Background

Although community-acquired pneumonia (CAP) is one of the most common infections in children, no tools exist to risk stratify children with suspected CAP. We developed and validated a prediction model to risk stratify and inform hospitalization decisions in children with suspected CAP.

Methods

We performed a prospective cohort study of children aged 3 months to 18 years with suspected CAP in a pediatric emergency department. Primary outcome was disease severity, defined as mild (discharge home or hospitalization for <24 hours with no oxygen or intravenous [IV] fluids), moderate (hospitalization <24 hours with oxygen or IV fluids, or hospitalization >24 hours), or severe (intensive care unit stay for >24 hours, septic shock, vasoactive agents, positive-pressure ventilation, chest drainage, extracorporeal membrane oxygenation, or death). Ordinal logistic regression and bootstrapped backwards selection were used to derive and internally validate our model.

Results

Of 1128 children, 371 (32.9%) developed moderate disease and 48 (4.3%) severe disease. Severity models demonstrated excellent discrimination (optimism-corrected c-indices of 0.81) and outstanding calibration. Severity predictors in the final model included respiratory rate, systolic blood pressure, oxygenation, retractions, capillary refill, atelectasis or pneumonia on chest radiograph, and pleural effusion.

Conclusions

We derived and internally validated a score that accurately predicts disease severity in children with suspected CAP. Once externally validated, this score has potential to facilitate management decisions by providing individualized risk estimates that can be used in conjunction with clinical judgment to improve the care of children with suspected CAP.

Reports of the test accuracy of the urinalysis for diagnosing urinary tract infections (UTIs) in young febrile infants have been variable. We evaluated the test characteristics of the urinalysis for diagnosing UTIs, with and without associated bacteremia, in young febrile infants. We performed a planned secondary analysis of data from a prospective study of febrile infants ≤60 days old at 26 emergency departments in the Pediatric Emergency Care Applied Research Network. We evaluated the test characteristics of the urinalysis for diagnosing UTIs, with and without associated bacteremia, by using 2 definitions of UTI: growth of ≥50 000 or ≥10 000 colony-forming units (CFUs) per mL of a uropathogen. We defined a positive urinalysis by the presence of any leukocyte esterase, nitrite, or pyuria (>5 white blood cells per high-power field). Of 4147 infants analyzed, 289 (7.0%) had UTIs with colony counts ≥50 000 CFUs/mL, including 27 (9.3%) with bacteremia. For these UTIs, a positive urinalysis exhibited sensitivities of 0.94 (95% confidence interval [CI]: 0.91-0.97), regardless of bacteremia; 1.00 (95% CI: 0.87-1.00) with bacteremia; and 0.94 (95% CI: 0.90-0.96) without bacteremia. Specificity was 0.91 (95% CI: 0.90-0.91) in all groups. For UTIs with colony counts ≥10 000 CFUs/mL, the sensitivity of the urinalysis was 0.87 (95% CI: 0.83-0.90), and specificity was 0.91 (95% CI: 0.90-0.92). The urinalysis is highly sensitive and specific for diagnosing UTIs, especially with ≥50 000 CFUs/mL, in febrile infants ≤60 days old, and particularly for UTIs with associated bacteremia.

To assess the performance of the Yale Observation Scale (YOS) score and unstructured clinician suspicion to identify febrile infants ≤60 days of age with and without serious bacterial infections (SBIs). We performed a planned secondary analysis of a prospective cohort of non-critically ill, febrile, full-term infants ≤60 days of age presenting to 1 of 26 participating emergency departments in the Pediatric Emergency Care Applied Research Network. We defined SBIs as urinary tract infections, bacteremia, or bacterial meningitis, with the latter 2 considered invasive bacterial infections. Emergency department clinicians applied the YOS (range: 6-30; normal score: ≤10) and estimated the risk of SBI using unstructured clinician suspicion (<1%, 1%-5%, 6%-10%, 11%-50%, or >50%). Of the 4591 eligible infants, 444 (9.7%) had SBIs and 97 (2.1%) had invasive bacterial infections. Of the 4058 infants with YOS scores of ≤10, 388 (9.6%) had SBIs (sensitivity: 51/439 [11.6%]; 95% confidence interval [CI]: 8.8%-15.0%; negative predictive value: 3670/4058 [90.4%]; 95% CI: 89.5%-91.3%) and 72 (1.8%) had invasive bacterial infections (sensitivity 23/95 [24.2%], 95% CI: 16.0%-34.1%; negative predictive value: 3983/4055 [98.2%], 95% CI: 97.8%-98.6%). Of the infants with clinician suspicion of <1%, 106 had SBIs (6.4%) and 16 (1.0%) had invasive bacterial infections. In this large prospective cohort of febrile infants ≤60 days of age, neither the YOS score nor unstructured clinician suspicion reliably identified those with invasive bacterial infections. More accurate clinical and laboratory predictors are needed to risk stratify febrile infants.

Background

Febrile infants commonly present to emergency departments for evaluation.

Objective

We describe the variation in diagnostic testing and hospitalization of febrile infants ≤60 days of age presenting to the emergency departments in the Pediatric Emergency Care Applied Research Network.

Methods

We enrolled a convenience sample of non-critically ill-appearing febrile infants (temperatures ≥38.0°C/100.4°F) ≤60 days of age who were being evaluated with blood cultures in 26 Pediatric Emergency Care Applied Research Network emergency departments between 2008 and 2013. Patients were divided into younger (0-28 days of age) and older (29-60 days of age) cohorts for analysis. We evaluated diagnostic testing and hospitalization rates by infant age group using chi-square tests and by site using analysis of variance.

Results

Four thousand seven hundred seventy-eight patients were eligible for analysis, of whom 1517 (32%) were 0-28 days of age. Rates of lumbar puncture and hospitalization were high (>90%) among infants ≤28 days of age, with chest radiography (35.5%) and viral testing (66.2%) less commonly obtained. Among infants 29-60 days of age, lumbar puncture (69.5%) and hospitalization (64.4%) rates were lower and declined with increasing age, with chest radiography (36.5%) use unchanged and viral testing (52.7%) slightly decreased. There was substantial variation between sites in the older cohort of infants, with lumbar puncture and hospitalization rates ranging from 40% to 90%.

Conclusions

The evaluation and disposition of febrile infants ≤60 days of age is highly variable, particularly among infants who are 29-60 days of age. This variation demonstrates an opportunity to modify diagnostic and management strategies based on current epidemiology to safely decrease invasive testing and hospitalization.

Importance

Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach.

Objective

To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections.

Design, setting, and participants

Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type.

Exposure

RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections.

Main outcomes and measures

Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores.

Results

Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43).

Conclusions and relevance

In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

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.

Study objective

To describe the current epidemiology of bacteremia in febrile infants 60 days of age and younger in the Pediatric Emergency Care Applied Research Network (PECARN).

Methods

We conducted a planned secondary analysis of a prospective observational study of febrile infants 60 days of age and younger presenting to any of 26 PECARN emergency departments (2008 to 2013) who had blood cultures obtained. We excluded infants with significant comorbidities or critically ill appearance. The primary outcome was prevalence of bacteremia.

Results

Of 7,335 screened infants, 4,778 (65.1%) had blood cultures and were enrolled. Of these patients, 84 had bacteremia (1.8%; 95% confidence interval [CI] 1.4% to 2.2%). The prevalence of bacteremia in infants aged 28 days or younger (47/1,515) was 3.1% (95% CI 2.3% to 4.1%); in infants aged 29 to 60 days (37/3,246), 1.1% (95% CI 0.8% to 1.6%). Prevalence differed by week of age for infants 28 days of age and younger (0 to 7 days: 4/156, 2.6%; 8 to 14 days: 19/356, 5.3%; 15 to 21 days: 15/449, 3.3%; and 22 to 28 days: 9/554, 1.6%). The most common pathogens were Escherichia coli (39.3%; 95% CI 29.5% to 50.0%) and group B streptococcus (23.8%; 95% CI 16.0% to 33.9%). Bacterial meningitis occurred in 19 of 1,515 infants 28 days of age and younger (1.3%; 95% CI 0.8% to 2.0%) and 5 of 3,246 infants aged 29 to 60 days (0.2%; 95% CI 0.1% to 0.4%). Of 84 infants with bacteremia, 36 (42.9%; 95% CI 32.8% to 53.5%) had urinary tract infections (E coli 83%); 11 (13.1%; 95% CI 7.5% to 21.9%) had bacterial meningitis.

Conclusion

The prevalence of bacteremia and meningitis among febrile infants 28 days of age and younger is high and exceeds that observed in infants aged 29 to 60 days. E coli and group B streptococcus are the most common bacterial pathogens.