Well-appearing Infants Research Articles

Implementing a Model to Predict Risk of Neonatal Sepsis in late-preterm and term infants: A Quality Improvement Initiative

BACKGROUND: In the United States, as many as 10% of well-appearing infants born at ≥34 weeks are evaluated and treated with antibiotics for risk of infection. The actual incidence of early onset sepsis (EOS) is estimated at 0.5/1000 live births (1). In a large multi-center medical system, the development and retrospective application of an electronic medical record (EMR) based clinical prediction tool, which was based on maternal and infant characteristics, predicted a 2/3 reduction in infant sepsis evaluation and antibiotic exposure (2,3). Our aim is the prospective implementation of this …

Clinical Monitoring of Well-Appearing Infants Born to Mothers With Chorioamnionitis.

The risk of early-onset sepsis is low in well-appearing late-preterm and term infants even in the setting of chorioamnionitis. The empirical antibiotic strategies for chorioamnionitis-exposed infants that are recommended by national guidelines result in antibiotic exposure for numerous well-appearing, uninfected infants. We aimed to reduce unnecessary antibiotic use in chorioamnionitis-exposed infants through the implementation of a treatment approach that focused on clinical presentation to determine the need for antibiotics. Within a quality-improvement framework, a new treatment approach was implemented in March 2015. Well-appearing late-preterm and term infants who were exposed to chorioamnionitis were clinically monitored for at least 24 hours in a level II nursery; those who remained well appearing received no laboratory testing or antibiotics and were transferred to the level I nursery or discharged from the hospital. Newborns who became symptomatic were further evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing, culture results, and clinical outcomes were collected. Among 277 well-appearing, chorioamnionitis-exposed infants, 32 (11.6%) received antibiotics during the first 15 months of the quality-improvement initiative. No cases of culture result-positive early-onset sepsis occurred. No infant required intubation or inotropic support. Only 48 of 277 (17%) patients had sepsis laboratory testing. The implementation of the new approach was associated with a 55% reduction (95% confidence interval 40%-65%) in antibiotic exposure across all infants ≥34 weeks' gestation born at our hospital. A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes.

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.

Anti-microbial stewardship: antibiotic use in well-appearing term neonates born to mothers with chorioamnionitis.

To determine if implementation of a protocol based on a neonatal early-onset sepsis (EOS) calculator developed by Kaiser Permanente would safely reduce antibiotic use in well-appearing term infants born to mothers with chorioamnionitis in the unique setting of an Observation Nursery. Data obtained from a retrospective chart review of well-appearing term infants born between 2009 and 2016 were entered into the EOS calculator to obtain management recommendations. Three hundred and sixty-two infants met the study criteria. Management according to the EOS calculator would reduce antibiotic use from 99% to 2.5% (P<0.0001) of patients. Average length of therapy would also decrease from 2.08 to 0.05 days (P<0.0001). One infant, who remained asymptomatic, had Enterococcus bacteremia and received a 7-day course of broad-spectrum antibiotics. Culture-positive sepsis in asymptomatic neonates born to mothers with chorioamnionitis is rare. Management according to the EOS calculator would markedly reduce the potential complications of antibiotic use. These data should initiate re-examination of existing protocols for management of this cohort of patients.

Derivation and Validation of a Serum Biomarker Panel to Identify Infants With Acute Intracranial Hemorrhage

Abusive head trauma is the leading cause of death from physical abuse. Missing the diagnosis of abusive head trauma, particularly in its mild form, is common and contributes to increased morbidity and mortality. Serum biomarkers may have potential as quantitative point-of-care screening tools to alert physicians to the possibility of intracranial hemorrhage. To identify and validate a set of biomarkers that could be the basis of a multivariable model to identify intracranial hemorrhage in well-appearing infants using the Ziplex System. Binary logistic regression was used to develop a multivariable model incorporating 3 serum biomarkers (matrix metallopeptidase-9, neuron-specific enolase, and vascular cellular adhesion molecule-1) and 1 clinical variable (total hemoglobin). The model was then prospectively validated. Multiplex biomarker measurements were performed using Flow-Thru microarray technology on the Ziplex System, which has potential as a point-of-care system. The model was tested at 3 pediatric emergency departments in level I pediatric trauma centers (Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Primary Children's Hospital, Salt Lake City, Utah; and Lurie Children's Hospital, Chicago, Illinois) among well-appearing infants who presented for care owing to symptoms that placed them at increased risk of abusive head trauma. The study took place from November 2006 to April 2014 at Children's Hospital of Pittsburgh, June 2010 to August 2013 at Primary Children's Hospital, and January 2011 to August 2013 at Lurie Children's Hospital. A mathematical model that can predict acute intracranial hemorrhage in infants at increased risk of abusive head trauma. The multivariable model, Biomarkers for Infant Brain Injury Score, was applied prospectively to 599 patients. The mean (SD) age was 4.7 (3.1) months. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive (95% CI, 87.7-90.4) and 48.0% specific (95% CI, 47.3-48.9) for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage. The Biomarkers for Infant Brain Injury Score, a multivariable model using 3 serum biomarker concentrations and serum hemoglobin, can identify infants with acute intracranial hemorrhage. Accurate and timely identification of intracranial hemorrhage in infants without a history of trauma in whom trauma may not be part of the differential diagnosis has the potential to decrease morbidity and mortality from abusive head trauma.

Variation in Sepsis Evaluation Across a National Network of Nurseries.

The extent to which clinicians use currently available guidelines for early-onset sepsis (EOS) screening has not been described. The Better Outcomes through Research for Newborns network represents 97 nurseries in 34 states across the United States. The objective of this study was to describe EOS risk management strategies across a national sample of newborn nurseries. A Web-based survey was sent to each Better Outcomes through Research for Newborns network nursery site representative. Nineteen questions addressed specific practices for assessing and managing well-appearing term newborns identified at risk for EOS. Responses were received from 81 (83%) of 97 nurseries located in 33 states. Obstetric diagnosis of chorioamnionitis was the most common factor used to identify risk for EOS (79 of 81). Among well-appearing term infants with concern for maternal chorioamnionitis, 51 of 79 sites used American Academy of Pediatrics or Centers for Disease Control and Prevention guidelines to inform clinical care; 11 used a published sepsis risk calculator; and 2 used clinical observation alone. Complete blood cell count (94.8%) and C-reactive protein (36.4%) were the most common laboratory tests obtained and influenced duration of empirical antibiotics at 13% of the sites. Some degree of mother-infant separation was required for EOS evaluation at 95% of centers, and separation for the entire duration of antibiotic therapy was required in 40% of the sites. Substantial variation exists in newborn EOS risk assessment, affecting the definition of risk, the level of medical intervention, and ultimately mother-infant separation. Identification of the optimal approach to EOS risk assessment and standardized implementation of such an approach could affect care of a large proportion of newborns.

Evaluation of the bedside Quikread go® CRP test in the management of febrile infants at the emergency department.

Recently C-reactive protein (CRP) point-of-care tests have been developed. We aimed to validate a bedside CRP test (QuikRead go® CRP), to compare it with the laboratory CRP (ARCHITECT c8000 Abbott, Germany) test in children with fever without source (FWS), and to evaluate the optimal CRP cut-off value to identify those patients at a high risk for serious bacterial infection (SBI). The CRP bedside test was prospectively performed in capillary blood samples concurrently with the laboratory CRP testing for 283 well-appearing infants aged 1 to 24months with FWS attending the emergency department (ED) between May 2013 and August 2015. The mean difference between the laboratory CRP and the QuikRead go CRP values was 0.71mg/L (p = 0.444). Pearson's correlation coefficient between the CRPs was r = 0.929 (p < 0.001). SBI was diagnosed in 34 patients (12.0%). The area under the receiver operating characteristics (ROC) curve obtained was 0.87 (95%CI: 0.82-0.90) for an optimal CRP cut-off value of > 10mg/L (sensitivity: 94.1%, specificity: 49.0%, positive predictive value: 20.1%, negative predictive value: 98.4%), as a predictor of SBI. Nearly 45% of the patients were at a low risk for SBI according to CRP value; thus, additional laboratory tests would have been hypothetically avoided. There was a very strong, positive correlation between the QuikRead go CRP test and laboratory CRP determination. The QuikRead go CRP test provides reliable results to rule out SBI. Its implementation at the ED would improve the management of infants with FWS.

Human Rhinovirus Detection by PCR in Febrile Infants and Risk of Concomitant Bacterial Infection

BackgroundStudies have shown that well-appearing febrile infants (FI) with viral respiratory infections have a reduced risk of bacterial infections (BI; urinary tract infection, bloodstream infection, meningitis). Respiratory testing by PCR allows detection of human rhinovirus (HRV), but few data exist on the risk of concomitant BI in HRV-positive FI.MethodsWe identified well-appearing FI 1–90 days old within Intermountain Healthcare evaluated in the ED or inpatient setting (IP) with viral respiratory testing by PCR (RVPCR) from August 2007 to August 2016. Respiratory viruses detected by RVPCR included: adenovirus, coronavirus, human metapneumovirus, influenza A/B, parainfluenza 1–4, RSV and HRV. We used relative risk (RR) to compare the risk of BI for infants with HRV vs. non-HRV viruses detected. Similarly, we used RR to compare risk of UTI and invasive bacterial infection (IBI; bacteremia and meningitis) for infants with HRV detected compared with those who were virus negative.Results10,964 FI were evaluated in the ED/IP during the study period. 4037 (37%) had RVPCR and were included. 2212 (55%) FI were positive for a respiratory virus and 73% were 29–90 days old. HRV was detected alone in 1392 (34%) and non-HRV viruses were detected in 820 (20%). The overall frequency of BI in the cohort was 9.5%. FI with HRV were more likely to have BI when compared with those with non-HRV viruses [7.8% vs 3.7% P < 0.0001; RR 2.12 (95% CI; 1.43–3.15)].When compared with virus-negative infants, HRV detection in infants 1–28 days did not decrease the risk for UTI [RR 0.87 (95% CI 0.58–1.29)]; risk of IBI was statistically decreased [RR 0.41 (95% CI 0.19–0.88)] but with wide CI approaching 1 suggesting that this may not be clinically meaningful. Similarly, UTI risk in infants 29–90 days was statistically lower with HRV detection [RR 0.78 (95% CI 0.65–0.95)], but unlikely to be clinically important. For infants 29–90 days with HRV, risk of IBI was statistically decreased [RR 0.52 (95% CI 0.34–0.80)] with possible clinical relevance.ConclusionHRV detection was common in young febrile infants. Infants with HRV were at higher risk of BI than infants with non-HRV infection. Detection of HRV did not meaningfully change risk for UTI at any age or meaningfully impact risk of IBI in infants 1–28 days. HRV detection may be associated with a decreased risk for IBI in infants 29–90 days.Disclosures A. J. Blaschke, BioFire Diagnostics LLC: Collaborator, Have intellectual property in BioFire Diagnostics through the University of Utah and Investigator, Licensing agreement or royalty and Research support; J. Daly, Biofire: Grant Investigator, Grant recipient; C. L. Byington, BioFire: Collaborator and Grant Investigator, Licensing agreement or royalty and Research grant

Early-Onset Neonatal Sepsis: A Continuing Problem in Need of Novel Prevention Strategies.

* Abbreviations: ABC — : Active Bacterial Core surveillance EOS — : early-onset neonatal sepsis GBS — : group B streptococcus IAP — : intrapartum antimicrobial prophylaxis Early-onset neonatal sepsis (EOS) remains a feared cause of severe illness and death among infants of all birthweights and gestational ages, with particular impact among preterm infants. Centers for Disease Control and Prevention investigators have studied the changing epidemiology of invasive EOS for several decades. The Active Bacterial Core surveillance (ABCs) network, a collaboration between the Centers for Disease Control and Prevention, state health departments, and universities, was established in 1995 to address emerging infectious diseases of public health importance, including infections due to major neonatal pathogens.1,2 ABCs data are remarkable because of the geographic distribution and size of the population-based network, laboratory-based identification of cases, linked epidemiologic and laboratory data, and surveillance over many years. In this issue of Pediatrics , Schrag and colleagues3 present ABCs data on the epidemiology of early-onset neonatal sepsis collected over a recent 10-year period, with special attention to group B streptococcal (GBS) and Escherichia coli infections. Invasive GBS infection among neonates, identified in the 1960s,4 emerged as the most common cause of EOS, with high risk of morbidity and mortality. National guidelines … Address correspondence to Barbara J. Stoll, MD, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St, MSB G.150, Houston, TX 77030. E-mail: barbara.j.stoll{at}uth.tmc.edu

Urinary Imaging Findings in Young Infants With Bacteremic Urinary Tract Infection.

To describe renal ultrasound (RUS) and voiding cystourethrogram (VCUG) findings and determine predictors of abnormal imaging in young infants with bacteremic urinary tract infection (UTI). We used retrospective data from a multicenter sample of infants younger than 3 months with bacteremic UTI, defined as the same pathogenic organism in blood and urine. Infants were excluded if they had any major comorbidities, known urologic abnormalities at time of presentation, required intensive unit care, or had no imaging performed. Imaging results as stated in the radiology reports were categorized by a pediatric urologist. Of the 276 infants, 19 were excluded. Of the remaining 257 infants, 254 underwent a RUS and 224 underwent a VCUG. Fifty-five percent had ≥1 RUS abnormalities. Thirty-four percent had ≥1 VCUG abnormalities, including vesicoureteral reflux (VUR, 27%), duplication (1.3%), and infravesicular abnormality (0.9%). Age <1 month, male sex, and non-Escherichia coli organism predicted an abnormal RUS, but only non-E coli organism predicted an abnormal VCUG. Seventeen of 96 infants (17.7%) with a normal RUS had an abnormal VCUG: 15 with VUR (Grade I-III = 13, Grade IV = 2), 2 with elevated postvoid residual, and 1 with infravesical abnormality. Although RUS and VCUG abnormalities were common in this cohort, the frequency and severity were similar to previous studies of infants with UTIs in general. Our findings do not support special consideration of bacteremia in imaging decisions for otherwise well-appearing young infants with UTI.

Validation of the Pittsburgh Infant Brain Injury Score for Abusive Head Trauma.

Abusive head trauma is the leading cause of death from physical abuse. Misdiagnosis of abusive head trauma as well as other types of brain abnormalities in infants is common and contributes to increased morbidity and mortality. We previously derived the Pittsburgh Infant Brain Injury Score (PIBIS), a clinical prediction rule to assist physicians deciding which high-risk infants should undergo computed tomography of the head. Well-appearing infants 30 to 364 days of age with temperature <38.3°C, no history of trauma, and a symptom associated with an increased risk of having a brain abnormality were eligible for enrollment in this prospective, multicenter clinical prediction rule validation. By using a predefined neuroimaging paradigm, subjects were classified as cases or controls. The sensitivity, specificity, and negative and positive predictive values of the rule for prediction of brain injury were calculated. A total of 1040 infants were enrolled: 214 cases and 826 controls. The 5-point PIBIS included abnormality on dermatologic examination (2 points), age ≥3.0 months (1 point), head circumference >85th percentile (1 point), and serum hemoglobin <11.2g/dL (1 point). At a score of 2, the sensitivity and specificity for abnormal neuroimaging was 93.3% (95% confidence interval 89.0%-96.3%) and 53% (95% confidence interval 49.3%-57.1%), respectively. Our data suggest that the PIBIS accurately identifies infants who would benefit from neuroimaging to evaluate for brain injury. An implementation analysis is needed before the PIBIS can be integrated into clinical practice.

Chorioamnionitis and early-onset neonatal infection.

Chorioamnionitis is associated with early-onset neonatal infection, but only a small fraction of women with chorioamnionitis has an infected infant. US guidelines recommend empiric antibiotics for well-appearing infants of mothers with chorioamnionitis. A 4-year US study of early-onset neonatal infection (defined as positive blood or CSF culture ≤72 h) collected data about clinical or histopathological maternal chorioamnionitis. An analysis aimed to determine how many chorioamnionitis-exposed infected infants were asymptomatic at birth.1 The incidence of early-onset infection was 1.02 per 1000 live births (389 episodes in 396 586 births). The mothers of 60% of infected infants had a diagnosis of chorioamnionitis; 29 (13%) of 229 had no reported symptoms at 6 h, and 21 (9%) remained symptom free at 72 h. Asymptomatic infants were no more likely than symptomatic infants to have received intrapartum antibiotics. Most infected infants (65%) were born preterm, 91% of them at 22–33 weeks' gestation, itself a risk factor for infection likely to warrant starting antibiotics. The authors estimated that, if current guidelines were followed and depending on chorioamnionitis prevalence, 60 to 1400 newborns would receive antibiotics for each infected asymptomatic newborn. Some chorioamnionitis-exposed newborns with culture-confirmed early-onset neonatal infection are asymptomatic, but empiric treatment on the basis of chorioamnionitis also results in treating large numbers of asymptomatic infants.

National Survey on the Impact of Viral Testing for the ED and Inpatient Management of Febrile Young Infants.

Well-appearing febrile infants with viral illnesses cannot be distinguished from those with occult life-threatening infections. Infants with respiratory viruses are less likely to have serious bacterial infections; however, current risk-stratification criteria predate widespread viral testing and there are limited data to safely inform physician management with this now common diagnostic tool. This study sought to explore the possible impact of respiratory virus testing on clinical decision-making for the management of febrile young infants<6 weeks old. A scenario-based survey was sent to emergency department (ED) and inpatient physicians at all 16 Canadian tertiary pediatric centers. Participants were asked questions regarding management decisions with and without results of respiratory virus testing. Response rate was 78% (n=330; 190 ED, 140 inpatient). Detection of a respiratory virus reduced admission rates among 3-week-old (83% vs 95%, P<.001) and 5-week-old infants (36% vs 52%, P<.001). Similarly, empirical antibiotic treatment was decreased by detection of a respiratory virus for 3-week-old (65% vs 92%, P<.001) and 5-week-old infants (25% vs 39%, P<.001). Management of 5-week-old infants differed between ED and inpatient physicians, both in the presence and absence of a respiratory virus. There was no consensus among inpatient physicians regarding admission duration for well infants with a detectable respiratory virus and otherwise negative workup. Respiratory virus testing appears to influence clinical decision-making for febrile infants<6 weeks, reducing both rates of admission and antimicrobial treatment. Important work is needed to better understand how to safely incorporate viral testing for the management of this vulnerable patient population.

A Prospective Multicenter Study of Leukopenia in Infants Younger Than Ninety Days With Fever Without Source.

Little is known about the value of leukopenia for assessing the risk of having a bacterial infection in young febrile infants. Infants younger than 90 days with fever without source were prospectively recruited between October 2011 and September 2013 in 19 Spanish Pediatric Emergency Departments. We analyzed the prevalence of invasive bacterial infection (IBI, positive blood or cerebrospinal fluid culture) and non-IBI (urinary tract infections and any other microbiologically confirmed bacterial infection excluding IBIs) by leukocyte count and general appearance. Among the 3401 infants recruited, 680 were diagnosed with non-IBIs (19.9%) and 107 with IBIs (3.1%). Overall, 244 infants had leukopenia (<5000 cells/mcL), 2369 a normal leukocyte count and 790 leukocytosis (>15,000 cells/mcL). Among the 3034 well-appearing patients, those with leukopenia had a lower prevalence of non-IBI [8.1% vs. 14.7%; odds ratio (OR) 0.51 (95% confidence interval (CI): 0.29-0.88)] and a similar prevalence of IBI [2.5% vs. 2.0%; OR, 1.20 (95% CI: 0.44-3.44)] compared with those with a normal leukocyte count. Among the 367 not-well-appearing infants, those with leukopenia had a similar prevalence of non-IBI [8.9% vs. 14.7%; OR, 0.57 (95% CI: 0.16-1.79)] and a higher prevalence of IBI [17.8% vs. 6.9%; OR, 2.90 (95% CI: 1.06-7.78)]. In the subgroup of well-appearing infants 22-90 days old without leukocyturia according to urine dipstick results, prevalence of both non-IBIs and IBIs was similar in patients with leukopenia and those with a normal leukocyte count. Leukopenia in well-appearing young febrile infants should not be considered a risk factor for having a bacterial infection.

Development of a screening MRI for infants at risk for abusive head trauma.

Abusive head trauma (AHT) is an important cause of morbidity in infants. Identifying which well-appearing infants are at risk for AHT and need neuroimaging is challenging, and concern about radiation exposure limits the use of head CT. Availability of an MRI protocol that is highly sensitive for intracranial hemorrhage would allow for AHT screening of well-appearing infants without exposing them to radiation. To develop a screening MRI protocol to identify intracranial hemorrhage in well-appearing infants at risk for AHT. Infants enrolled in a parent study of well-appearing infants at increased risk for AHT were eligible for the current study if they underwent both head CT and conventional brain MRI. A derivation cohort of nine infants with AHT was used to identify sequences that provided the highest sensitivity for intracranial hemorrhage. A validation cohort of 78 infants including both controls with normal neuroimaging and cases with AHT was used to evaluate the accuracy of the selected sequences. Three pulse sequences - axial T2, axial gradient recalled echo (GRE) and coronal T1-W inversion recovery - were 100% sensitive for intracranial hemorrhage in the derivation cohort. The same sequences were 100% sensitive (25/25) and 83% specific (44/53) for intracranial hemorrhage in the validation cohort. A screening MRI protocol including axial T2, axial GRE and coronal T1-W inversion recovery sequences is highly sensitive for intracranial hemorrhage and may be useful as a screening tool to differentiate well-appearing infants at risk for AHT who should undergo head CT from those who can safely be discharged without head CT. Additional research is needed to evaluate the feasibility of this approach in clinical practice.

Lab-score is a valuable predictor of serious bacterial infection in infants admitted to hospital.

Parents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7% and specificity of 98.6% in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75% and specificity of 97.7%. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.

Epidemiology of Bacteremia in Previously Healthy Febrile Infants: A Follow-up Study

Describe the etiology of bacteremia among a geographically diverse sample of previously well infants with fever admitted for general pediatric care and to characterize demographic and clinical characteristics of infants with bacteremia according to bacterial etiology. We hypothesized that the epidemiology of bacteremia in febrile infants from a geographically diverse cohort would show similar results to smaller or single-center cohorts previously reported. This was a retrospective review of positive, pathogenic blood cultures in previously healthy, febrile infants≤90 days old admitted to a general unit. In total, there were 17 participating sites from diverse geographic regions of the United States. Cultures were included if the results were positive for bacteria, obtained from an infant 90 days old or younger with a temperature≥38.0°C, analyzed using an automated detection system, and treated as pathogenic. Escherichia coli was the most prevalent species, followed by group B Streptococcus, Streptococcus viridans, and Staphylococcus aureus. Among the most prevalent bacteria, there was no association between gender and species (Ps>.05). Age at presentation was associated only with Streptococcus pneumoniae. There were no cases of Listeria monocytogenes. Our study confirms the data from smaller or single-center studies and suggests that the management of febrile well-appearing infants should change to reflect the current epidemiology of bacteremia. Further research is needed into the role of lumbar puncture, as well as the role of Listeria and Enterococcus species in infantile bacteremia.

Prevalence and predictors of bacterial meningitis in young infants with fever without a source.

Classical criteria differ when performing cerebrospinal fluid (CSF) analysis in infants younger than 90 days with fever without a source (FWS). Our objectives were to analyze the prevalence and microbiology of bacterial meningitis in this group and its prevalence in relation to clinical and laboratory risk factors. This is a substudy of a prospective registry including all infants of this age with FWS seen between September 2003 and August 2013 in a Pediatric Emergency Department of a Tertiary Teaching Hospital. Lumbar puncture was performed in 639 (27.0%) of the 2362 infants with FWS seen, the rate being higher in not well-appearing infants [60.9% vs. 25.7%; odds ratio (OR), 4.49] and in those ≤21 days old (70.1% vs. 20.4%; OR, 9.14). Eleven infants were diagnosed with bacterial meningitis: 9 were ≤21 days old (prevalence 2.8% vs. 0.1%; OR, 30.42) and 5 were not well-appearing infants (5.7% vs. 0.2%; OR, 23.06). Bacteria isolated were Streptococcus agalactiae (3), Escherichia coli (3), Listeria monocytogenes (3), Streptococcus pneumoniae (1) and Neisseria meningitidis (1). None of the 1975 well-appearing infants >21 days old were diagnosed with bacterial meningitis, regardless of whether biomarkers were altered. In infants younger than 90 days with FWS, performing CSF analysis for ruling out bacterial meningitis must be strongly considered in not well-appearing infants and in those ≤21 days old. The recommendation of systematically performing CSF analysis in well-appearing infants 22-90 days of age on the basis of analytical criteria alone must be reevaluated.

Earlier Discharge of Febrile Infants

Source: Biondi EA, Mischler M, Jerardi KE, et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014; 168(9): 844– 849; doi: 10.1001/jamapediatrics.2014.895Investigators at multiple medical centers affiliated with the Pediatric Research in Inpatient Settings (PRIS) network conducted a retrospective, cross-sectional evaluation of time to positivity (TTP) of blood culture results in febrile infants <91 days of age. Microbiology laboratories at each study site supplied all positive culture results obtained in a non-ICU setting; individual site investigators reviewed records for eligibility. All sites used a BACTEC automated blood culture detection system and collected at least 2 consecutive years of data ending January 1, 2013. Blood cultures were included if positive for bacteria in an infant <91 days of age with a temperature ≥38.0°C who was treated with a full course of antibiotics. With this definition, cultures that were positive for bacteria typically classified as contaminants were included if the treating clinicians treated the patient with a full course of antibiotics. Cultures from infants in an ICU, surgical patients, or patients with central lines were excluded. Clinical information, TTP in minutes (the time the machine alarmed minus the time the culture was placed in the analyzer), and bacterial species were collected. Each patient was stratified as low risk or nonlow risk based on the Rochester criteria.1 The primary aim of the study was to determine the proportion of positive cultures that become positive >24 hours after collection.A total of 392 blood cultures that were positive for a bacterial pathogen were analyzed. The mean TTP was 15.4 hours and the median TTP was 13.0 hours. TTP did not vary by gender or Rochester risk stratification. TTP did not change significantly when 39 cultures that were positive only for common contaminants were removed from the analysis. By 24, 36, and 48 hours, 91%, 96%, and 99% of cultures were positive, respectively. Escherichia coli was the most prevalent species (41%), followed by Group B Streptococcus (22%), Staphylococcus aureus (5%), and Streptococcus pneumoniae (5%).The authors conclude that most pathogens in febrile bacteremic infants <91 days old will be identified within 24 hours of collection, and that 24 hours is an adequate observation period to detect most clinically significant bacteremia.Dr Garber 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.Pediatric hospitalists frequently care for young well-appearing infants with fever. Traditional practice is to risk stratify and perform cultures of blood, urine, and cerebrospinal fluid (CSF). While urinalysis and CSF indices can rule out urinary tract infection and meningitis, infants often remain hospitalized for 48 hours awaiting blood culture results.2 Automated continuously monitored blood culture systems which identify bacteria more quickly than manual methods, the changing epidemiology of bacteremia in infants, and decreases in bacteremia due to vaccinations and maternal intrapartum Group B Streptococcus prophylaxis have altered the risk:benefit ratio of this approach.Previously, an evidenced-based process model for managing well-appearing febrile infants under 91 days old was evaluated in a large system with 21 hospitals, and the results indicated that many infants can be discharged at 24 or 36 hours without adverse consequences (see AAP Grand Rounds, November 2012;28[5]:49).3 In the current study, the authors evaluated nationally representative data on TTP in an attempt to generalize those geographically limited efforts. Using the PRIS network, they obtained data from 17 hospital systems across all major regions of the United States. Their findings have the potential to increase quality and decrease costs of care for this common condition. Using current estimates of the incidence of bacteremia in this population, 0.9% to 2%,2 the authors calculate that 556 to 1,235 infants would need to be observed beyond 24 hours to capture 1 additional case of bacteremia, and that 1 of those infants would be predicted to acquire a nosocomial infection during the extra day of hospitalization.4The authors discuss important limitations: lack of urine/CSF TTP data, unknown volume of blood cultured and length of time from blood draw to analyzer placement, lack of clinical predictors for delayed culture growth, and unknown number of negative cultures. The authors did not address whether low numbers of cultures from 8 of the sites affect the generalizability of the results. Furthermore, hospitalists will need to become familiar with their laboratory’s monitoring procedures before adopting this strategy. Despite these limitations, the data may allow pediatric hospitalists to give parents of febrile infants a great gift – fewer nights in the hospital!

Prevalence of serious bacterial infections in return visits to the emergency department among infants aged 90 days or younger.

The main objective of this study was to describe the epidemiology of return visits (RVs) in well-appearing infants to an urban emergency department (ED) who were evaluated for serious bacterial infection (SBI) at their index ED visit. We conducted a retrospective chart review on infants aged 90 days and younger who were evaluated for SBI at their initial ED visit from 2003 through 2009. A parent database of all febrile infants evaluated for SBI was queried to identify patients who had an RV within 7 days of the index visit. We collected demographic variables including age, sex, and past medical history as well as laboratory test results including white blood cell count, blood, urine, and cerebrospinal fluid cultures and viral studies. Of eligible febrile infants, 10.8% (350/3220) had an RV to the ED within 7 days. The prevalence of SBI in the RV cohort was 6.0% (21/350), which included 1.7% (6/350) bacteremia, 3.7% (13/350) urinary tract infection, and 0.6% (2/350) combined urinary tract infection and bacteremia. The blood culture contamination rate was 88%. Infants aged 90 days or younger who are evaluated for SBI have high RV rates. A substantial number of RVs are due to contaminated blood cultures. Future studies should be conducted to identify predictors for false-positive blood cultures.