Javier Benito

Blood culture and bacteremia predictors in infants less than three months of age with fever without source.

Objectives: (1) To assess the rate of bacteremia in febrile infants less than 3 months of age admitted to a pediatric emergency department at a tertiary hospital; (2) to describe the bacteria isolated; and (3) to analyze factors related to increased probability of having a positive blood culture. Methods: A retrospective, cross-sectional, 5-year descriptive study that includes all infants less than 3 months of age who presented with fever without source (FWS) and had a blood culture performed. Results: A blood culture was performed in 1018 (91.5%) of 1125 infants admitted, and a bacterial pathogen was grown in 23 (2.2%) of these; 8 were associated with a positive urine culture. The most frequently isolated pathogen was Escherichia coli (9), followed by Streptococcus pneumoniae (4). The risk factors detected by multivariate analysis were: (a) being classified as “not well-appearing” (12.5% vs. 1.8%; odds ratio: 8.37) and (b) leukocyturia and/or nitrituria in a urine dipstick test (5.6% vs. 1.6%; odds ratio: 3.73). C-reactive protein value was higher than white blood cell count and absolute neutrophil count in detecting bacteremia; a 70 g/L cut-off had a specificity of 93.8%, but sensitivity of only 69.6%. Conclusions: A positive blood culture rate of 2.2% was found in infants less than 3 months of age with FWS. C-reactive protein, white blood cell count, and absolute neutrophil count were not good bacteremia predictors. We recommend obtaining a blood culture in infants less than 3 months of age with FWS, particularly those patients considered “not well-appearing” and those with leukocyturia and/or nitrituria.

RAPID INFLUENZA TEST IN YOUNG FEBRILE INFANTS FOR THE IDENTIFICATION OF LOW-RISK PATIENTS

We included 381 febrile infants less than 3 months with a blood culture and a rapid influenza test done as part of study of fever. The prevalence of serious bacterial infections was significantly lower in patients in the positive rapid influenza test (RIT) group (3/113; 2.65%; 95% CI: 0–5.6) than in patients in the negative RIT group (47/268; 17.5%; 95% CI: 13–22.0). No patient with a positive RIT had a positive blood culture (vs. 8 in the negative RIT group, 2.98%, 95% CI: 0.9–5.0) The cerebrospinal fluid culture was positive in 5; all of them had a negative RIT. The use of RIT in the Emergency Department on previously well-appearing febrile young infants without a known source during influenza seasons can help to identify infants with a lower risk of developing serious bacterial infections. Routine blood culture may be no longer necessary in infants with a positive RIT.

Procalcitonin to detect invasive bacterial infection in non-toxic-appearing infants with fever without apparent source in the emergency department.

The reliability of procalcitonin as a predictor of invasive infection in infants <36 months of age with fever and nontoxic appearance was assessed in 868 patients, 15 (1.7%) of whom had invasive infection. The area under the receiver operating characteristic curve for procalcitonin was 0.87 (optimum cutoff 0.9 ng/mL, sensitivity 86.7%, specificity 90.5%), whereas for C-reactive protein it was 0.79 (optimum cutoff 91 mg/L, sensitivity 33.3%, specificity 95.9%). In infants with fever of <8 hours duration, the area under the receiver operating characteristic curve was 0.97 for procalcitonin and 0.76 for C-reactive protein. Procalcitonin was a useful biomarker to predict invasive infection in non–toxic-appearing infants with fever without apparent focus, particularly in febrile episodes of <8 hours duration.

Is 15 days an appropriate cut-off age for considering serious bacterial infection in the management of febrile infants?

Introduction: Febrile infants <3 months of age have a greater risk for serious bacterial infection (SBI). The risk is inversely correlated with age. Most protocols recommend admitting to hospital all febrile infants <28 days of age. However, as the prevalence of SBI is not homogenous in this age group, some authors have considered decreasing this cut-off age, allowing ambulatory management of selected patients meeting low-risk criteria. Objective: To determine whether 15 days is a suitable cut-off age for different approaches to the management of infants with fever. Patients and Methods: Cross-sectional descriptive study of infants <3 months of age with fever without a source seen between September 1, 2003 and August 30, 2010 in the pediatric emergency department of a tertiary teaching hospital. All infants <3 months of age with fever without a source (⩽38°C) were included. The following data were collected: age, sex, temperature, diagnosis, management in pediatric emergency department, and outcome. Results: Data were collected for 1575 infants; of whom, 311 (19.7%, 95% confidence intervals [CI]: 17.7–21.7) were found to have an SBI. The rate of SBI in the patients who were 15 to 21 days of age was 33.3% (95% CI: 23.7%–42.9%), similar to that among infants who were 7 to 14 days of age (31.9%, 95% CI: 21.1%–42.7%) and higher than among those older than 21 days of age (18.3%, 95% CI: 16.3–20.3%). Conclusions: Febrile infants 15 to 21 days of age had a rate of SBI similar to younger infants and higher than older age infants. It is not appropriate to establish the approach to management of infants with fever based on a cut-off age of 2 weeks.

Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection

Introduction Much effort has been put in the past years to create and assess accurate tools for the management of febrile infants. However, no optimal strategy has been so far identified. A sequential approach evaluating, first, the appearance of the infant, second, the age and result of the urinanalysis and, finally, the results of the blood biomarkers, including procalcitonin, may better identify low risk febrile infants suitable for outpatient management. Objective To assess the value of a sequential approach (‘step by step’) to febrile young infants in order to identify patients at a low risk for invasive bacterial infections (IBI) who are suitable for outpatient management and compare it with other previously described strategies such as the Rochester criteria and the Lab-score. Methods A retrospective comparison of three different approaches (step by step, Lab-score and Rochester criteria) was carried out in 1123 febrile infants less than 3 months of age attended in seven European paediatric emergency departments. IBI was defined as isolation of a bacterial pathogen from the blood or cerebrospinal fluid. Results Of the 1123 infants (IBI 48; 4.2%), 488 (43.4%) were classified as low-risk criteria according to the step by step approach (vs 693 (61.7%) with the Lab-score and 458 (40.7%) with the Rochester criteria). The prevalence of IBI in the low-risk criteria patients was 0.2% (95% CI 0% to 0.6%) using the step by step approach; 0.7% (95% CI 0.1% to 1.3%) using the Lab-score; and 1.1% (95% CI 0.1% to 2%) using the Rochester criteria. Using the step by step approach, one patient with IBI was not correctly classified (2.0%, 95% CI 0% to 6.12%) versus five using the Lab-score or Rochester criteria (10.4%, 95% CI 1.76% to 19.04%). Conclusions A sequential approach to young febrile infants based on clinical and laboratory parameters, including procalcitonin, identifies better patients more suitable for outpatient management.

Impact of the Pneumococcal Conjugate Vaccine in the Management of Highly Febrile Children Aged 6 to 24 Months in an Emergency Department

Objective: To evaluate the impact of the introduction of the heptavalent pneumococcal conjugate vaccine (PCV-7) in the management of children aged 6 to 24 months with high fever without source (FWS) in a pediatric emergency department (PED). Methods: Retrospective study of 770 patients aged 6 to 24 months attended in a pediatric ED between October 2004 and April 2005 with FWS 39°C or higher without alteration in the dipstick. Results: Out of 770 children, 215 (27.9%) were PCV-7 fully vaccinated (group A), and 555 (72.0%) were either incompletely PCV-7 vaccinated or not vaccinated at all (group B). Both groups did not show differences related to temperature registered at home or in the ED. Complete blood count (CBC) and blood culture were practiced in 163 (21.1%) patients, chest radiograph in 117 (15.1%), and lumbar puncture in 15 (1.9%). Thirty-three patients (4.3%) received a dose of intramuscular ceftriaxone, 20 (2.6%) were admitted to the observation unit, and 5 (0.6) were admitted to the hospital. One blood culture was positive, and 2 other children had a consolidation in the chest radiograph (all in group B). In patients not fully vaccinated with PCV-7, CBC and blood culture were practiced more frequently (group B, 26.6% vs. group A, 7%; P < 0.000001; odds ratio, 4.85 [limits, 2.70-8.83]) and ceftriaxone was also more frequently administered (group B, 5.3% vs. group A, 1.3%; P = 0.02; odds ratio, 4.04 [limits, 1.16-16.77]). Three children in group A (1.4%) were admitted to the observation unit or to floor versus 22 in group B (4%, P = 0.11). Conclusions: Inclusion of PCV-7 vaccinal status in the management of highly febrile children aged 6 to 24 months significantly reduces CBC and blood cultures practiced in the ED and the administration of ceftriaxone.

Well appearing young infants with fever without known source in the emergency department: are lumbar punctures always necessary?

We included 685 consecutive previously healthy well appearing infants younger than 3 months with fever without known source admitted to an Emergency Department without routinely performing lumbar punctures (LP). LP was performed in 198 infants. Of these, 36 (18.1%) showed pleocytosis. Two infants less than 15 days were diagnosed with bacterial meningitis and 47 with aseptic meningitis (6.8%). LP was not performed in 487 infants. Of these, 69 were admitted to ward (46 had urinary tract infection) and 418 were discharged. In this group, we registered 38 unscheduled revisits to the Emergency Department (four aseptic meningitis). All infants did well. It is unnecessary to perform a LP routinely on infants over 1 month of age. The decision to perform the LP in previously healthy and well appearing infants with fever without known source attended by an experienced paediatric emergency physician can be individualized with no subsequent adverse outcomes. This approach may lead to under-diagnosing nonbacterial meningitis.

Occult pneumonia in infants with high fever without source: a prospective multicenter study.

Background: The prevalence of pneumonia in infants with high fever without source (FWS; temperature, ≥39.0°C) and a white blood cell (WBC) count greater than 20 × 109/L (occult pneumonia) has been reported to be 20% before the introduction of the 7-valent pneumococcal conjugated vaccine (PCV7). This is the main reason for carrying out chest x-ray (CXR) on infants with high FWS. The aims of this study were to establish the prevalence of occult pneumonia in well-appearing infants with high FWS (temperature, ≥39.0°C) and a WBC count greater than 20 × 109/L in the era of PCV7 and to analyze the value of WBC, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as predictors of the risk of occult pneumonia in these patients. Patients and Methods: We conducted a multicenter prospective study in 4 pediatric emergency departments including children younger than 36 months with FWS (temperature, ≥39.0°C) and a WBC count higher than 20 × 109/L on whom a CXR was performed in the absence of respiratory findings. Physicians completed a questionnaire when observing the infant, and the attending physician or, when in doubt, the radiologist interpreted the CXR. Multivariable binary logistic regression was used to estimate the adjusted relative influences of the aforementioned factors on the prevalence of radiological pneumonia. Results: During an entire year (September 2006 to September 2007), we included 188 infants (aged 1-36 months; 56.2% were males) with high FWS and a WBC count greater than 20 × 109/L (range, 20-44.7 × 109/L) on whom a CXR was performed. Of the 188 chest radiographs obtained, 37 (19.7%) were interpreted by the radiologist. Consolidation in the chest radiographs was detected in 25 (13.3%). The probability of an infant with high FWS and WBC of 20 × 109/L or greater having pneumonia was related to 3 of the studied variables: age, ANC, and serum CRP level. The incidence of pneumonia increased with age (odds ratio [OR] of 2.62 for infants >12 months; 95% confidence interval [95% CI], 1.04-6.60), CRP level greater than 100 mg/L (OR, 3.18; 95% CI, 1.19-8.51), and ANC greater than 20 × 109/L (OR, 3.52; 95% CI, 1.37-9.06). White blood cell count was not predictive of occult pneumonia when ANC was taken into account. Conclusions: In the era of PCV7, the incidence of pneumonia in infants younger than 36 months with high FWS and WBC count greater than 20 × 109/L seems to be lower than that previously reported. However, this is not a uniform group because the incidence of pneumonia increases in infants older than 12 months and with higher ANC and serum CRP level.

Outpatient management of selected young febrile infants without antibiotics

Objective To analyse the outpatient management of selected febrile infants younger than 90 days without systematic lumbar puncture and antibiotics. Methods A prospective registry-based cohort study including all the infants ≤90 days with fever without a source (FWS) who were evaluated in a paediatric emergency department (ED) over a 7-year period (September 2007–August 2014). We analysed the outcome of those infants with low-risk criteria for serious bacterial infection (SBI) managed as outpatients without antibiotics and without undergoing a lumbar puncture. Low-risk criteria: Well appearing, older than 21 days of age, no leucocyturia, absolute neutrophil count ≤10 000, serum C reactive protein ≤20 mg/L, procalcitonin <0.5 ng/mL and no clinical deterioration during the stay in the ED (always <24 hours). Results 1472 infants with FWS attended the ED. Of these, 676 were classified to be at low risk for SBI without performing a lumbar puncture. After staying <24 hours in the short-stay unit of the ED, 586 (86.6%) were managed as outpatients without antibiotics. Two patients were diagnosed with SBI: one occult bacteraemia and one bacterial gastroenteritis. Both were afebrile when evaluated again and did well. No patient returned to the ED due to clinical deterioration. Fifty-one infants (8.7%) returned to the ED mainly due to persistence of fever or irritability. None was diagnosed with definite SBI or non-bacterial meningitis. Conclusions Outpatient management without antibiotics and systematic lumbar puncture is appropriate for selected febrile infants younger than 3 months of age with close follow-up.

Invasive bacterial infections in a paediatric emergency department in the era of the heptavalent pneumococcal conjugate vaccine.

Objective To describe the characteristics of patients diagnosed with invasive bacterial infections (IBIs) in a Paediatric Emergency Department (PED) following the introduction of the heptavalent pneumococcal conjugated vaccine (PCV7). Methods Descriptive retrospective study of children under 14 years of age diagnosed with IBIs in a PED of a tertiary hospital between January 2008 and December 2009. Results In this period we registered 123 396 episodes and 59 patients who were diagnosed with IBIs (22 patients under 1 year of age, 37.2%). Of these, 11 (18.6%) had some severe underlying condition and 38 (64.4%) were stable on arrival. The most common diagnoses were sepsis with/without meningitis (23, 38.9%) and bacteraemia (14, 23.7%), while the pathogens most frequently isolated were Streptococcus pneumoniae (23, 38.9%) and Neisseria meningitidis (18, 30.5%). Pathogens were isolated from blood in 57 patients and from the cerebrospinal fluid in eight (in these, the same bacterial species was isolated in the blood, except for two cases with S. pneumoniae). Of the pneumococci isolated, 80% corresponded to serotypes included in the 13-valent PCV13. In seven cases, pathogens were detected using only PCR analysis (N. meningitidis, four; S. pneumoniae, three). Twenty-five patients were admitted to the Paediatric Intensive Care Unit. No patient died but two had sequelae. Conclusion In the era of PCV7, pneumococcus is the leading cause of IBI in PED. The introduction of PCV13 may lead to a very significant decrease in the IBI rate and meningococcus may become the leading cause of IBI.