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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms. IMPACT: 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.

Following Birth Hospitalization: Invasive Bacterial Infections in Preterm Infants Aged 7-90 Days.

OBJECTIVE: To assess the incidence rate of invasive bacterial infections in preterm infants and compare invasive bacterial infection rates and pathogens between preterm and full-term infants at age 7-90 days. STUDY DESIGN: This is a retrospective cohort study of the incidence rate of invasive bacterial infections among all infants born at Kaiser Permanente Northern California (KPNC), with blood and cerebrospinal fluid cultures collected between 7 and 90 days of chronological age from outpatient clinics, from emergency departments, and in the first 24 hours of hospitalization presenting for care between January 1, 2005, and December 31, 2017. Incidence rates of invasive bacterial infection by chronological age and postmenstrual age (PMA) and pathogens were compared between preterm and full-term infants. RESULTS: Between January 1, 2005, and December 31, 2017, a total of 479 729 infants were born at KPNC, including 440 070 full-term infants and 39 659 preterm infants. There were 283 cases of bacteremia in 282 infants. The incidence rate of invasive bacterial infection was significantly higher for preterm infants compared with full-term infants. The highest incidence rates of invasive bacterial infection were in preterm infants at chronological age 7-28 days and/or 37-39 weeks PMA. There was a trend toward lower rates of invasive bacterial infection with increasing PMA in preterm infants aged 61-90 days. Preterm infants aged 29-60 days or at ≥40 weeks PMA and those aged 61-90 days or at ≥43 weeks PMA had a rate of invasive bacterial infection equivalent to the overall rate seen in full-term infants of the same chronological age group. The distribution of pathogens causing bacteremia and meningitis did not differ between preterm and full-term infants. CONCLUSION: PMA and chronological age together were more useful than either alone in informing the incidence rate of invasive bacterial infection in preterm infants during the first 90 days of life.

Foaming of Binary Mixtures: Link with the Nonlinear Behavior of Surface Tension in Asymmetric Mixtures.

The lifetimes of single bubbles or foams that are formed in mixtures of liquids can be several orders of magnitude larger than the ones formed in pure liquids. We recently demonstrated that this enhanced stability results from differences between bulk and interfacial concentrations in the mixture, which induce a thickness dependence of the surface tension in liquid films, and thus a stabilizing Marangoni effect. Concentration differences may be associated with nonlinear variations of surface tension with composition and we further investigate their link with foamability of binary mixtures. We show that, for asymmetric binary mixtures, that is, made of molecules of very different sizes, strong nonlinearities in surface tension can be measured, that are associated with large foam lifetimes. When the molecules that occupy the largest surface areas have the smallest surface tension, the surface tension of the mixture varies sublinearly with composition, reflecting an enrichment in this species at the interface with air, as classically reported in the literature. In contrast, when they exhibit the largest surface tension, superlinear variations of surface tension are observed, despite a similar enrichment. We discuss these variations in light of a simple thermodynamic model for ideal mixtures and we demonstrate why foam stability is enhanced for both sublinear and superlinear surface tension variations, thus, shedding new light on foamability without added surfactants.

Understanding Frothing of Liquid Mixtures: A Surfactantlike Effect at the Origin of Enhanced Liquid Film Lifetimes.

The formation of froth in mixtures of liquids is well documented, particularly in oil mixtures. However, in nonvolatile liquids and in the absence of surface-active molecules, the origin of increased liquid film lifetimes had not been identified. We suggest a stabilizing mechanism resulting from the nonlinear variations of the surface tension of a liquid mixture with its composition. We report on experimental lifetimes of froths in binary mixtures and show that their variations are well predicted by the suggested mechanism. We demonstrate that it prescribes the thickness reached by films before their slow drainage, a thickness which correlates well with froth lifetimes for both polar and nonpolar liquids.

Using AAP Guidelines for Managing Febrile Infants Without C-Reactive Protein and Procalcitonin.

BACKGROUND AND OBJECTIVES: In 2021, the American Academy of Pediatrics (AAP) published the Clinical Practice Guideline (CPG) for management of well-appearing, febrile infants 8 to 60 days old. For older infants, the guideline relies on several inflammatory markers, including tests not rapidly available in many settings like C-reactive protein (CRP) and procalcitonin (PCT). This study describes the performance of the AAP CPG for detecting invasive bacterial infections (IBI) without using CRP and PCT. METHODS: This retrospective cohort study included infants aged 8 to 60 days old presenting to Kaiser Permanente Northern California emergency departments between 2010 and 2019 with temperatures ≥38°C who met AAP CPG inclusion criteria and underwent complete blood counts, blood cultures, and urinalyses. Performance characteristics for detecting IBI were calculated for each age group. RESULTS: Among 1433 eligible infants, there were 57 (4.0%) bacteremia and 9 (0.6%) bacterial meningitis cases. Using absolute neutrophil count >5200/mm3 and temperature >38.5°C as inflammatory markers, 3 (5%) infants with IBI were misidentified. Sensitivities and specificities for detecting infants with IBIs in each age group were: 8 to 21 days: 100% (95% confidence interval [CI] 83.9%-100%) and 0% (95% CI 0%-1.4%); 22 to 28 days: 88.9% (95% CI 51.8%-99.7%) and 40.4% (95% CI 33.2%- 48.1%); and 29 to 60 days: 93.3% (95% CI 77.9%-99.2%) and 32.1% (95% CI 29.1%- 35.3%). Invasive interventions were recommended for 100% of infants aged 8 to 21 days; 58% to 100% of infants aged 22 to 28 days; and 0% to 69% of infants aged 29 to 60 days. CONCLUSIONS: When CRP and PCT are not available, the AAP CPG detected IBI in young, febrile infants with high sensitivity but low specificity.

Clinical management and outcomes for febrile infants 29-60 days evaluated in community emergency departments.

Objective: Describe emergency department (ED) management and patient outcomes for febrile infants 29-60 days of age who received a lumbar puncture (LP), with focus on timing of antibiotics and type of physician performing LP. Methods: Retrospective observational study of 35 California EDs from January 1, 2010 through December 31, 2019. Primary analysis was among patients with successful LP and primary outcome was hospital length of stay (LOS). Logistic regression analysis included variables associated with LOS of at least 2 days. Secondary outcomes were bacterial meningitis, hospital admission, length of antibiotics, and readmission. Results: Among 2569 febrile infants (median age 39 days), 667 underwent successful LP and 633 received intravenous antibiotics. Most infants (n = 559, 88.3%) had their LP before intravenous antibiotic administration. Pediatricians performed 54% of LPs and emergency physicians 34%. Sixteen infants (0.6% of 2569) were diagnosed with bacterial meningitis, and none died. Five hundred and fifty-eight (88%) infants receiving an LP were hospitalized. Among patients receiving an LP and antibiotics (n = 633), 6.5% were readmitted within 30 days. Patients receiving antibiotics before LP had a longer length of antibiotics (+ 7.9 hours, 95% confidence interval [CI] 3.8-13.4). Primary analysis found no association between timing of antibiotics and LOS (odds ratio [OR] 0.67, 95% CI 0.34-1.30), but shorter LOS when emergency physicians performed the LP (OR 0.66, 95% CI 0.45-0.97). Conclusions: Febrile infants in the ED had no deaths and few cases of bacterial meningitis. In community EDs, where a pediatrician is often not available, successful LP by emergency physician was associated with reduced inpatient LOS.

Roseville Protocol for the Management of Febrile Infants 7-60 Days.

OBJECTIVES: The Roseville Protocol modifies the Rochester Protocol by adding a high-risk temperature criterion of >38.5°C for infants 7 to 28 days old and by allowing febrile infants 29 to 60 days old with abnormal urinalysis but reassuring complete blood cell counts to be discharged home on oral antibiotics without receiving a lumbar puncture (LP). In this study, we define the Roseville Protocol test characteristics to detect invasive bacterial infection (IBI) and retrospectively compare its performance to that of the Rochester, Philadelphia, and Boston protocols. METHODS: In this retrospective study, we examine all cases of fever in infants aged 7 to 60 days presenting to a large health maintenance organization from 2007 to 2016 and having requisite laboratory tests for protocol analysis. The 4 protocols were retrospectively applied to this cohort to calculate each protocol's sensitivity and specificity to detect IBI. Protocols were compared regarding recommended LPs, admissions, and parenteral antibiotics. RESULTS: In 627 infants 7 to 28 days old, the Roseville Protocol had a sensitivity of 96.7% and a negative predictive value of 99.5%. It identified 2 IBIs missed by the Rochester Protocol but recommended an absolute increase of 19% in LPs and admissions. In 1176 infants 29 to 60 days old, the Roseville Protocol had a sensitivity of 91.4% and a negative predictive value of 99.6%. There was an absolute reduction in LPs by 18% to 44% compared to the Rochester Protocol and by 74% to 100% compared to the Philadelphia and Boston protocols. There was an absolute reduction in admissions by 18% to 44% compared to the Rochester Protocol, by 25% to 51% compared to the Philadelphia Protocol, and by 10% to 36% compared to the Boston Protocol. CONCLUSIONS: The Roseville Protocol has sensitivity and specificity comparable to that of existing protocols for IBI in febrile infants 7 to 60 days old, while allowing for fewer invasive procedures and hospitalizations in infants ≥29 days old.

The Prevalence of Bacterial Meningitis in Febrile Infants 29-60 Days With Positive Urinalysis.

OBJECTIVES: This study evaluates whether bacterial meningitis prevalence differs by urinalysis result and whether antibiotic treatment of presumed urinary tract infection without cerebrospinal fluid (CSF) culture produces adverse sequelae in febrile infants 29 to 60 days old. METHODS: This retrospective cohort study identified febrile infants 29 to 60 days old presenting to Kaiser Permanente Northern California sites from 2007 to 2015 who underwent urinalysis and blood, urine, and CSF cultures, comparing the prevalence of meningitis among infants with positive versus negative urinalysis results using a two 1-sided test for equivalence. Additionally, febrile infants treated with antibiotics for positive urinalysis results without CSF culture were identified and their charts were reviewed for adverse sequelae. RESULTS: Full evaluation was performed in 833 febrile infants (835 episodes). Three of 337 infants with positive urinalysis (0.9%; 95% confidence interval [CI]: 0.0%-1.9%) and 5 of 498 infants with negative urinalysis (1%; 95% CI: 0.1%-1.9%) had meningitis. These proportions were statistically equivalent within 1%, using two 1-sided test with a P value of .04. There were 341 febrile infants (345 episodes) with positive urinalysis treated with antibiotics without lumbar puncture. Zero cases of missed bacterial meningitis were identified (95% CI: 0%-1.1%). Zero cases of severe sequelae (sepsis, seizure, neurologic deficit, intubation, PICU admission, death) were identified (95% CI: 0%-1.1%). CONCLUSIONS: The prevalence of bacterial meningitis does not differ by urinalysis in febrile infants 29 to 60 days old. Antibiotic treatment of infants with positive results for urinalysis without lumbar puncture may be safe in selected cases.

Kinetics of DNA alkylation, depurination and hydrolysis of anti diol epoxide of benzo(a)pyrene and the effect of cadmium on DNA alkylation.

Anti benzo[a]pyrene diol epoxide (BPDE) alkylates guanines of DNA at N7 in the major groove and at the exocyclic amino group in the minor groove. In this report we investigated the rates of BPDE hydrolysis, DNA alkylation and subsequent depurination of BPDE-adducted pBR322 DNA fragment using polyacrylamide gel electrophoresis. Preincubation studies showed that it hydrolyzed completely in triethanolamine buffer in <2 min. The depurination kinetics showed that a fraction of the N7 alkylated guanine depurinated rapidly; however a significant amount of N7 guanine alkylation remained stable to spontaneous depurination over a 4-h period. Similar results were obtained for the hydrolysis and alkylation rates of syn isomer but it required nearly 500 times more concentration to induce similar levels of N7 guanine alkylation. Cadmium ion strongly inhibited the N7 guanine alkylation of both isomers. But the minor groove alkylation was not affected as demonstrated by postlabeling assay which confirmed the presence of heat-and cadmium-stable minor groove adducts in BPDE-treated calf thymus DNA. Based on these and our earlier findings, we propose a mechanism for the synergistic effect of cadmium in chemically induced carcinogenesis.