Bacterial Infections In Febrile Children Research Articles

Evaluation of a Novel Point-of-Care Blood Myxovirus Resistance Protein A Measurement for the Detection of Viral Infection at the Pediatric Emergency Department.

Prompt differentiation of viral from bacterial infections in febrile children is pivotal in reducing antibiotic overuse. Myxovirus resistance protein A (MxA) is a promising viral biomarker. We evaluated the accuracy of a point-of-care (POC) measurement for blood MxA level compared to the reference enzyme immunoassay in 228 febrile children aged between 4 weeks and 16 years, enrolled primarily at the emergency department (ED). Furthermore, we analyzed the ability of MxA to differentiate viral from bacterial infections. The mean difference between POC and reference MxA level was -76 µg/L (95% limits of agreement from -409 to 257 µg/L). Using a cutoff of 200 µg/L, POC results were uniform with the reference assay in 199 (87.3%) children. In ED-collected samples, the median POC MxA levels (interquartile range) were 571 [240-955] µg/L in children with viral infections, 555 (103-889) µg/L in children with viral-bacterial co-infections, and 25 (25-54) µg/L in children with bacterial infections (P < 0.001). MxA cutoff of 101 µg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. POC MxA measurement demonstrated acceptable analytical accuracy compared to the reference method, and good diagnostic accuracy as a biomarker for viral infections.

Clinical relevance of blood urea nitrogen to serum albumin ratio for predicting bacteremia in very young children with febrile urinary tract infection.

Urinary tract infections (UTIs) are one of the most common bacterial infections in febrile children and a common cause of hospitalization, especially in very young children. We examined the clinical characteristics and predictive factors of concomitant bacteremia in pediatric patients with febrile UTI aged ≤24 months. This retrospective multicenter study reviewed medical data from 2,141 patients from three centers from January 2000 to December 2019. Enrolled cases were classified into the bacteremic UTI and non-bacteremic UTI groups according to the presence of blood culture pathogens. Among 2,141 patients with febrile UTI, 40 (1.9%) had concomitant bacteremia. All patients in the bacterial group were aged ≤6 months. Multivariate analysis revealed that younger age, lower blood lymphocyte counts and serum albumin levels, higher C-reactive protein (CRP) levels, blood urea nitrogen (BUN) levels, and BUN/serum albumin ratio were independent risk factors of concomitant bacteremia. The area under the receiver-operating characteristic curves predicting bacteremia were 0.668 for CRP, 0.673 for lymphocytes, and 0.759 for the BUN/albumin ratio. The present study identified the BUN/albumin ratio and lower blood lymphocyte counts as novel predictive factors for bacteremia in young infants with febrile UTI in addition to the previously identified factors of younger age and higher CRP levels. Our findings could help to identify patients at high risk of bacteremia and benefit decision-making in the management of infants with febrile UTI.

Heart rate and respiratory rate in predicting risk of serious bacterial infection in febrile children given antipyretics: prospective observational study

Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test. Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge.What is Known:• Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs.• The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness.What is New:• Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.

Evaluation of CRP as a marker for bacterial infection and malaria in febrile children at the Douala Gyneco-Obstetric and Pediatric Hospital.

C reactive protein (CRP), a marker for the presence of inflammation, has been extensively studied for distinguishing bacterial from non-bacterial infection in febrile patients, but its role in excluding malaria in the febrile child has not been thoroughly evaluated. This was a cross-sectional study at the Douala Gyneco-Obstetric and Pediatric Hospital which included all patients between the ages of one month and 16 years presenting with fever. Consenting patients received complete clinical examinations, then venous blood samples were collected and tested for CRP values, bacterial infection and malaria. Samples of 220 children were analyzed. 142/220 had viral infections, 50/220 had malaria and 49/220 had bacterial infections. 7/220 had both malaria and bacterial infection. There was no significant difference between mean CRP values in malaria and bacterial infection (p = 1), but CRP means were significantly higher in malaria/bacterial infection than in viral infection (p<0.0001). Area Under the Receiver Operating Characteristics Curve (AUROC) values were 0.94 for malaria and 0.86 for bacterial infection, with a calculated cut-off of 23.6mg/L for malaria and 36.2mg/L for bacterial infection. At these cut-offs, CRP had a Positive Predictive Value (PPV) of 68.75% and 85.00% for malaria and bacterial infection respectively, with a Negative Predictive Value (NPV) of 94.74% and 89.05% respectively. CRP can effectively exclude malaria and bacterial infection in febrile children in low-resource settings without the need for additional tests.

Evaluation of CRP as a Marker for Malaria and Bacterial Infection in Febrile Children at Douala Gyneco-Obstetric and Pediatric Hospital

Evaluation of CRP as a Marker for Malaria and Bacterial Infection in Febrile Children at Douala Gyneco-Obstetric and Pediatric Hospital

Novel Biomarkers Differentiating Viral from Bacterial Infection in Febrile Children: Future Perspectives for Management in Clinical Praxis.

Differentiating viral from bacterial infections in febrile children is challenging and often leads to an unnecessary use of antibiotics. There is a great need for more accurate diagnostic tools. New molecular methods have improved the particular diagnostics of viral respiratory tract infections, but defining etiology can still be challenging, as certain viruses are frequently detected in asymptomatic children. For the detection of bacterial infections, time consuming cultures with limited sensitivity are still the gold standard. As a response to infection, the immune system elicits a cascade of events, which aims to eliminate the invading pathogen. Recent studies have focused on these host–pathogen interactions to identify pathogen-specific biomarkers (gene expression profiles), or “pathogen signatures”, as potential future diagnostic tools. Other studies have assessed combinations of traditional bacterial and viral biomarkers (C-reactive protein, interleukins, myxovirus resistance protein A, procalcitonin, tumor necrosis factor-related apoptosis-inducing ligand) to establish etiology. In this review we discuss the performance of such novel diagnostics and their potential role in clinical praxis. In conclusion, there are several promising novel biomarkers in the pipeline, but well-designed randomized controlled trials are needed to evaluate the safety of using these novel biomarkers to guide clinical decisions.

A Case Series of Kawasaki Disease in Children With Sickle Cell Disease.

Prompt recognition and treatment of presumed bacterial infection in febrile children with sickle cell disease is necessary due to splenic dysfunction and impaired immune response. However, fever may be a manifestation of a noninfectious process, and health care providers must consider alternative sources. We describe 2 cases of children with sickle cell disease and persistent fevers, ultimately diagnosed with Kawasaki disease. These cases provide examples of an acute febrile illness that could lead to serious consequences if differential diagnoses are not considered and treatment is delayed.

Incidence and predictors of bacterial infections in febrile children with sickle cell disease.

IntroductionSickle cell disease (SCD) is an autosomal recessive disorder. The incidence of bacterial infection in children with SCD globally is 16% compared 3–14% in general children. Bacterial infection in children is a severe problem and is considered to be a life-threatening condition. To reduce antibiotic overuse, the following factors might be associated with bacterial infection could help: age, C-reactive protein (CRP), white blood cells (WBCs) count, absolute neutrophil count (ANC), and genotype. Therefore, this study is designed to evaluate the CRP, ANC, WBCs, and platelet count levels as predictors for bacterial infection in febrile children with sickle cell anemia over a six-year period in a tertiary center in Jeddah, Saudi Arabia.MethodsThis study was a retrospective record review that included all SCD patients below the age of 18 years who presented with a febrile episode at any hospital’s department from 2017 to 2019. Data were extracted from patient files that included culture result and the causative organism, CRP level, WBCs, ANC, and platelet count.ResultsThe study included 62 children diagnosed with SCD who presented with 89 febrile episodes. There was no statistically significant difference in the median of CRP and ANC between the bacterial and nonbacterial febrile episodes (P = .314, .735, respectively). However, the level of WBC> 20 K/μL was statistically significant at P = .025.ConclusionWBCs significantly associated with a bacterial infection in SCD febrile children along with clinical assessments. This parameter can guide the physicians to determine the children at high risk of bacterial infection.

Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study

ObjectivesTo develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers.DesignProspective observational study.Setting12 emergency departments...

Type I Interferon in Children with Viral or Bacterial Infections.

Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. clinicaltrials.gov (NCT03163628).

Yale observation scale for bacterial infection in febrile children

Background: Sepsis is one of the leading causes of mortality in children under 5 years by UNICEF statistics which is difficult to diagnose because of nonspecific initial clinical presentation and potential for rapid deterioration. In this regard use of Yale Observation Scale assists in early recognition of serious bacterial infection than other laboratory investigation as it is simple, quick, easy to apply and cost-effective bed side scale.Methods: All eligible young febrile infants and children were consecutively enrolled in the study. Axillary temperatures of the cases were documented. Yale observation scoring was done. Blood sample were sent for culture and sensitivity. Colonies were identified morphologically by Gram stain and biochemically. The collected data was analyzed using ROC curve for finding cut off scores of Yale Observation Scale for prediction of severe bacterial illness and final outcome. Statistical analysis was performed using the Statistical Packages for Social Sciences (SPSS) version 14 for MS Window.Results: Bacteremia was found in 23(15.3%) out of total 150 young febrile children enrolled in the present study. It shows that in lower YOS score blood culture was sterile and in higher YOS score blood culture was positive for bacteremia, which is statistically significant with p value (&lt;0.05). As per ROC curve analyses the best cut off value of YOS for prediction of bacteremia was 17.5 with sensitivity 91.3%, specificity 81.9%, PPV 47.7% and NPV of 98.1%.Conclusions: YOS of &gt;17.5 has a good predictive ability for prediction of bacteraemia in young febrile children.

Profile of C-reactive protein, leucocyte and neutrophil populations as predictors of bacterial infections in febrile children

Objective: C-reactive protein, total White Blood Cell count and Absolute Neutrophil counts are important inflammatory markers. These tests are highly significant as predictor of bacterial infection in febrile children. Materials and Methods: We have collected data of 149 samples from pediatric indoor and outdoor patients. Samples were collected in both plain and EDTA vacuette. From plain vacuette CRP test was done and from EDTA vacuette total WBC count and absolute neutrophil count were done. Results: In present study we have collected data of 149 pediatric patient. Total number of patient having bacterial infection were 101. Out of which CRP positive samples were 91(90%), 56(55.4%) samples show leucocytosis and 36(35.6%) samples show neutrophilia. Conclusion: CRP test along with total WBC count and Absolute Neutrophil Count will be helpful for early prediction of bacterial infection and this test will guide clinician for better outcome of febrile children. Keywords: C-reactive protein, Total WBC count, Absolute Neutrophil count, Bacterial infection, Children.

A qPCR expression assay of IFI44L gene differentiates viral from bacterial infections in febrile children

The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10−4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10−5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.

Procalcitonin as an early marker of invasive bacterial infection in febrile children aged 1 month to 5 years of age

Objectives: To evaluate the role of serum procalcitonin as a marker of invasive bacterial infection in febrile children between 1 month to 5 years of age. METHOD: Febrile Children aged between 1 month to 5 years with temperature at admission of ≥ 38 0C (100.4 0F) and with no prior antibiotic use during the current febrile illness were studied prospectively. Results: At a cutoff value of 2 ng/ml for serum PCT levels the sensitivity of 90%, specificity 76%, positive predictability value 78%, negative predictability value of 88%, area under curve (AUC) of 0.935 with standard error of 0.0221 and 95% confidence interval of 0.892 to 0.979 was obtained. The optimum sensitivity and specificity was 86% and 84% respectively at PCT level of ≥ 2.27 ng/ml. Conclusions: Considering this high sensitivity and significant area under curve (AUC) it could be concluded that Serum PCT levels could serve a reliable early biomarker of invasive bacterial infection.

Prevalence of Severe Bacterial Infection in Febrile Children with Sickle CELL Disease in the Era of Pneumococcal Conjugate Vaccine 13

IntroductionThe incidence of invasive pneumococcal infections in patients with sickle cell disease (SCD) decreased after introduction of penicillin prophylaxis and pneumococcal conjugate vaccine (PCV). However, the decrease in pneumococcal infections alone may not necessarily mean an overall decrease in severe bacterial infections (SBI). In a previous publication, we reported a 0.4 % prevalence of pneumococcal bacteremia following introduction of PCV 13. In the current study, we aimed to define the prevalence of SBI and hospitalization in febrile patients in the same cohort in the later years.MethodsWe performed a retrospective study of patients with SCD <18 years old presenting with fever to University of South Alabama Children's and Women's Hospital from January 2014 to June 2017. SBI was defined as: bacteremia, pneumonia, pyelonephritis, meningitis, osteomyelitis and abscess (superficial and deep). Univariate analysis and multivariate logistic regression were used to determine factors associated with patient disposition as well as presence of SBI.ResultsThere were 258 febrile events in 120 patients resulting in 187 (72%) admissions (figure 1). SBI was seen in 12% of admissions with uncomplicated community acquired pneumonia being the most common. The prevalence of bacteremia was 1.6% with single cases of pneumococcus, E. coli, and H. influenzae bacteremia. Younger age, high fever, and splenectomy were associated with hospitalization (p<0.05). However, only C reactive protein was associated with SBI (p<0.02). Viral infection was diagnosed in 80% of outpatients but 87% were given antibiotics. Among inpatients, all received parenteral antibiotics, and 67% were assessed to have viral illness, although only 23% had a virus identified. Pneumococcal vaccination status was satisfactory in 77% of our sample while compliance rate with penicillin prophylaxis was >85% in both inpatient and outpatient groups.ConclusionAlthough majority of febrile events were due to viral infections, 3 of four febrile episodes in our cohort resulted in hospitalization. A small proportion of patients had SBI and a much smaller proportion had bacteremia. These findings support early virus identification which can have implications on patient discharge disposition and antibiotic use. Further studies looking at risk stratification of febrile patients with SCD are needed to encourage outpatient management without compromising safety. [Display omitted] DisclosuresImran:Novo Nordask: Speakers Bureau.

Can clinical signs or symptoms combined with basic hematology data be used to predict the presence of bacterial infections in febrile children under - 5\u2009years?

BackgroundInfectious diseases in children living in resource-limited settings are often presumptively managed on the basis of clinical signs and symptoms. Malaria is an exception. However, the interpretation of clinical signs and symptoms in relation to bacterial infections is often challenging, which may lead to an over prescription of antibiotics when a malaria infection is excluded. The present study aims to determine the association between clinical signs and symptoms and basic hematology data, with laboratory confirmed bacterial infections.MethodsA health survey was done by study nurses to collect clinical signs/symptoms in febrile (axillary temperature ≥ 37.5 °C) children under - 5 years of age. In addition, blood, stool and urine specimen were systematically collected from each child to perform bacterial culture and full blood cell counts. To determine the association between a bacterial infection with clinical signs/symptoms, and if possible supported by basic hematology data (hemoglobin and leucocyte rates), a univariate analysis was done. This was followed by a multivariate analysis only on those variables with a p-value p < 0.1 in the univariate analysis. Only a p-value of < 0.05 was considered as significant for multivariate analysis.ResultsIn total, 1099 febrile children were included. Bacteria were isolated from clinical specimens (blood-, stool- and urine- culture) of 127 (11.6%) febrile children. Multivariate logistical regression analysis revealed that a general bacterial infection (irrespective of the site of infection) was significantly associated with the following clinical signs/symptoms: diarrhea (p = 0.003), edema (p = 0.010) and convulsion (p = 0.021). Bacterial bloodstream infection was significantly associated with fever> 39.5 °C (p = 0.002), diarrhea (p = 0.019) and edema (p = 0.017). There was no association found between bacterial infections and basic haematological findings. If diarrhea and edema were absent, a good negative predictive value (100%) of a bacterial bloodstream infection was found, but the positive predictive value was low (33.3%) and the confidence interval was very large (2.5–100; 7.5–70.1).ConclusionOur study demonstrates that clinical signs and symptoms, combined with basic hematology data only, cannot predict bacterial infections in febrile children under - 5 years of age. The development of practical and easy deployable diagnostic tools to diagnose bacterial infections remains a priority.

The clinical value of plasma hepcidin levels in predicting bacterial infections in febrile children

Febrile children are often evaluated for the risk of bacterial infections in the pediatric emergency department (PER). Hepcidin is an acute phase inflammatory protein. In this study, we examined the plasma hepcidin levels in febrile children. This study was conducted at a pediatric emergency department with 123 febrile children. We measured plasma hepcidin levels using an enzyme-linked immunosorbent assay. We further evaluated clinical characteristics and routine blood tests along with the hepcidin levels. We observed significantly higher plasma hepcidin levels in bacterial enteritis (p=0.026) and combined with urinary tract infection (p=0.007). Furthermore, hepcidin levels had a significantly positive correlation with CRP level and length of hospital stay (R=0.296, p=0.001 and R=0.213, p=0.018). Hepcidin levels greater than 65ng/mL also more accurately predicted bacterial infections than values below 65ng/mL (11.7% vs. 2.1%, Odds ratio 8.4, 95% confident interval 1.7-40.9, p=0.002). This study provides evidence that febrile children with bacterial infection have higher plasma hepcidin levels, and the values correlated with CRP level and length of hospital stay. Therefore, hepcidin values can potentially be adopted as a biomarker for identifying febrile children with bacterial infection, particularly bacterial enteritis and urinary tract infection.

Clinical prediction models for young febrile infants at the emergency department: an international validation study

ObjectiveTo assess the diagnostic value of existing clinical prediction models (CPM; ie, statistically derived) in febrile young infants at risk for serious bacterial infections.MethodsA systematic literature review identified eight CPMs...

C-reactive Protein as a Diagnostic Marker of Bacterial Infection in Febrile Children

C-reactive Protein as a Diagnostic Marker of Bacterial Infection in Febrile Children

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.