Development and evaluation of a mortality risk prediction model for severe bacterial infections in children / 中华急诊医学杂志

Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.

Utilidad de los parámetros clínicos y de laboratorio básicos para predecir infección bacteriana seria en menores de 3 meses que se hospitalizan por síndrome febril sin foco / 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

Resumen: Introducción: Un 20% de los niños con síndrome febril se presenta como síndrome febril sin foco (SFSF). Las es trategias de manejo en este grupo presentan alta sensibilidad, pero baja especificidad. Objetivos: Ca racterizar las infecciones bacterianas serias (IBS) en menores de 3 meses hospitalizados por SFSF, y evaluar utilidad de parámetros clínicos y de laboratorio en la identificación de pacientes con alto riesgo de IBS. Pacientes y Método: Estudio prospectivo en pacientes < 3 meses hospitalizados entre enero 2014 y noviembre 2015 por SFSF en dos hospitales pediátricos de la Región Metropolitana. Criterios de inclusión: edad 4 días - 3 meses, fiebre > 38°C de < 72 h de evolución sin causa demostra ble. Criterios de exclusión: uso de antimicrobianos hasta 7 días previo a su ingreso, prematuros < 34 semanas, peso de nacimiento < 2 kg e inmunocomprometidos. Se registraron datos demográficos, clínicos, y exámenes de laboratorio, hemograma y PCR, diagnóstico de egreso, IBS descartada, IBS probable o confirmada. Resultados: 32% de los pacientes egresó con diagnóstico de IBS, 28% con diagnóstico de infección viral o probablemente viral, 34% con diagnóstico de SFSF no especificado y 6% SFSF por otras causas. No se encontraron diferencias significativas en PCR, leucocitosis, aspecto tóxico ni horas de fiebre al ingreso al comparar los grupos con y sin IBS (p > 0,05). La combinación de parámetros clínicos y de laboratorio mostro sensibilidad de 27%, especificidad de 90%, VPP 60% y VPN 71%. Conclusión: No fue posible establecer que parámetros clínicos y de laboratorio permitan identificar menores de 3 meses con alto riesgo de IBS, manteniendo su utilidad como indicadores de bajo riesgo. Es necesario contar con otros elementos clínicos y de laboratorio que permitan discrimi nar IBS de infecciones virales.

Abstract: Introduction: 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. Objectives: 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. Patients and Method: 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. Inclusion criteria: age 4 days - 3 months, fever > 38°C longer than 72 hours after onset without demonstrable cause. Exclusion criteria: 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. Results: 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. Conclusion: 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.

Incidence of reactive thrombocytosis in serious bacterial infections in children aged two months to twelve years and its usefulness as a predictor of serious bacterial infections

Background: The aims of the study were to estimate the incidence of reactive thrombocytosis(RT) among febrile children aged 2 months to 12 years and to identify any differences in age group and gender in mounting thrombocytosis as a response to infection, to identify if thrombocytosis occurred preferentially in any particular group of serious bacterial infections(SBI), to compare thrombocytosis with other parameters like total white cell count, C-reactive protein(CRP), cultures etc. and to assess the utility of platelet count as a potential predictor of serious bacterial infection.Methods: This was a prospective study done in Institute of Child Health and Hospital for children, Madras Medical College from September 2015 to July 2016. Inclusion criteria: Children aged 2 months to 12 years with symptoms of fever less than 6 days admitted in the paediatric wards and those seen at the outpatient department. Exclusion criteria: Children having received parenteral antibiotics.Results: Of the 500 children, 142 (28.4%) had reactive thrombocytosis. RT was mild in 120 children (24%), moderate in 16 children (3.2%), severe in 4(0.8%) and extreme in two children (0.4%). This study showed that 36.48% (85 / 233) of children under 1 year had RT (p = 0.0002).There was no significant sex related difference in mounting RT. Out of 500 children included in the study, serious bacterial infection was diagnosed among 171 children (34.2%).Pneumonia (n=100) was the most common SBI followed by urinary tract infections (n=33), meningitis (n=23), sepsis (n=15). This study showed that RT has a moderate ability to predict serious bacterial infections (AUC=0.78; PPV-75.35%).Conclusions: Incidence of reactive thrombocytosis in febrile children aged 2 months to 12 years is 28.4%. It occurs more frequently in infants and without any sex predilection. RT is associated with leucocytosis, positive CRP, positive Chest X ray findings, positive urine culture and positive CSF findings. This shows that RT has a moderate ability in predicting SBI in children.

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 (<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 '>17.5 has a good predictive ability for prediction of bacteraemia in young febrile children.

Un modelo de predicción de meningitis bacteriana en recién nacidos con pleocitosis del líquido cefalorraquídeo / A bacterial meningitis predictive model for newborns with cerebrospinal fluid pleocytosis

Introducción: se han desarrollado herramientas de predicción de meningitis bacteriana (MB) en pacientes pediátricos, pero ellas no incluyen el período neonatal. Objetivo: diseñar y validar un modelo de predicción de MB en pacientes neonatales quienes presentan pleocitosis del líquido cefalorraquídeo (LCR) al ser evaluados por variables clínicas y de laboratorio. Pacientes y método: estudio retrospectivo y analítico, que incluyó 320 pacientes neonatales evaluados por probable infección, en quienes se hizo el diagnóstico de meningitis, 45 con MB y 275 con meningitis aséptica, e ingresados en el Servicio de Neonatología del Hospital Pediátrico Universitario Juan M. Márquez, entre Febrero de 1992 y Diciembre del 2009. Se creó un Modelo Predictivo de Meningitis Bacteriana, sobre la base de un conjunto de variables identificadas mediante procedimientos de análisis uni y multivariado. El modelo se diseñó a partir de una población de derivación y se contrastó en otro grupo, este de validación. Resultados: las variables seleccionadas para integrar el modelo predictivo fueron: 1) Apariencia de estado tóxico-infeccioso, 2) Convulsiones en el transcurso de la enfermedad, 3) Tinción de Gram del LCR positiva, 4) Proporción de leucocitos polimorfonucleares en el LCR >80 por ciento, y 5) Glucorraquia <1.0 mMol/l. Con estas variables se alcanzaron sensibilidad y valor predictivo negativo de 100.0 por ciento. Con el modelo propuesto, en el grupo de derivación no hubo ningún paciente malclasificado con predicción negativa de MB pero portador de este tipo de infección. En el grupo de validación, el modelo tuvo un desempeño similar, lo cual lo acredita como un modelo de predicción validado internamente. Conclusiones: el modelo de predicción diseñado descansa en variables de evaluación rutinarias, y permitió identificar inequívocamente la totalidad de los pacientes neonatales con MB. Su empleo podría ser una herramienta útil en la toma de decisiones clínicas

Introduction: there were developed a prediction tools for bacterial meningitis (BM) in pediatric patients, but those do not include the neonatal period. Objetive: to develop and validate a prediction model for BM in neonatal patients who present pleocytosis of the cerebrospinal fluid (CF) when they were evaluated by clinical and laboratory variables. Patients and method: retrospective and analytic study, which included 320 neonatal patients evaluated for probable infection, with the diagnosis of meningitis, 45 with BM and 275 with aseptic meningitis, and who were admitted in the Neonatology Ward at the Universitary Pediatric Hospital Juan M. Márquez, from february of 1992 up to december of 2009. There was developed a Predictive Model for BM, owing to some variables identified in uni and multivariate analysis. This model was developed from a derivation group and it was contrasted in the validation group. Results: the variables selected to be included at the predictive model were: 1) Toxic appearance, 2) Seizures in the course of the illness, 3) positive CF Gram stain, 4) Polymorphonuclear leukocytes proportion in CF >80 percent , and 5) CF glucose concentration <1.0 mMol/l. The values for the variables as a whole revealed to have 100.0 percent sensitivity and negative predictive values. With this proposed model there were not any patient misclassified with negative prediction for BM, who result bearer of this kind of infection, in the derivation group. In the validation group the model had a similar performance, which accredit it like an internally validate model. Conclusions: the prediction model developed rest on rutinary evaluation variables, and it allowed to identify without errors all neonatal patients with BM. The ejecution of this model would be an usefull tool in the clinical decisions making

Usefulness of Low-Risk Criteria for Serious Bacterial Infections in Febrile Infants Younger than 90 Days of Age

PURPOSE: To examine the usefulness of simple and quick criteria for identifying febrile infants younger than 90 days with a low risk for serious bacterial infection (SBI). METHODS: We conducted a retrospective study of febrile infants younger than 90 days who visited an emergency department (ED) between July 2010 and June 2011. We reviewed their medical history, physical examination findings, levels of white blood cells (WBC) and C-reactive protein (CRP), blood culture, urinalysis, and an analysis of their cerebrospinal fluid (CSF). Patients who met all the following criteria were considered to have a low risk for SBI: (1) an unremarkable medical history, (2) a good appearance, (3) no focal physical signs of infection, (4) WBC 5,000~15,000 /mm3, (5) CRP <2.0 mg/dL, (6) a normal urinalysis, and (7) CSF WBC <25 /mm3 for neonate or <10 /mm3 for infants between 29 days and 90 days. SBI was defined as a positive culture of bacteria from blood, cerebrospinal fluid, or urine. RESULTS: Complete data were available for 493 infants. SBI was documented in 62(12.6%) infants, with 54(11.0%) having a urinary tract infection, 3(0.6%) with bacteremia, 1 (0.2%) with bacterial meningitis, and 4(0.8%) with co-infections. The sensitivity and negative predictive value for SBI from the combination of low-risk criteria was 98.4% and 99.6%, respectively. CONCLUSION: Although low-risk infants must be carefully observed, our criteria for low-risk might be a reliable and useful tool for excluding SBI for febrile young infants in ED.

Reactive Thrombocytosis in Febrile Young Infants with Serious Bacterial Infection.

Objective: To estimate the incidence of reactive thrombocytosis among febrile young infants and to asses the utility of platelet count as a potential predictor of serious bacterial infection (SBI). Design: Retrospective study between January 2005 and December 2008. Setting: Tertiary care pediatric unit. Participants: All infants 29 to 89 days of age, admitted with rectal temperature >38oC without a focus of infection. Main Outcome Measures: The results of the sepsis evaluation on admission were recorded. SBI included all cases of occult bacteremia, urinary tract infection, bacterial meningitis, pneumonia, bacterial gastroenteritis and infections of the soft tissues and bones. Results: Of the 408 infants studied, 103 (25.2%) had SBI. Platelet count was significantly higher in infants with SBI compared to those without (median 513000 /mm3 [interquartile range 455,000–598,000/mm3] vs median 398000/mm3; [interquartile range 313,000–463,000/ mm3]; P<0.001). Thrombocytosis had only moderate ability in predicting SBI (area under the curve: 0.74, 95%CI 0.70-0.79). The combination of platelet count ≥450,000/ mm3, WBC ≥15,000/mm3, C-reactive protein ≥2 mg/dL, and pyuria ≥10 WBC/hpf would lead to misclassification of 4 infants with SBI (3.9% of SBIs; negative likelihood ratio 0.08). Conclusions: Reactive thrombocytosis was a frequent finding in young infants with SBI. Thrombocytosis ≥450,000 cells/mm3, in combination with leucocytosis, elevated CRP and pyuria, may help in early recognition of febrile young infants at risk for SBI.

Febre sem sinais localizatórios: avaliação de um protocolo de atendimento / Fever without source: evaluation of a guideline

OBJETIVO: Avaliar a aplicabilidade de um protocolo de atendimento padronizado para crianças de até 36 meses de idade com febre sem sinais localizatórios (FSSL). MÉTODOS: Estudo de coorte prospectivo em crianças com FSSL atendidas no Pronto-Socorro do Hospital Universitário da Universidade de São Paulo, São Paulo (SP), de junho de 2006 a maio de 2007. O protocolo estratifica o risco de infecção bacteriana grave (IBG) de acordo com a presença ou não de toxemia, idade e valor da temperatura. Conforme avaliação de risco, indicava-se triagem laboratorial: hemograma, hemocultura, sedimento urinário, urocultura e, se necessário, radiografia torácica, liquor e coprocultura. RESULTADOS: Foram estudadas 251 crianças das quais 215 foram acompanhadas até o diagnóstico final. Vinte crianças apresentavam toxemia, e 195 estavam em bom estado geral (30 com idade de até 3 meses, e 165, de 3 a 36 meses). Nas crianças de 3 a 36 meses não toxêmicas, 95 tinham temperatura axilar > 39 ºC. Em 107 crianças (49,8 por cento), houve melhora espontânea do quadro febril; em 88 (40,9 por cento), foi identificada doença benigna autolimitada; e em 20 (9,3 por cento), IBG. Dentre as IBG, identificamos 16 infecções urinárias, três pneumonias e uma bacteremia oculta. Das 215, 129 (60 por cento) não receberam qualquer antibioticoterapia, e 86 receberam antibiótico em algum momento (45, empiricamente). O antibiótico empírico foi mantido por, em média, 72 horas. CONCLUSÃO: O protocolo aplicado mostrou-se adequado para o seguimento destas crianças que fizeram coleta de exames simples e passíveis de serem realizados na maioria dos serviços. A infecção urinária foi a IBG mais frequente nas crianças com FSSL.

OBJECTIVE: To evaluate the applicability of a standardized guideline for children up to 36 months of age with fever without source (FWS). METHODS: Prospective cohort study involving children with FWS treated at the emergency department of Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil, from June 2006 to May 2007. The guideline classifies the risk of serious bacterial infection (SBI) according to the presence or absence of toxemia, age, and temperature. Laboratory screening was based on risk assessment: complete blood count, blood culture, urinalysis, urine culture, and, if necessary, chest radiography, cerebrospinal fluid, and coproculture. RESULTS: We studied 251 children and, of these, 215 were followed up until the final diagnosis. Toxemia was found in 20 children, and 195 were well-appearing (30 up to 3 months old and 165 from 3 to 36 months old). Among those children from 3 to 36 months without toxemia, 95 had axillary temperature > 39 ºC. In 107 (49.8 percent) children, there was spontaneous resolution of fever; in 88 (40.9 percent), benign self-limited disease was identified; and in 20 (9.3 percent), there was SBI. Among the cases of SBI, we identified 16 urinary tract infections, three cases of pneumonia and one occult bacteremia. Of the 215 children, 129 (60 percent) received no antibiotics, and 86 received antibiotics at some point (45 empirically). Empirical antibiotic treatment was maintained for an average of 72 hours. CONCLUSION: The guideline was shown to be appropriate to follow up these children using simple laboratory tests that can be carried out at most health facilities. The most frequent SBI in this sample was urinary tract infection.

Risk Factors for Serious Bacterial Infection in Febrile Young Infants in a Community Referral Hospital

Differentiation of serious bacterial infection (SBI) from self-limiting viral illness in febrile infants younger than three months is a significant challenge for clinicians. We aimed to assess the risk factors for SBI in febrile infants. Data were obtained from 221 infants younger than three months who visited a single community referral hospital for fever and underwent a complete sepsis workup between August 2003 and July 2006. The causes of fever were febrile illness without a documented cause (FISDC, 65%), urinary tract infection (UTI, 12%), aseptic meningitis (12%), bacteremia (4%), bacterial meningitis (2%). Cerebrospinal fluid enterovirus polymerase chain reaction was positive in 28% of FISDC and 48% of aseptic meningitis cases. When UTI was excluded, the risk factors for SBI were 1) C-reactive protein (CRP) level of > or =1.87 mg/dL and 2) fevers of > or =38.9degrees C. The specificity and negative predictive values of risk factors 1) and 2) for the diagnosis of SBI were 94% and 95%, respectively. We concluded that enteroviral infection may be a major cause of febrile episodes in infants younger than three months. If UTI could be excluded, the presence of CRP levels > or =1.87 mg/dL and fevers of > or =38.9degrees C can be used as criteria to rule out SBI in these infants.

Predictors of Clinically Non Specific Bacterial Infection in Febrile Children Less than 3 Years of Age: WBC, ESR and CRP

PURPOSE: Our examination was designed to determine the diagnostic properties of the cutoff point for the prediction of bacteremia in febrile children less than 3 years of age. Cutoff point is the value that simultaneously maximizes both sensitivity and specificity. METHODS: We conducted a retrospective study of febrile children, less than 3 years of age, who clinically have no identifiable source of fever. Peripheral blood leukocyte count(WBC), absolute neutrophil count(ANC), erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) were measured at the same time. All patients received blood culture, urine culture and/or CSF culture. Bacterial infection was defined as single pathogen isolated from the CSF or blood or a urinary tract infection (UTI). Patients were dichotomized into two groups: those with bacterial infection and no bacterial infection. We analyzed the characteristics of the children in the two groups. RESULTS: Seventy-one patients(44 males; 27 females) were enrolled in the study. Twenty patients (28%) had a serious bacterial infection(twelve urinary tract infection, five bacteremia, three meningitis) and fifty-one(72%) had no serious bacterial infection. WBC, ESR and CRP were significantly different between the two groups(P<0.05). The cutoff point of WBC, ESR and CRP were 20,000/mm3, 30 mm/hr and 3.0 mg/dL, respectively. The sensitivity and specificity of each cutoff point were WBC(75%, 75%), ESR(79%, 68%) and CRP(83%, 77%), respectively. CONCLUSION: These data show the ability of predictors to identify febrile children less than 3 years of age with bacterial infection. Febrile children who reach the cutoff point must be treated intensively and those who do not reach the cutoff point can be carefully managed without administering antimicrobial agents.

Usefulness of Low Risk Criteria for Serious Bacterial Infection Among Febrile Infants Younger than Three Months of Age

PURPOSE: A retrospective study was undertaken to evaluate the usefulness of low risk criteria for identifying febrile infants younger than three months unlikely to have serious bacterial infection. METHODS: We conducted a retrospective study of 527 infants younger than three month with a axillary temperature >or=37.4degrees C. If they met the following all four criteria, appear well, WBC 5,000-20,000/mm3, urine stick WBC(-) and nitrite(-), CSF WBC <10/mm3, they were considered at low risk for serious bacterial infection(SBI). SBI was defined as a positive culture of urine, blood, or cerebrospinal fluid. The sensitivity, specificity, negative predictive value and positive predictive value of the low risk criteria were calculated. RESULTS: Of 527 febrile infants, 110(21.0%) had serious bacterial infections. The 2.7% who met the low risk criteria had SBI and negative predictive value was 97.3%. SBI was diagnosed in 103 infants(38.6%) who didn't meet the low risk criteria including urinary tract infection(78.6%), most commonly, bacteremia(16.5%), bacterial meningitis(8.7%), Salmonella gastroenteritis(1%), osteomyelitis(1%), septic arthritis of hip joint(1%). There were no differences in the sensitivity and negative predictive value according to the monthly-age-group. CONCLUSION: This low risk criteria to identify infants unlikely to have SBI early is available, however low risk infants must be carefully observed.