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OBJECTIVE: To determine features that distinguish febrile young infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: Retrospective single-center study included febrile infants <57 days of age evaluated in the emergency department of Cohen Children's Medical Center of Northwell Health, New Hyde Park, New York, from March 1 to April 30 of 2018, 2019, and 2020. Sociodemographic and clinical features were compared between those seen during the 2020 coronavirus disease-2019 pandemic and previous years, as well as between infants with SARS-CoV-2 infection and infants without SARS-CoV-2 infection (SARS-CoV-2 negative or evaluated during 2018 and 2019). RESULTS: In all, 124 febrile infants <57 days of age were identified; 38 during the 2-month study period in 2018, 33 in 2019, and 53 in 2020. During 2020, fewer febrile infants had a serious bacterial infection or a positive respiratory viral panel than in prior years (6% vs 21% [P = .02]; 15% vs 53% [P < .001], respectively). SARS-CoV-2 was the most frequent pathogen detected in 2020; of 30 infants tested, 20 tested positive. Infants with SARS-CoV-2 were more likely to identify as Hispanic (P = .004), have public insurance or be uninsured (P = .01), exhibited lethargy (P = .02), had feeding difficulties (P = .002), and had lower white blood cell (P = .001), neutrophil (P < .001), and lymphocyte counts (P = .005) than the 81 infants without SARS-CoV-2 infection. None of the infants with SARS-CoV-2 had concurrent serious bacterial infection or detection of another virus. Overall, disease in infants with SARS-CoV-2 was mild. CONCLUSIONS: During the peak of the pandemic, SARS-CoV-2 was the predominant pathogen among febrile infants. Socioeconomic, historical, and laboratory features differed significantly between infants infected or not infected with SARS-CoV-2. None of the 20 infants with SARS-CoV-2 infection had an identified coviral or serious bacterial infection.

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OBJECTIVE: To assess the prevalence of serious infections and mortality among infants ≤90 days of age presenting to the emergency department with hypothermia. STUDY DESIGN: We performed a cross-sectional cohort study of infants ≤90 days presenting to any of 40 EDs in the Pediatric Health Information Systems between January 1, 2009, and December 31, 2018. Infants with an International Classification of Diseases, ninth or tenth edition, admission/discharge diagnosis code of hypothermia were included. We determined the prevalence of serious bacterial infection (urinary tract infection, bacteremia, and/or bacterial meningitis), pneumonia, herpes simplex virus (HSV) infection, and emergency department/hospital mortality. RESULTS: We included 3565 infants (1633 male [50.9%] and 3225 ≤30 days of age [90.5%]). Most (65.0%) presented in the first week of life. There were 389 infants (10.8%) with a complex chronic condition. The prevalence of serious bacterial infection was 8.0% (n = 284), including 2.4% (n = 87) with urinary tract infection, 5.6% (n = 199) with bacteremia, and 0.3% (n = 11) with bacterial meningitis. There were 7 patients (0.2%) with neonatal HSV and 9 (0.3%) with pneumonia; 0.2% (n = 6) died. The presence of a complex chronic condition was associated with the presence of serious bacterial infection (P < .001) and was present in 3 of 6 patients who died. In a sensitivity analysis including patients with any diagnosis code of hypothermia (n = 8122), 14.9% had serious bacterial infection, 0.6% had HSV, and 3.3% had pneumonia; 2.0% died. CONCLUSIONS: Of infants with hypothermia ≤90 days of age, 8.3% had serious bacterial infections or HSV. Compared with literature from febrile infants, hypothermia is associated with a high mortality rate. Complex chronic conditions were particularly associated with poor outcomes. Additional research is required to risk stratify young infants with hypothermia.

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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.

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OBJECTIVE: To determine the risk of bacterial meningitis in infants aged 29-90 days with evidence of urinary tract infection (UTI). METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were systematically searched for studies reporting rates of meningitis in infants aged 29-90 days with abnormal urinalysis or urine culture. Observational studies in infants with evidence of UTI who underwent lumbar puncture (LP) reporting age-specific event rates of bacterial meningitis and sterile cerebrospinal fluid pleocytosis were included. Prevalence estimates for bacterial meningitis in infants with UTI were pooled in a random effects meta-analysis. RESULTS: Three prospective and 17 retrospective cohort studies were included in the meta-analysis. The pooled prevalence of concomitant bacterial meningitis in infants with UTI was 0.25% (95% CI, 0.09%-0.70%). Rates of sterile pleocytosis ranged from 0% to 29%. Variation in study methods precluded calculation of a pooled estimate for sterile pleocytosis. In most studies, the decision to perform a LP was up to the provider, introducing selection bias into the prevalence estimate. CONCLUSIONS: The risk of bacterial meningitis in infants aged 29-90 days with evidence of UTI is low. A selective approach to LP in infants identified as low risk for meningitis by other clinical criteria may be indicated.

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OBJECTIVE: To compare the risk of serious bacterial infection between infants aged ≤60 days who are febrile in the emergency department (ED) and those who have only a history of fever and are afebrile on arrival to the ED. STUDY DESIGN: In this secondary analysis of a multicenter prospective study using data collected between December 2008 and May 2013, we compared the rate of serious bacterial infection (urinary tract infection [UTI], bacteremia, and/or bacterial meningitis) between infants who have a history of fever but are afebrile on arrival to the ED and those with fever documented in the ED (rectal temperature ≥38.0 °C) using relative risk (RR) with 95% CI. Stratified analyses were performed for age (≤28 and 29-60 days) and serious bacterial infection type. Infants born prematurely and those with a clinical focal infection or serious illness were excluded. RESULTS: A total of 3825 infants (mean age, 35.2 days; 56.9% male) were included. Of the 1233 (32.2%) who were afebrile in the ED, 108 (8.8%) had a serious bacterial infection (UTI, n = 94 [7.6%]; bacteremia, n = 19 [1.5%]; bacterial meningitis, n = 8 [0.6%]). Of the 2592 infants (67.8%) who were febrile in the ED, 331 (12.8%) had a serious bacterial infection (UTI, n = 285 [11.0%]; bacteremia, n = 61 [2.4%]; bacterial meningitis, n = 17 [0.7%]). The RR for serious bacterial infection for afebrile vs febrile infants was 0.68 (95% CI, 0.56-0.84). A lower risk of serious bacterial infection was also seen among afebrile vs febrile infants aged ≤28 days (RR, 0.69; 95% CI, 0.52-0.93) and age 29-60 days (RR, 0.67; 95% CI, 0.50-0.89). CONCLUSIONS: The prevalence of serious bacterial infection is lower in infants aged ≤60 days with a history of fever compared with those who are febrile on arrival to the ED. The small risk reduction in this group is unlikely to alter decision making.

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OBJECTIVE: To determine the risk of serious bacterial infections (SBIs) in young febrile infants with and without viral infections. STUDY DESIGN: Planned secondary analyses of a prospective observational study of febrile infants 60 days of age or younger evaluated at 1 of 26 emergency departments who did not have clinical sepsis or an identifiable site of bacterial infection. We compared patient demographics, clinical, and laboratory findings, and prevalence of SBIs between virus-positive and virus-negative infants. RESULTS: Of the 4778 enrolled infants, 2945 (61.6%) had viral testing performed, of whom 1200 (48.1%) were virus positive; 44 of the 1200 had SBIs (3.7%; 95% CI, 2.7%-4.9%). Of the 1745 virus-negative infants, 222 had SBIs (12.7%; 95% CI, 11.2%-14.4%). Rates of specific SBIs in the virus-positive group vs the virus-negative group were: UTIs (33 of 1200 [2.8%; 95% CI, 1.9%-3.8%] vs 186 of 1745 [10.7%; 95% CI, 9.2%-12.2%]) and bacteremia (9 of 1199 [0.8%; 95% CI, 0.3%-1.4%] vs 50 of 1743 [2.9%; 95% CI, 2.1%-3.8%]). The rate of bacterial meningitis tended to be lower in the virus-positive group (0.4%) than in the viral-negative group (0.8%); the difference was not statistically significant. Negative viral status (aOR, 3.2; 95% CI, 2.3-4.6), was significantly associated with SBI in multivariable analysis. CONCLUSIONS: Febrile infants ≤60 days of age with viral infections are at significantly lower, but non-negligible risk for SBIs, including bacteremia and bacterial meningitis.

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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(AU)

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(AU)

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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

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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.

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