Diagnosis Of Serious Bacterial Infections Research Articles

Low adherence to a new guideline for managing febrile infants ≤59 days.

Management of young febrile infants is challenging. Therefore, several guidelines have been developed over the last decades. However, knowledge regarding the impact of introducing guidelines for febrile infants is limited. We assessed the impact of and adherence to a novel guideline for managing febrile infants aged ≤59 days. This retrospective cross-sectional study was conducted in 2 pediatric emergency departments in Sweden between 2014 and 2021. We compared the management of infants aged ≤59 days with fever without a source (FWS) and the diagnosis of serious bacterial infections (SBIs) before and after implementing the new guideline. We included 1,326 infants aged ≤59 days with FWS. Among infants aged ≤21 days, urine cultures increased from 49% to 67% (p = 0.001), blood cultures from 43% to 63% (p < 0.001), lumbar punctures from 16% to 33% (p = 0.003), and antibiotics from 38% to 57% (p = 0.002). Only 39 of 142 (28%) infants aged ≤21 days received recommended management. The SBI prevalence was 16.7% (95% CI, 11.0-23.8) and 17.6% (95% CI, 11.7-24.9) before and after the implementation, respectively. Among infants aged ≤59 days, there were 3 infants (0.6%; 95% CI, 0.1-1.7) in the pre-implementation period and 3 infants (0.6%; 95% CI, 0.1-1.7) in the post-implementation period with delayed treated urinary tract infections. Investigations and antibiotics increased significantly after implementation of the new guideline. However, doing more did not improve the diagnosis of SBIs. Thus, the low adherence to the new guideline may be considered justified. Future research should consider strategies to safely minimize interventions when managing infants with FWS.

Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study

The diagnosis of serious bacterial infection (SBI) in young febrile children remains challenging. This prospective, multicentre, observational study aimed to identify new protein marker combinations that can differentiate a bacterial infection from a viral infection in 983 children, aged 7 days-36 months, presenting with a suspected SBI at three French paediatric emergency departments. The blood levels of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) were measured at enrolment. The patients received the standard of care, blinded to the biomarker results. An independent adjudication committee assigned a bacterial vs. viral infection diagnosis based on clinical data, blinded to the biomarker results. Computational modelling was applied to the blood levels of the biomarkers using independent training and validation cohorts. Model performances (area under the curve (AUC), positive and negative likelihood ratios (LR+ and LR-)) were calculated and compared to those of the routine biomarkers CRP and PCT. The targeted performance for added value over CRP or PCT was LR+ ≥ 5.67 and LR- ≤ 0.5. Out of 652 analysed patients, several marker combinations outperformed CRP and PCT, although none achieved the targeted performance criteria in the 7 days-36 months population. The models seemed to perform better in younger (7-91 day-old) patients, with the CRP/MxA/TRAIL combination performing best (AUC 0.895, LR+ 10.46, LR- 0.16). Although computational modelling using combinations of bacterial- and viral-induced host-protein markers is promising, further optimisation is necessary to improve SBI diagnosis in young febrile children.

Utility of the systemic immune-inflammation index to predict serious bacterial infections in infants with fever without a source

ABSTRACT Introduction This study analyzed the utility of the systemic immune-inflammation index (SII) in predicting serious bacterial infections (SBIs) in infants with fever without a source (FWS). Methods Infants (aged 1–4 months) evaluated in the pediatric emergency department for FWS were divided into two groups: with SBI and without SBI. The efficacy of inflammatory markers in predicting SBI was compared. Results The study included 223 infants with a mean age of 76.65 ± 25.42 days; 62 (27.8%) of them were included in the SBI group, and all of them were diagnosed with a urinary tract infection (UTI). The hospitalization rate and length of hospital stay were significantly higher in UTI patients (p < 0.001 for each). The mean SII was 795.76 ± 475.85 in the SBI group and 318.24 ± 300.70 in the non-SBI group, and there was a significant difference between the groups (p < 0.001). In diagnosis of SBI, the area under the curve values were found to be 0.89 [95% confidence interval (CI): 0.85–0.94] for C-reactive protein (CRP), 0.86 (95% CI: 0.81–0.91) for absolute neutrophil count (ANC), 0.84 (95% CI: 0.78–0.89) for the SII, and 0.81 (95% CI: 0.74–0.87) for WBC. In the multivariate logistic regression analysis, high CRP and SII values were found to be predictive factors for UTI without bacteremia (p < 0.001 and p = 0.008, respectively). Conclusion We found that high CRP and SII values could be predictive for UTI without bacteremia in infants with FWS. The SII may be preferred because it can be easily calculated using the hemogram results, is not accompanied by extra costs, and does not require further blood collection.

Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study.

Serious bacterial infections (SBI) in children are associated with considerable morbidity and mortality, and their early identification remains challenging. The role of laboratory tests in this setting is still debated, and new biomarkers are needed. This prospective, observational, single-center study aims to evaluate the diagnostic role of blood biomarkers in detecting SBI in children presenting with signs of systemic inflammatory response syndrome (SIRS). A panel of biomarkers was performed, including C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p = 0.001) and ICAM-1 (p = 0.043). WBC (p = 0.035), ANC (p = 0.012) and ANC/WBC ratio (p = 0.015) were also significantly associated with SBI in children without pre-existing neutropenia. ROC curves, however, revealed suboptimal performance for all variables. Nevertheless, a model that combined CRP and ANC/WBC ratio had more in-depth diagnostic accuracy than either of the two variables. Overall, this study confirms the limited usefulness of blood biomarkers for the early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP, and ICAM-1 showed the best, albeit moderate, diagnostic accuracy.

Procalcitonin, C-reactive protein, neutrophil gelatinase-associated lipocalin, resistin and the APTT waveform for the early diagnosis of serious bacterial infection and prediction of outcome in critically ill children.

Bacterial Infections remains a leading cause of death in the Paediatric Intensive Care Unit (PICU). In this era of rising antimicrobial resistance, new tools are needed to guide antimicrobial use. The aim of this study was to investigate the accuracy of procalcitonin (PCT), neutrophil gelatinase-associated lipocalin (NGAL), resistin, activated partial thromboplastin time (aPTT) waveform and C-reactive protein (CRP) for the diagnosis of serious bacterial infection (SBI) in children on admission to PICU and their use as prognostic indicators. A regional PICU in the United Kingdom. Consecutive PICU admissions between October 2010 and June 2012. Blood samples were collected daily for biomarker measurement. The primary outcome measure was performance of study biomarkers for diagnosis of SBI on admission to PICU based on clinical, radiological and microbiological criteria. Secondary outcomes included durations of PICU stay and invasive ventilation and 28-day mortality. Patients were followed up to day 28 post-admission. A total of 657 patients were included in the study. 92 patients (14%) fulfilled criteria for SBI. 28-day mortality was 2.6% (17/657), but 8.7% (8/92) for patients with SBI. The combination of PCT, resistin, plasma NGAL and CRP resulted in the greatest net reclassification improvement compared to CRP alone (0.69, p<0.005) with 10.5% reduction in correct classification of patients with SBI (p 0.52) but a 78% improvement in correct classification of patients without events (p <0.005). A statistical model of prolonged duration of PICU stay found log-transformed maximum values of biomarkers performed better than first recorded biomarkers. The final model included maximum values of CRP, plasma NGAL, lymphocyte and platelet count (AUC 79%, 95% CI 73.7% to 84.2%). Longitudinal profiles of biomarkers showed PCT levels to decrease most rapidly following admission SBI. Combinations of biomarkers, including PCT, may improve accurate and timely identification of SBI on admission to PICU.

Shivering has little diagnostic value in diagnosing serious bacterial infection in children: a systematic review and meta-analysis.

Early diagnosis of serious bacterial infections (SBI) is important for improving outcome of morbidity and mortality in children. A systematic review was conducted to examine if shivering had any value in diagnosing serious bacterial infection. We split our population (0-18 years old) into two categories depending on the presence of a known malignancy. The databases of Medline, Embase, Cinahl, and Web of Science were searched from inception until July 2019. The quality was assessed with the QUADAS-2 tool. Two by two tables were created, extracting the number of true positive (TP), true negative (TN), false positive (FP), and false negative (FN) regarding shivering and SBI, by 2 authors independently. Sensitivity, specificity, likelihood ratios, and their 95% confidence intervals were calculated using the MetaDATA Shiny app. In a population with known malignancy, we found a +LR of 3.47 (95% CI 2.58-4.36) for a serious bacterial infection when shivering was present, implying an increase of 25-30% possibility for a serious bacterial infection. In children without malignancy, diagnostic accuracy of shivering was poor.Conclusion: Shivering is of limited use to diagnose serious bacterial infection in children without malignancy. Nevertheless, in children with known malignancy, it can be useful as an alarm signal. What is Known: • In the NICE guidelines for febrile illness in children, "shivering" is considered as an intermediate risk factor ("amber" sign) for a serious illness. • A systematic literature search conducted in 2007 investigating the correlation between shivering in a febrile child and the presence of a serious bacterial infection could include only one study. What is New: • Based on the results of this systematic review, shivering has little diagnostic value in children without malignancy but can be useful as an alarm sign of serious bacterial infection in children with known malignancy. • In case of absence of shivering, serious bacterial infection cannot be ruled out.

Diagnostic test accuracy of point-of-care procalcitonin to diagnose serious bacterial infections in children

BackgroundThe National Institute for Health and Care Excellence (NICE) have called for research into the role of biomarkers, and specifically procalcitonin (PCT), for the early diagnosis of serious bacterial infections (SBI) in children. The aim of this study was to compare the diagnostic test accuracy of C-reactive protein (CRP) and PCT for the diagnosis of SBI in children.MethodsData was collected prospectively from four UK emergency departments (ED) between November 2017 and June 2019. Consecutive children under 18 years of age with fever and features of possible sepsis and/or meningitis were eligible for inclusion. The index tests were PCT and CRP and the reference standard was the confirmation of SBI.Results213 children were included in the final analysis. 116 participants (54.5%) were male, and the median age was 2 years, 9 months. Parenteral antibiotics were given to 100 (46.9%), three (1.4%) were admitted to a paediatric intensive care unit and there were no deaths. There were ten (4.7%) confirmed SBI. The area under the curve for PCT and CRP for the detection of SBI was identical at 0.70.ConclusionsThere was no difference in the performance of PCT and CRP for the recognition of SBI in this cohort.Trial registrationRegistered at https://www.clinicaltrials.gov (trial registration: NCT03378258) on the 19th of December 2017.

Utility of basic clinical and laboratory parameters to predict Serious Bacterial Infection in children younger than 3 months old hospitalized for Febrile Syndrome without Source.

In 20% of children with febrile syndrome, it appears as fever of unknown origin (FUO) syndrome. Management strategies in this group have high sensitivity but low specificity. To cha racterize serious bacterial infections (SBI) in children younger than three months old hospitalized because of FUO syndrome and to evaluate the utility of clinical and laboratory parameters in the identification of patients that are at high risk of SBI. Prospective study in patients aged < 3 months hospitalized due to FUO syndrome between January 2014 and November 2015 in two pediatric hospitals in the Metropolitan Region. age 4 days - 3 months, fever > 38°C longer than 72 hours after onset without demonstrable cause. anti microbial use up to 7 days before admission, preterm infants < 34 weeks, birth weight < 2 kg, and im munocompromised. Demographic, clinical, and laboratory tests data were recorded as well as blood count and CRP, discharge diagnosis, and ruled out, probable or confirmed SBI. 32% of the patients were discharged with diagnosis of SBI, 28% with diagnosis of viral or probably viral infec tion, 34% with diagnosis of not specified FUO syndrome, and 6% due to other causes. There were no significant differences in the CRP value, altered WBCs count, toxic aspect, or hours of fever at the admission when comparing groups with and without SBI (p < 0.05). The combination of clinical and laboratory parameters showed 27% of sensitivity, 90% of specificity, 60% of PPV, and 71% of NPV. It was not possible to establish clinical and laboratory parameters that allow the identifi cation of children younger than 3 months old at high risk of SBI, however, they maintain their value as low risk indicators. It is necessary further investigation of other clinical and laboratory elements that allow discriminating SBI from viral infections.

Are parents' statements reliable for diagnosis of serious bacterial infection among children with fever without an apparent source?: A retrospective study.

Serious bacterial infection (SBI) is a major cause of morbidity and mortality in children. Distinguishing SBI from self-limiting viral infections is a very important task in the emergency department (ED), especially in the children with fever without source (FWS). The aim of this study was to analyze whether parents’ statements about clinical manifestations, which were categorized according to grades, are related to the actual diagnosis of SBI in children with FWS.Retrospective analysis was conducted using prospectively acquired cohort data for all febrile children in the pediatric ED of Seoul National University Hospital from August 2016 to August 2017. The association of clinical manifestations and SBI was the main outcome of this study. The SBIs included diagnoses such as bacteremia, bacterial meningitis, urinary tract infection, and pneumonia. Clinical manifestations including activity, urination, and feeding were categorized into 3 or 4 grades according to the parents’ statements. The linear-by-linear association test was used to examine linear associations between the severity of clinical manifestations and SBI. Receiver operating characteristic curves for clinical manifestations were constructed for patients with SBI. Area under the curve (AUC) statistics and 95% confidence intervals (CIs) were obtained to evaluate the predictive performance of clinical manifestations.There was no linear association between SBI and non-SBI when compared by severity of the clinical manifestations, such as duration of fever (P = .299), activity (P = .781), feeding (P = .161), and urination (P = .834). The AUC was 0.54 (95% CI 0.41–0.67) for duration of fever, 0.52 for activity (95% CI 0.40–0.64), 0.42 for feeding (95% CI 0.32–0.53), and 0.51 for urination (95% CI 0.39–0.62).There was no evidence that the test performance of the clinical manifestations is valid for predicting SBIs, even considering the severity of manifestations. For optimal evaluation of the children with FWS, more comprehensive approach including laboratory tests, are needed.

Performance of prediction rules and guidelines in detecting serious bacterial infections among Tanzanian febrile children

BackgroundHealth-workers in developing countries rely on clinical algorithms, such as the Integrated Management of Childhood Illnesses (IMCI), for the management of patients, including diagnosis of serious bacterial infections (SBI). The diagnostic accuracy of IMCI in detecting children with SBI is unknown. Prediction rules and guidelines for SBI from well-resourced countries at outpatient level may help to improve current guidelines; however, their diagnostic performance has not been evaluated in resource-limited countries, where clinical conditions, access to care, and diagnostic capacity differ. The aim of this study was to estimate the diagnostic accuracy of existing prediction rules and clinical guidelines in identifying children with SBI in a cohort of febrile children attending outpatient health facilities in Tanzania.MethodsStructured literature review to identify available prediction rules and guidelines aimed at detecting SBI and retrospective, external validation on a dataset containing 1005 febrile Tanzanian children with acute infections. The reference standard, SBI, was established based on rigorous clinical and microbiological criteria.ResultsFour prediction rules and five guidelines, including IMCI, could be validated. All examined rules and guidelines had insufficient diagnostic accuracy for ruling-in or ruling-out SBI with positive and negative likelihood ratios ranging from 1.04–1.87 to 0.47–0.92, respectively. IMCI had a sensitivity of 36.7% (95% CI 29.4–44.6%) at a specificity of 70.3% (67.1–73.4%). Rules that use a combination of clinical and laboratory testing had better performance compared to rules and guidelines using only clinical and or laboratory elements.ConclusionsCurrently applied guidelines for managing children with febrile illness have insufficient diagnostic accuracy in detecting children with SBI. Revised clinical algorithms including simple point-of-care tests with improved accuracy for detecting SBI targeting in tropical resource-poor settings are needed. They should undergo careful external validation against clinical outcome before implementation, given the inherent limitations of gold standards for SBI.

Antibiotic Susceptibility Test with Surface-Enhanced Raman Scattering in a Microfluidic System.

Antibiotic susceptibility test (AST) is essential in clinical diagnosis of serious bacterial infection, such as sepsis, while it typically takes 2-5 days for sample culture, antibiotic treatment, and reading result. Detecting metabolites secreted from bacteria with surface-enhanced Raman scattering (SERS) enables rapid determination of antibiotic susceptibility, reducing the AST time to 1-2 days. However, it still requires 1 day of culture time to obtain sufficient quantity of bacteria for sample washing, bacterial extraction, and antibiotic treatment. Additionally, the whole procedure, manually performed in open environment, often suffers from contamination and human error. To address the above problems, a microfluidic system integrating membrane filtration and the SERS-active substrate (MF-SERS) was developed to perform on-chip bacterial enrichment, metabolite collection, and in situ SERS measurements for antibiotic susceptibility test. Using Escherichia coli as the prototype bacterium, the lowest SERS detection limit of bacterial concentration of the MF-SERS system is 103 CFU/mL, which is 4 orders of magnitude lower than that using centrifugation-purification procedure, significantly shortening the bacterial culture time. The bacteria and secreted metabolites are enclosed during bacterial trapping, metabolite filtration, and SERS detection, thus minimizing possible contamination and human errors. Finally, the successful demonstration of AST on E. coli with a concentration of 103 CFU/mL is presented. Overall, the MF-SERS system with a miniature size and well-confined microenvironment allows the integration of multiple bacteria processes for bacterial enrichment, culture, and determination of AST.

Parents’ and clinicians’ views on conducting paediatric diagnostic test accuracy studies without prior informed consent: qualitative insight from the Petechiae in Children study (PiC)

ObjectiveThe Petechiae in Children (PiC) study assesses the utility of presenting features and rapid diagnostic tests in the diagnosis of serious bacterial infection in feverish children with non-blanching rashes. An...

Positive Viral Tests in Febrile Young Infants: Do They Matter?

Research Article| March 01 2019 Positive Viral Tests in Febrile Young Infants: Do They Matter? AAP Grand Rounds (2019) 41 (3): 30. https://doi.org/10.1542/gr.41-3-30 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Positive Viral Tests in Febrile Young Infants: Do They Matter?. AAP Grand Rounds March 2019; 41 (3): 30. https://doi.org/10.1542/gr.41-3-30 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: fever, bacterial infection, serious Source: Mahajan P, Browne LR, Levine DA, et al. Risk of bacterial coinfections in febrile infants 60 days old and younger with documented viral infections. J Pediatr. 2018; 203: 86.e2– 91.e2. doi: https://doi.org/10.1016/j.jpeds.2018.07.073Google Scholar Investigators from multiple institutions conducted a secondary analysis of data collected during a large prospective study in febrile infants ≤60 days old to assess the risk of serious bacterial infection (SBI) in patients with a documented viral infection. The original study was conducted by the Pediatric Emergency Care Applied Research Network and included children ≤60 days old, with a temperature >38.0°C, presenting to 1 of 26 EDs. Demographic information, physical examination findings, and laboratory results were collected for enrolled patients. For the current analysis, only study participants who were tested for at least one virus were included. The primary study outcome was the presence of an SBI, including UTI, bacteremia, or bacterial meningitis. The diagnosis of SBI was based on blood, urine, and cerebrospinal fluid culture results. For study patients in whom lumbar puncture was not performed, the absence of bacterial meningitis was confirmed based on telephone contact with the infants’ parents 7 days after the index visit. The rates of any SBI and each individual SBI were compared among viral-positive and viral-negative infants and the risk ratio (RR) calculated; analyses limited to children ≤28 days old and >28 days old were also conducted. Among the 4,788 infants enrolled in the original study, 3,072 (64.3%) had testing for at least one virus. Among these 3,072 infants, 2,945 (95.9%) who also had complete ascertainment for the presence of an SBI were included in the current analyses, of whom 1,200 (48.1%) had a positive test for ≥1 virus. The rate of SBI in viral-positive infants was 3.7% (95% CI, 2.7%–4.9%) compared to 12.7% (95% CI, 11.2%–14.4%) for those who were virus-negative (RR, 3.5; 95% CI, 2.5–4.8). Rates of UTI (2.8% and 10.7%, respectively) and bacteremia (0.8% and 2.9%, respectively) were also significantly lower in viral-positive infants than in viral-negative infants. Bacterial meningitis was diagnosed in 0.4% of viral-positive infants compared to 0.8% in viral-negative infants (RR, 1.9; 95% CI, 0.7%–5.3%). Among infants who were ≤28 days old and those who were >28 days old, the risk of SBI was significantly lower in viral-positive infants (RR, 4.0; 95% CI, 2.4–6.6 and RR, 2.9; 95% CI, 1.9–4.3, respectively). The authors conclude that, although the rate of SBI is lower in febrile infants ≤60 days old who have a documented viral infection than in those who are viral negative, viral-positive infants are still at nonnegligible risk for SBI. Dr Stevenson has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Substantial variation in the evaluation of the young febrile infant exists across pediatric EDs in the United States at both the patient and hospital levels.1 In the present study, viral testing via rapid antigen testing, immunofluorescence,... You do not currently have access to this content.

Diagnostic markers of serious bacterial infections in infants aged 29 to 90 days

Objectives: The diagnosis of serious bacte-rial infection (SBI) is difficult due to a lack of clinical evidence. The purpose of this study was to determine which inflamma-tory markers can be used to detect SBI in febrile infants.Methods: This retrospective cohort study included infants aged 29 to 90 days who visited a tertiary hospital emergency de-partment in Korea between July 2016 and June 2018. The diagnostic characteristics of the neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC) count, and absolute neutrophil cell (ANC) count for detecting SBI were described. Their cutoff values were calculated based on receiver operating characteristic (ROC) curve analysis.Results: Among 528 infants, 199 were finally enrolled. SBI was detected in 68 (34.2%) of these infants. The median val-ues of all investigated diagnostic markers were significantly higher in infants with SBI than the values in those without: WBC (12.72 vs. 9.91 k/μL), ANC (6.28 vs. 3.14 k/μL), CRP (26.6 vs. 2.8 mg/L), NLR (1.29 vs. 0.78), and PCT (0.5 vs. 0 ng/mL). The areas under the ROC curves for discriminating SBI were: 0.705 (95% confidence interval [CI], 0.629-0.781), 0.793 (95% CI, 0.731-0.856), 0.832 (95% CI, 0.775-0.889), 0.722 (95% CI, 0.651-0.792), and 0.695 (95% CI, 0.611-0.780) for WBC, ANC, CRP, NLR, and PCT, respectively. Using a cutoff value of 0.67 for NLR, the negative predictive value was 90.8% for identifying SBI. Conclusions: CRP was the best single dis-criminatory marker of SBI, while NLR was the best parameter for considering dis-charge.

Evaluation and Validation of a Model for Identifying Serious Bacterial Infections among Children Presenting to the Emergency: Evidence-based Medicine Viewpoint.

In this diagnostic accuracy study of clinical and biomarker variables in the diagnosis of serious bacterial infections (SBIs), including pneumonia, in febrile children (age <16 y), a diagnostic model was derived by using multinomial logistic regression and internal validity. External validation of a published model was undertaken, followed by model updating and extension by the inclusion of procalcitonin and resistin. There were 1101 children studied, of whom 264 had a SBI. A diagnostic model discriminated well between pneumonia and no SBI (concordance statistic 0.84, 95% CI 0.78–0.90) and between other SBIs and no SBI (0.77, 95% CI 0.71–0.83) on internal validation. A published model discriminated well on external validation. Model updating yielded good calibration with good performance at both high-risk (positive likelihood ratios 6.46 and 5.13 for pneumonia and other SBI, respectively) and low-risk (negative likelihood ratios 0.16 and 0.13, respectively) thresholds. Extending the model with procalcitonin and resistin yielded improvements in discrimination. The authors concluded that diagnostic models discriminated well between pneumonia, other SBIs, and no SBI in febrile children in the emergency department.

Predicting Risk of Serious Bacterial Infections in Febrile Children in the Emergency Department.

Improving the diagnosis of serious bacterial infections (SBIs) in the children's emergency department is a clinical priority. Early recognition reduces morbidity and mortality, and supporting clinicians in ruling out SBIs may limit unnecessary admissions and antibiotic use. A prospective, diagnostic accuracy study of clinical and biomarker variables in the diagnosis of SBIs (pneumonia or other SBI) in febrile children <16 years old. A diagnostic model was derived by using multinomial logistic regression and internally validated. External validation of a published model was undertaken, followed by model updating and extension by the inclusion of procalcitonin and resistin. There were 1101 children studied, of whom 264 had an SBI. A diagnostic model discriminated well between pneumonia and no SBI (concordance statistic 0.84, 95% confidence interval 0.78-0.90) and between other SBIs and no SBI (0.77, 95% confidence interval 0.71-0.83) on internal validation. A published model discriminated well on external validation. Model updating yielded good calibration with good performance at both high-risk (positive likelihood ratios: 6.46 and 5.13 for pneumonia and other SBI, respectively) and low-risk (negative likelihood ratios: 0.16 and 0.13, respectively) thresholds. Extending the model with procalcitonin and resistin yielded improvements in discrimination. Diagnostic models discriminated well between pneumonia, other SBIs, and no SBI in febrile children in the emergency department. Improvements in the classification of nonevents have the potential to reduce unnecessary hospital admissions and improve antibiotic prescribing. The benefits of this improved risk prediction should be further evaluated in robust impact studies.

The Diagnostic Significance of Hemogram Indicators and Serum Markers of Inflammation in Serious Bacterial Infections in Children Under 5 Years of Age

Background: Diagnosis of serious bacterial infections (SBI) in young children is a difficult task for pediatricians. Objective: Our aim was to determine regularities of the change of hemogram indicators and serum markers of inflammation for the differential diagnostics of SBI in children under the age of 5 years. Methods: The comparative retrospective study is carried out. We analyzed diagnostic characteristics of laboratory markers of SBI during the examination of 306 children with pyretic fever. We determined the number of leukocytes, neutrophils, immature granulocytes, reticulocyte hemoglobin equivalent, C-reactive protein (CRP) and procalcitonin. Results: The study of CRP content has the greatest diagnostic accuracy at differential diagnostics of SBI in children with infectious fever at the height of disease. It is established that the positive result of CRP ( 37 mg/L) increases the probability of SBI in patient from 17.6% to 70%, and the negative result (< 37 mg/L) reduces the probability of SBI to 4%. Conclusion: Cut-off values of the laboratory parameters obtained in our study can be used when assessing the post-test probability of SBI in children with infections accompanied by pyretic fever.

RNA transcriptional biosignature analysis for identifying febrile infants with serious bacterial infections in the emergency department: a feasibility study.

To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression analysis. It is possible to create a robust infrastructure to conduct genomic studies in young febrile infants in the context of a multicenter pediatric ED research setting. The sufficient quantity and high quality of RNA obtained suggests that whole blood transcriptional profile analysis for the diagnostic evaluation of young febrile infants can be successfully performed in this setting.

Is Procalcitonin Useful in Early Diagnosis of Serious Bacterial Infections in Children?

Introduction: Diagnosis of bacterial infections remains one of the greatest challenges in medical science, especially in children, in whom clinical signs are often nonspecific. The currently used sepsis screen has poor predictive value. Recently introduced marker procalcitonin (PCT) with high sensitivity and specificity is evaluated as early marker of serious bacterial infection in children. Materials and Methods: Children up to 5 years of age presenting with features of Systemic Inflammatory Response Syndrome(SIRS) were evaluated clinically and underwent standard sepsis screen namely total leukocyte count (TLC), peripheral blood smear for band count, C-reactive Protein (CRP) and newer tests like procalcitonin (PCT) and Interleukin-8 (IL-8). Results were analyzed using SPSS14.0. Results: One hundred patients suspected of sepsis were evaluated. Maximum cases were below one year (37%) with mean age of 27 months. Male:female ratio was 1.5:1. Respiratory system was the commonest system involved in (54%) followed by gastrointestinal (20%), genitourinary (10%) and central nervous system (5%). Seventy two cases were found to have confirmed sepsis, proven by blood culture (34%) and other investigations. Fifty two cases were diagnosed by conventional markers, while newer markers in 60 cases. Diagnostic evaluation revealed that newer markers have higher sensitivity and specificity as compared to conventional sepsis screen. Conclusion: Procalcitonin is a useful marker for diagnosis of serious bacterial infections in children and in combination with IL8 has a higher sensitivity and specificity as compared to standard sepsis screen. Therefore it is recommended that procalcitonin should be used for the screening of sepsis in children so that the treatment can be started earlier in order to prevent morbidity and mortality. DOI: http://dx.doi.org/10.3126/jnps.v33i2.7988 J Nepal Paediatr Soc. 2013; 33(2):106-109

1578 The Correlation Between C-Reactive Protein and Serious Bacterial Infection in a Tertiary Paediatric Emergency Department: An Observational Case-Controlled Cohort Study

Background and AimsC-Reactive Protein (CRP) is a common component of the blood panel in children being investigated for the considered diagnosis of serious bacterial infection (SBI). We aimed to correlate...