Late-onset sepsis was diagnosed in 11 neonates (proven, 9; probable, 2). Thermal gradient alteration was present in 12 cases, in association with the onset of sepsis in 10 and concomitantly with a ductus arteriosus and stage 1 necrotizing enterocolitis in 2. Thermal gradient alteration had a sensitivity of 90.9% [95% confidence interval (CI), 62.3-98.4] and specificity of 90% (95% CI, 69.9-97.2%), and in 80% of cases, it occurred before abnormal laboratory findings. Central-peripheral temperature gradient monitoring is a feasible, non-invasive, and simple tool easily applicable in daily practice. An increase of >2°C showed a high-sensitivity and specificity for the diagnosis of late-onset sepsis.

Can we rely on procalcitonin in the diagnosis of late onset neonatal sepsis?

Aims(1) To explore the usefulness of procalcitonin (PCT) assay in the diagnosis of late onset neonatal sepsis (LONS). (2) To compare the diagnostic usefulness of PCT with C reactive protein...

Nearest-Neighbor and Logistic Regression Analyses of Clinical and Heart Rate Characteristics in the Early Diagnosis of Neonatal Sepsis

To test the hypothesis that nearest-neighbor analysis adds to logistic regression in the early diagnosis of late-onset neonatal sepsis. The authors tested methods to make the early diagnosis of neonatal sepsis using continuous physiological monitoring of heart rate characteristics and intermittent measurements of laboratory values. First, the hypothesis that nearest-neighbor analysis makes reasonable predictions about neonatal sepsis with performance comparable to an existing logistic regression model was tested. The most parsimonious model was systematically developed by excluding the least efficacious clinical data. Second, the authors tested the hypothesis that a combined nearest-neighbor and logistic regression model gives an outcome prediction that is more plausible than either model alone. Training and test data sets of heart rate characteristics and laboratory test results over a 4-y period were used to create and test predictive models. Nearest-neighbor, regression, and combination models were evaluated for discrimination using receiver-operating characteristic areas and for fit using the Wald statistic. Both nearest-neighbor and regression models using heart rate characteristics and available laboratory test results were significantly associated with imminent sepsis, and each kind of model added independent information to the other. The best predictive strategy employed both kinds of models. The authors propose nearest-neighbor analysis in addition to regression in the early diagnosis of subacute, potentially catastrophic illnesses such as neonatal sepsis, and they recommend it as an approach to the general problem of predicting a clinical event from a multivariable data set.

External validation of bedside prediction score for diagnosis of late-onset neonatal sepsis

To prospectively validate performance of a prediction score for diagnosis of late-onset neonatal sepsis (LNS) in a new patient population. Data were prospectively collected from March 2003 to May 2004. Newborns were enrolled if they were in the neonatal intensive care unit (NICU) between 2 and 90 days, and during the first episode of clinical sepsis suspected. LNS was defined as a positive blood or cerebrospinal fluid (CSF) culture, which became the criterion standard. A total of 105 neonates were evaluated for sepsis. Demographic characteristics were as follows: (mean (s.d.)) were gestational age (GA) 29 (3) weeks; birth weight (BW) 1232 (620) g and postnatal age 17.5 day (12). Thirty-five (33%) neonates had LNS (35 positive blood cultures; 2 positive CSF). No significant differences in GA, BW, gender, age and central line utilization were found between LNS positive and LNS negative groups. Using a cut-off score of < or = 3, the score predicted positive culture with sensitivity of 0.97 (95% confidence interval 0.85, 0.99) and a negative likelihood ratio of 0.07. The discrimination and calibration ability of LNS score was acceptable. A simple clinical decision rule previously developed to predict LNS performs equally in an independent population and NICU.