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.

UNLABELLED: It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

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.