Fever Without Source in Children 0 to 36 Months of Age

Estudios recientes han demostrado cambios en la etiología de las infecciones bacterianas potencialmente graves en lactantes menores de 3 meses de vida con fiebre. El objetivo es describir la microbiología y la evolución de estas infecciones en nuestro entorno.

Subanálisis de un estudio prospectivo y multicéntrico sobre lactantes febriles con menos de 3 meses de edad que consultaron desde el 1 de octubre del 2011 hasta el 30 de septiembre del 2013 en los servicios de urgencias de 19 hospitales infantiles españoles de la Red de investigación de la Sociedad Española de Urgencias de Pediatría/Spanish Pediatric Emergency Research Group (RISeuP/SPERG).

Se incluyó a 3.401 lactantes menores de 91 días de vida con fiebre sin foco. Hubo 896 cultivos positivos: 766 urocultivos (85,5%), 100 hemocultivos (11,2%), 18 cultivos de líquido cefalorraquídeo (2%), 10 coprocultivos y 2 cultivos umbilicales. Fueron diagnosticados de una infección bacteriana potencialmente grave 784 niños (23%), de los cuales 107 (3,1%) tenían una infección invasora.

Escherichia coli (E. coli) fue la bacteria más frecuente de urocultivos (628; 82%), hemocultivos (46; 46%) y cultivos de líquido cefalorraquídeo (7; 38,9%) seguido por Streptococcus agalactiae, que fue aislado en 24 (24%) hemocultivos y 3 (16,7%) cultivos de líquido cefalorraquídeo. Solo hubo 2 infecciones producidas por Listeria monocytogenes. Fallecieron 4 niños y 7 desarrollaron complicaciones graves.

E. coli fue la bacteria más frecuente en urocultivos, hemocultivos y cultivos de líquido cefalorraquídeo de los lactantes con menos de 3 meses de vida y fiebre sin foco, incluso entre los neonatos.

Recent studies have shown changes in the aetiology of serious bacterial infections in febrile infants ≤ 90 days of age. The aim of this study was to describe the current microbiology and outcomes of these infections in Spain.

Sub-analysis of a prospective multicentre study focusing on febrile infants of less than 91 days of life, admitted between October 2011 and September 2013 to Emergency Departments of 19 Spanish hospitals, members of the Spanish Paediatric Emergency Research Group of the Spanish Society of Paediatric Emergencies (RISeuP/SPERG).

The analysis included 3,401 febrile infants ≤90 days of age with fever without source. There were 896 positive cultures: 766 urine (85.5%), 100 blood (11.2%), 18 cerebrospinal fluid (2%), 10 stool, and 2 umbilical cultures. Among the 3,401 infants included, 784 (23%) were diagnosed with a serious bacterial infection, and 107 of them (3.1%) with an invasive infection.

E. coli was the most common pathogen isolated from urine (628; 82%), blood (46; 46%), and cerebrospinal fluid cultures (7; 38.9%), followed by S. agalactiae that was isolated from 24 (24%) blood cultures and 3 (16.7%) cerebrospinal fluid cultures. There were only 2 L. monocytogenes infections. Four children died, and seven had severe complications.

Among infants ≤ 90 days of age with fever without source, E. coli was the most common pathogen isolated from urine, blood, and cerebrospinal fluid cultures.

Very little information exists on simultaneous infections by viruses and bacteria in infants with fever without source (FWS).

To investigate the incidence of bacterial coinfection in infants up to 3 months of age with neurological viral infection.

Prospective study performed in infants below 90 days of age attending the emergency room of two public hospitals in Spain for FWS. Those who had viral screening performed in CSF, together with blood, CSF and urine cultures were included. Herpes virus, EV and HPeV detection in CSF was performed by PCR. Coinfections between viruses in CSF and serious bacterial infections were described.

119 Infants less than 90 days of age were recruited. Forty-five (38%) had viral infection of the central nervous system, and in 8 of them (17.7%) we found a concurrent bacterial infection: 7 urinary tract infections (UTI) and 1 sepsis. In all cases, the virus identified in CSF was EV.

Bacterial infections were frequent in young infants with viral neurological infections associated to EV. Urinary tract infection was the most common bacterial disease.

The objective was to investigate the effect of commonly used inhaled corticosteroids on white blood cell count (WBC) and to examine the mechanisms involved.

This randomized comparative study comprised 60 healthy adults. We measured the effects of budesonide (by face mask inhalation or aerosol inhaler), fluticasone (by inhaler), and saline inhalation (control) on WBC and the differential leukocyte count, especially the absolute neutrophil count (ANC). To elucidate the mechanisms involved, we measured the expression of the adhesion neutrophil ligands Mac-1 (CD11b) and L-selectin (CD62L), and granulocyte colony-stimulating factor serum levels.

Six hours after a single-dose inhalation of budesonide, mean increases of 23.4% in WBC (95% confidence interval [CI], 11.3-35.4) and 30.1% in ANC (95% CI, 7.2-53.0) were noted. The percentage of neutrophils increased from 54.6% to 58.1% (P< .001). Inhaled fluticasone increased WBC and ANC by 12.6% (95% CI, 1.5-23.7) and 22.7% (95% CI, 6.2-39.2), respectively (P< .01 for both). The absolute lymphocyte and eosinophil counts did not change significantly from baseline.

The expression of Mac-1 and L-selectin decreased by 51.0% (P< .01) and 30.9% (P= .02), respectively, following face mask inhalation of budesonide and by 39.8% (P= .01) and 17.4% (P= .17), respectively, following inhalation of fluticasone. No significant changes in granulocyte colony-stimulating factor levels were noted.

Glucocorticoid inhalation increases WBC by increasing ANC. Reduced neutrophil adhesion to the endothelial surface, mediated by decreased adhesion molecule expression on neutrophils, is a plausible mechanism. Physicians should be aware of the effect of inhaled corticosteroids on WBC, as it may influence clinical decisions, especially in the emergency department.

The cause of fever in a child can often be determined from history, physical examination, and laboratory tests; infections account for the majority of cases. Yet in 20%, no apparent cause can be found, designated as fever without source (FWS). The yield of chest radiography in children with FWS is low, and it is usually not appropriate. However, in children with respiratory signs, high fever (>39°C), or marked leukocytosis (≥20,000/mm³), chest radiography is usually appropriate, as it has a higher yield in detecting clinically occult pneumonia. In newborns with FWS, there is higher risk for serious bacterial infection, and the routine use of chest radiography is controversial. In children with neutropenia, fever is a major concern. In some clinical circumstances, such as after hematopoietic stem cell transplantation, chest CT scan may be appropriate even if the results of chest radiography are negative or nonspecific, as it has higher sensitivity and can demonstrate specific findings (such as lung nodule and “halo sign”) that can guide management. In a child with prolonged fever of unknown origin despite extensive medical workup (fever of unknown origin), diagnosis is usually dependent on clinical and laboratory studies, and imaging tests have low yield.

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Accurate measurement of very low cerebrospinal fluid (CSF) white blood cell (WBC) concentration is key to the diagnosis of bacterial meningitis, lethal if not promptly treated. Here we show that high frequency ultrasound (HFUS) can detect CSF WBC in vitro in concentrations relevant to meningitis diagnosis with a much finer precision than gold standard manual counting in a Fuchs-Rosenthal chamber. WBC concentrations in a mock CSF model, in the range 0–50 WBC/μL, have been tested and compared to gold standard ground truth. In this range, excellent agreement (Cohen's kappa [κ] = 0.78–90) (Cohen 1960) was observed between HFUS and the gold standard method. The presented experimental set-up allowed us to detect WBC concentrations as low as 2 cells/μL. HFUS shows promise as a low-cost, reliable and automated technology to measure very low CSF WBC concentrations for the diagnosis of early meningitis.

Febrile illness in children younger than 36 months is common and has potentially serious consequences. With the widespread use of immunizations against Streptococcus pneumoniae and Haemophilus influenzae type b, the epidemiology of bacterial infections causing fever has changed. Although an extensive diagnostic evaluation is still recommended for neonates, lumbar puncture and chest radiography are no longer recommended for older children with fever but no other indications. With an increase in the incidence of urinary tract infections in children, urine testing is important in those with unexplained fever. Signs of a serious bacterial infection include cyanosis, poor peripheral circulation, petechial rash, and inconsolability. Parental and physician concern have also been validated as indications of serious illness. Rapid testing for influenza and other viruses may help reduce the need for more invasive studies. Hospitalization and antibiotics are encouraged for infants and young children who are thought to have a serious bacterial infection. Suggested empiric antibiotics include ampicillin and gentamicin for neonates; ceftriaxone and cefotaxime for young infants; and cefixime, amoxicillin, or azithromycin for older infants.