Infections In Febrile Infants Research Articles

An all-inclusive model for predicting invasive bacterial infection in febrile infants age 7-60 days.

Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days. Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.4 F who underwent an ED evaluation with blood and urine cultures. Models to predict IBI were developed and validated respectively using a random 80/20 dataset split, including 10-fold cross-validation. We used precision recall curves as the classification metric. Of 4411 eligible infants with a mean age of 37 days, 29% had characteristics that would likely have excluded them from existing risk stratification protocols. There were 196 patients with IBI (4.4%), including 43 (1.0%) with bacterial meningitis. Analytic approaches varied in performance characteristics (precision recall range 0.04-0.29, area under the curve range 0.5-0.84), with the XGBoost model demonstrating the best performance (0.29, 0.84). The five most important variables were serum white blood count, maximum temperature, absolute neutrophil count, absolute band count, and age in days. A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms. Several models for the risk stratification of febrile infants have been developed. There is a need for a preferred comprehensive model free from limitations and algorithm exclusions that accurately predicts IBIs. This is the first study to derive an all-inclusive predictive model for febrile infants aged 7-60 days in a community ED sample with IBI as a primary outcome. This machine learning model demonstrates potential for clinical utility in predicting IBI.

Predictors of Invasive Bacterial Infection in Febrile Infants Aged 2 to 6 Months in the Emergency Department

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2 to 6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing.

Respiratory viral detection in the plasma and cerebrospinal fluid (CSF) of young febrile infants.

Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days. We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15-90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial infections (SBI). Twenty-four percent (30 of 126) of infants had plasma/CSF specimens positive for a respiratory virus. Enterovirus and parechovirus were the most commonly detected respiratory viruses. Viral positivity was highest in plasma samples at 25% (27 of 107) compared with CSF samples at 15% (nine of 62). SBIs (specifically urinary tract infections) were less common in infants with a sample positive for a respiratory virus compared to those without a virus detected (3% vs. 26%, p= 0.008). Our findings support the use of molecular diagnostics to include the identification of parechovirus in addition to enterovirus in febrile infants ≤90 days. Additionally, these data support the utilization of blood specimens to diagnose enterovirus and parechovirus infections in febrile infants ≤90 days.

Prevalence of invasive bacterial infection in febrile infants ≤90 days with a COVID-19 positive test: a systematic review and meta-analysis

BackgroundFebrile infants with an infection by influenza or enterovirus are at low risk of invasive bacterial infection (IBI).ObjectiveTo determine the prevalence of IBI among febrile infants ≤90 days old with...

Effect of Viral Illness on Procalcitonin as a Predictor of Bacterial Infection in Febrile Infants.

The impact of confirmed viral infections (CVI) on procalcitonin (PCT) levels in febrile infants aged 8-60 days with a bacterial illness (BI) is unknown. The objectives of the study were to (1) examine the association of CVI with PCT levels in patients with/without a concurrent BI, defined as bacteremia, meningitis, or urinary tract infection, and (2) assess PCT as a predictor of BI in infants with a concurrent CVI. In this single-center, retrospective cohort study, we examined febrile infants aged 8-60 days presenting between January 1, 2018 and December 31, 2020. PCT levels were compared between groups, according to results of bacterial cultures and viral tests, using the Wilcoxon rank test. The prediction ability of PCT to detect BI with/without concurrent CVI was assessed by using area under the curve from logistic regression. Patients included: 404 BI-/CVI+, 73 BI+/CVI-, 48 BI+/CVI+, and 138 BI-/CVI-. Median PCT level in the BI+/CVI+ group was significantly lower when compared to BI+/CVI- (0.36 ng/mL vs 0.89 ng/mL), but significantly higher than the BI-/CVI- group (0.36 ng/mL vs 0.1 ng/mL). The presence of a CVI reduced the sensitivity of PCT in BI detection (68% vs 44%), with minimal impact specificity (93% vs 96%). In previously healthy febrile infants 8-60 days old, the presence of a CVI reduces the sensitivity of PCT BI detection without impacting its specificity. The impact of a CVI on PCT levels in febrile infants has implications for how this marker of infection should be considered when assessing risk of BI in infants.

167 Risk of Serious Bacterial Infections in Febrile Infants Aged 7-90 Days With COVID-19

167 Risk of Serious Bacterial Infections in Febrile Infants Aged 7-90 Days With COVID-19

The Impact of Respiratory Symptoms on the Risk of Serious Bacterial Infection in Febrile Infants < 60 Days Old.

We aimed to evaluate the impact of respiratory symptoms and positive viral testing on the risk of serious bacterial infections (SBIs). A retrospective study was conducted that included infants (0-60 days) presenting with a fever between 2001 and 2022 at a tertiary hospital in northern Israel. Demographic, clinical, and laboratory parameters were collected, and risk factors for SBIs were analyzed. Data from a total of 3106 infants, including data from blood, urine, and CSF cultures, were obtained in 96.6%, 89%, and 29% of cases, respectively. A fever without respiratory symptoms (fever only) was present in 1312 infants, while 1794 had a fever and respiratory symptoms-427 were positive for a respiratory virus (virus+), 759 tested negative (virus-), and 608 were not tested. The SBI rate was 5.1% vs. 7.5% in the fever-and-respiratory group vs. the fever-only group (p = 0.004, OR = 0.65 (95% CI = 0.49-0.88)) and 2.8% vs. 7% in the virus+ vs. virus- group (p = 0.002, OR = 0.385, (95% CI = 0.203-0.728)). The male gender, an age < 1 month, leukocytosis > 15 × 109/L, or a CRP > 2 mg/dL increased the risk of SBIs. Respiratory symptoms or a confirmed viral infection reduced the risk of SBIs in the presence of the above risk factors. Respiratory symptoms and a positive viral test decreased the risk of SBIs. Combining rapid viral testing with clinical variables may identify low-risk infants. Despite the relatively low risk of SBIs in individuals with viral infections, conducting prospective studies remains essential for accurately predicting the occurrence of these potentially life-threatening infections.

Comparation on the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old

To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.

Methodological progress note: Machine learning methods in healthcare research.

Methodological progress note: Machine learning methods in healthcare research.

Derivation of a clinical-based model to detect invasive bacterial infections in febrile infants.

Febrile infants are at risk for invasive bacterial infections (IBIs) (i.e., bacteremia and bacterial meningitis), which, when undiagnosed, may have devastating consequences. Current IBI predictive models rely on serum biomarkers, which may not provide timely results and may be difficult to obtain in low-resource settings. The aim of this study was to derive a clinical-based IBI predictive model for febrile infants. This is a cross-sectional study of infants brought to two pediatric emergency departments from January 2011 to December 2018. Inclusion criteria were age 0-90 days, temperature ≥38°C, and documented gestational age, fever duration, and illness duration. To detect IBIs, we used regression and ensemble machine learning models and evidence-based predictors (i.e., sex, age, chronic medical condition, gestational age, appearance, maximum temperature, fever duration, illness duration, cough status, and urinary tract inflammation). We up-weighted infants with IBIs 8-fold and used 10-fold cross-validation to avoid overfitting. We calculated the area under the receiver operating characteristic curve (AUC), prioritizing a high sensitivity to identify the optimal cut-point to estimate sensitivity and specificity. Of 2311 febrile infants, 39 had an IBI (1.7%);the median age was 54 days (interquartile range: 35-71). The AUC was 0.819 (95% confidence interval: 0.762, 0.868). The predictive model achieved a sensitivity of 0.974 (0.800, 1.00) and a specificity of 0.530 (0.484, 0.575). Findings suggest that a clinical-based model can detect IBIs in febrile infants, performing similarly to serum biomarker-based models. This model may improve health equity by enabling clinicians to estimate IBI risk in any setting. Future studies should prospectively validate findings across multiple sites and investigate performance by age.

Diagnostic test accuracy of dipstick urinalysis for diagnosing urinary tract infection in febrile infants attending the emergency department

ObjectiveTo report the diagnostic test accuracy of dipstick urinalysis for the detection of urinary tract infections (UTIs) in febrile infants aged 90 days or less attending the emergency department (ED).DesignRetrospective...

Systematic review and meta-analysis assessing the diagnostic test accuracy of procalcitonin in the diagnosis of invasive bacterial infections in febrile infants: a study protocol

IntroductionYoung febrile infants are at higher risk of invasive bacterial infections (IBIs) compared with older children. The clinical features of IBI are subtle in this cohort mandating that clinicians take...

Value of Temperature for Predicting Invasive Bacterial Infection in Febrile Infants: A Spanish Pediatric Emergency Research Group (RISeuP-SPERG) Study.

This study aimed to analyze the prevalence of invasive bacterial infection (IBI) among infants younger than 90 days with fever without source according to the degree of fever. We performed a secondary analysis of a multicenter study with 19 participating Spanish pediatric emergency departments that included 3401 febrile infants 90 days or younger. Prevalence of IBI was 3.2% (5.3% among infants <29 days old, 2.5% among those 29-60 days old, and 2.2% among those 61-90 days old). Prevalence of bacteremia increased with the degree of fever, meanwhile the prevalence of bacterial meningitis did not. No cutoff point was useful for ruling out an IBI safely. Overall, 46.7% of the IBIs were diagnosed in patients with temperature <38.6° (sensitivity, 53.3%; negative likelihood ratio, 0.81). Performing blood tests should be recommended in infants 90 days or younger with temperature ≥38°C without source regardless of the degree of fever.

Variability in HSV Testing and Empiric Treatment in Febrile Infants

Source: Treasure JD, Shah SS, Hall M, et al for the Pediatric Research in Inpatient Settings Network and the Collaborative Antiviral Study Group. Variation in diagnostic testing and empiric acyclovir use for HSV infection in febrile infants. Hospital Pediatrics. 2021;11(9):922–930; doi.10.1542/hpeds.2020-003129Investigators from multiple institutions conducted a retrospective study to describe testing for herpes simplex virus (HSV) in febrile infants <60 days old, assess variation in testing and treatment across hospitals, and evaluate the effect of HSV testing on length of hospital stay (LOS) in these patients. For the study, data in the Pediatric Health Information System (PHIS) database were reviewed. PHIS includes administrative data such as demographics, diagnostic and procedure codes, and laboratory and pharmacy orders from encounters at pediatric hospitals. For the current study, data from 44 hospitals in 26 states and the District of Columbia were reviewed. Study participants were children ≤60 days old evaluated in the ED with an ICD-9 or ICD-10 code indicative of fever. Data abstracted on these children included use of HSV testing (culture or PCR), imaging and other diagnostic evaluations, hospital, demographics, orders for acyclovir, LOS, ICD-9 or ICD-10 codes for HSV infection, and severity of illness, as estimated in All Patient Refined-Diagnosis Related Groups (APR-DRG). The primary study outcome was rate of HSV testing, measured at the patient and hospital level. The hospital-level rates of acyclovir orders were also assessed. Secondary outcomes included rate of HSV infection in study patients. LOS was compared in study patients tested for HSV and those not tested using regression analyses and accounting for confounding variables such as age, hospital and APR-DRG estimated illness severity. Analyses were stratified by age (<22 days and 22–60 days).Data were analyzed on 24,534 ED encounters, including 6,027 (24.6%) patients <22 days old and 18,508 (75.4%) 22 to 60 days old. There were 108 children (0.44%) with a diagnostic code indicative of HSV infection, yielding rates of HSV disease of 1.08% for those <22 days old, and 0.23% for those 22 to 60 days of age. Rates of HSV testing were 39.4% and 12.0%, respectively, for children <22 and 22 to 60 days old. At the hospital level, the rate of HSV testing was 35.6% (interquartile range [IQR], 28% to 53%) for the younger age cohort, and 12% (IQR, 9% to 16%) for those 22 to 60 days old. There also was substantial variation in hospital-level rates of empiric acyclovir use (IQR, 68% to 90% for children <22 days old and 44% to 73% for those 22 to 60 days of age). The prevalence of additional testing also varied by age group and hospital. After adjusting for age, severity of illness and hospital, LOS was significantly longer in patients with HSV testing than in those not tested (mean LOS, 2.6 and 1.9 days, respectively; P <0.001).The authors conclude that substantial variation in diagnostic use of HSV testing in febrile infants ≤60 days old.Dr Winer has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The diagnosis and care of potential meningitis/encephalitis in young infants with fever has continually evolved over time (See AAP Grand Rounds. 2010;24[2]:17). As hospitals have moved away from HSV culture and toward HSV PCR testing and the delay in obtaining results has shortened, the safety and cost-effectiveness calculations leading to optimal strategy continue to change.1Although the current investigators were limited in their ability to evaluate duration of empiric acyclovir in children for whom HSV testing is negative, this likely has shortened over time. The LOS was longer for patients who had HSV testing performed, likely related to clinical concern by the physicians that led to the decision to test in the first place.HSV testing continues to evolve, with many hospitals starting to use multiplex PCR array panels which test for multiple viral (including HSV), bacterial, and even fungal pathogens.2 Some evidence exists that initial CSF results are not sensitive enough to preclude a meningitis/encephalitis panel,3 but concerns also exist about overdiagnosis and overtreatment with universal use of these panels.Significant variability exists in the testing and empiric acyclovir usage in febrile infants. Patients tested for HSV have longer LOS than those for whom no test is performed.Fever in young infants is relatively common; neonatal HSV infection, relatively rare. Unfortunately, the results of the current study underscore the need for guidance to allow informed HSV diagnostic and therapeutic decisions. (See AAP Grand Rounds. 2018;39(5):56.)4

Variation in Diagnostic Testing and Empiric Acyclovir Use for HSV Infection in Febrile Infants.

Clinicians evaluating for herpes simplex virus (HSV) in febrile infants must balance detection with overtesting, and there is no universally accepted approach to risk stratification. We aimed to describe variation in diagnostic evaluation and empirical acyclovir treatment of infants aged 0 to 60 days presenting with fever and determine the association between testing and length of stay (LOS). In this retrospective 44-hospital observational study, we used the Pediatric Health Information System database to identify infants aged ≤60 days evaluated for fever in emergency departments from January 2016 through December 2017. We described hospital-level variation in laboratory testing, including HSV, imaging and other diagnostic evaluations, acyclovir use, and LOS. We assessed the relationship between HSV testing and LOS using generalized linear mixed effects models adjusted for age and illness severity. In 24 535 encounters for fever, the median HSV testing frequency across hospitals was 35.6% (interquartile range [IQR]: 28.5%-53.5%) for infants aged 0 to 21 days and 12% (IQR: 8.6%-15.7%) for infants aged 22 to 60 days. Among HSV-tested patients, median acyclovir use across hospitals was 79.2% (IQR: 68.1%-89.7%) for those aged 0 to 21 days and 63.6% (IQR: 44.1%-73%) for those aged 22 to 60 days. The prevalence of additional testing varied substantially by hospital and age group. Risk-adjusted LOS for HSV-tested infants was significantly longer than risk-adjusted LOS for those not tested (2.6 vs 1.9 days, P < .001). Substantial variation exists in diagnostic evaluation and acyclovir use, and infants who received HSV testing had a longer LOS than infants who did not. This variability supports the need for further studies to help clinicians better risk-stratify febrile infants and to guide HSV testing and treatment decisions.

Epidemiology of serious bacterial infection in febrile infants under 3 months of age and diagnostic management in Mayotte

ObjectiveThis study aimed to determine the prevalence of serious bacterial infections (SBIs) in infants less than 90 days old presenting with fever on arrival at the emergency department (ED), and to assess the diagnostic management of febrile infants. DesignA retrospective study at Mamoudzou Hospital, Mayotte Island, French Department. SettingGeneral ED in the only pediatric hospital throughout the territory PatientsWe included infants less than 90 days old with a history of fever and bacterial investigation evaluated in the ED between 2016 and 2018. We excluded preterm infants (gestational age < 37 weeks) and those with known immunodeficiency or previous administration of antibiotics. ResultsA total of 594 infants were included. In all, 105 infants (17.7%) were diagnosed with an SBI and 28 (4.7%) with an invasive bacterial infection of which 1.34% was meningitis. The most frequent SBI was pneumonia (n = 69, 11.6%) followed by urinary tract infection (UTI; n = 37, 6.2%). Predominant pathogens (excluding contaminants) were Escherichia coli (51.2% of the UTI cases), group B Streptococcus (62.5% of meningitis cases), and Staphylococcus aureus (61.5% of bacteremia cases). Seven infants presented with bacterial pneumonia due to Staphylococcus aureus with Panton–Valentine leucocidin (PVL) exotoxin production. Ill-appearing infants, clinical signs of SBI and complex chronic condition were associated with a risk of SBI (respective odds ratio [OR]: 4.6, 95% confidence interval [CI]: 3–6.9; OR: 4.2, 95% CI: 2.8–6.4; and OR: 3.2, 95% CI: 1.2–8.5). The median age for SBI was 42 days (5–90). Fever without source (FWS) occurred more often in infants under 21 days of age (48.5% vs. 31.3% in older infants, p < 0.001). The median duration of fever at home was 24 h (6–96). Concerning management, in infants aged under 21 days, there were more lumbar punctures (58.3% vs. 23% in older infants, p < 0.001) and more frequent initiation of empiric antibiotics (62.6% vs. 42.7%, p < 0.001). Length of stay was also longer in this age range (5 days vs. 3 days, p = 0.037). ConclusionDelay in medical consultation in the case of fever, the risk of SBI regardless of age, and unusual epidemiology with many IBI due to Staphylococcus aureus with PVL exotoxin production are specific characteristics observed in our study. Knowledge of the current epidemiology of SBI in Mayotte would be useful for setting up a risk-stratified protocol in this population in the future.

Age- and sex-specific prevalence of serious bacterial infections in febrile infants ≤60 days, in Sweden.

The aim of the study was to describe age- and sex-specific prevalence of serious bacterial infections (SBI: urinary tract infection, bacteraemia, meningitis) among febrile infants ≤60days in Sweden. This is a retrospective study in 4 Pediatric Emergency Departments from 2014 to 2017, in previously healthy, full-term infants ≤60days with fever without a source. Of the 1,701 included infants, 214 (12.6%; 95% CI, 11.1-14.3) had an SBI. Urinary tract infection (UTI) was diagnosed in 196 (11.5%; 95% CI, 10.0-13.1) patients. In the ≤28 and 29-60days age-groups, meningitis prevalence was 0.9% (95% CI, 0.3-2.0) and 0.3% (95% CI, 0.1-0.8), whereas bacteraemia prevalence was 3.2% (95% CI, 1.9-4.9) and 0.6% (95% CI, 0.2-1.3). The SBI prevalence was higher in boys 16.0% (95% CI, 13.8-18.5) than girls 8.0% (95% CI, 6.2-10.2; p<0.001), due to 2-fold higher UTI risk. The prevalence of meningitis in boys was 0.3% (95% CI, 0.1- 0.9) vs. 0.7% (95% CI, 0.2-1.6) in girls and of bacteraemia 1.8% (95% CI, 1.0-2.8) vs. 1.0% (95% CI, 0.4-2.0), respectively. The total SBI prevalence was 12.6%, and UTI represented the vast majority. The prevalence of bacteraemia and meningitis was low, particularly in the 29-60days age group, without significant difference between boys and girls.

Early prediction of serious infections in febrile infants incorporating heart rate variability in an emergency department: a pilot study

BackgroundEarly differentiation of febrile young infants with from those without serious infections (SIs) remains a diagnostic challenge. We sought to (1) compare vital signs and heart rate variability (HRV) parameters...

Prevalence of Bandemia in Respiratory Viral Infections: A Pediatric Emergency Room Experience.

Objective: The aim of this study was to examine the prevalence of bandemia in confirmed respiratory viral infections in febrile infants and children presenting to the emergency department.Methods: An observational retrospective study from January 1, 2016, through December 31, 2016, was conducted in patients between the ages of ≥ 1 month and ≤ 5 years presenting to the emergency room with fever and who had a complete blood cell count performed. Patients were separated into seven groups based on the type of respiratory viral infection. Inclusion criteria strictly counted children with viral infections and absence of clinical and laboratory evidence of a bacterial coinfection.Results: A total of 419 patients had a documented viral infection. A significant proportion of these children were found to have bandemia; children with adenovirus (17%), respiratory syncytial virus (RSV) (14.9%), human metapneumovirus (hMPV) (13%), and parainfluenza virus (7.9%) had the highest prevalence when the cutoff for bandemia was set at 10%. The prevalence increased to 35.3, 30.9, 40.3, and 15.8% for adenovirus, RSV, hMPV, and parainfluenza virus, respectively, when this cutoff was lowered further to 5%.Conclusion: Band neutrophils are detected frequently in confirmed respiratory viral infections particularly during early stages.

Association of Cough Status With Bacterial Infections in Febrile Infants.

To examine the association between cough status and bacterial infections (BIs) to more accurately stratify risk and predict BIs in febrile infants. A retrospective cohort study was performed by identifying all infants ≤60 days old with temperature ≥38°C at an urban pediatric emergency department from 2014 to 2016. The Rochester Risk model was used to stratify risk. Cough status (with or without) was the main covariate of interest. The primary outcome was a BI, including urinary tract infection, bacteremia, or meningitis. Analyses consisted of descriptive statistics, simple and multiple regression to compare the odds of BI on the basis of cough status, as well as χ2 statistics to compare the BI rates among high-risk infants with and without cough. Of 508 febrile infants ≤60 days old, 46 (9.1%) had a BI, 13 of which were either bacteremia or meningitis. There were no BIs among low-risk infants with a cough. The odds of BI increased progressively, peaking at 14.6 (95% confidence interval: 4.3-49.7) for high-risk infants without a cough. The adjusted odds of BI among infants with cough was 0.47 (95% confidence interval: 0.22-0.99). In our findings, an inverse relationship is demonstrated between presence of cough and odds of BI, suggesting that cough status may be a useful marker of viral infections in febrile infants. Considering that detecting cough status is noninvasive, inexpensive, and immediately available, it represents an attractive value-based risk factor to enhance current BI prediction models.