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Dating back to 2011, practice guidelines considered Black race a factor associated with lower risk of urinary tract infection (UTI). Race-based clinical decisions raise concerns about potential treatment disparities. We investigate urine testing (urinalysis and/or urine culture) among young febrile children in the emergency department (ED), revisits, and potential missed diagnoses by race/ethnicity. We performed a multicenter retrospective cohort study of children 2–24 months evaluated in 26 US EDs from 2009 to 2019 with a fever diagnosis. We evaluated longitudinal testing trends, constructed a generalized linear mixed-effects model to identify the association of race/ethnicity with testing, and characterized UTI diagnoses and ≤ 7-day revisits. Of 734,730 included patients, 24.1% were Black. Variation in urine testing was observed by patient race/ethnicity (23.4% Black, 31.7% White, 33.9% Hispanic, 30.0% other race). Relative differences in testing persisted over time. Black patients had lower adjusted odds of testing (0.70, 95% confidence interval [CI] 0.69–0.71). Among patients with urine testing, 2.4% (95% CI 2.3–2.6%) of Black and 3.3% (95% CI 3.1–3.4%) of White patients were diagnosed with UTI. Among Black patients with urine testing on the index visit, 8.5% (95% CI 8.2–8.8%) had return visits compared to 7.6% (95% CI 7.5–7.8%) among those without urine testing on index visit. Among patients with urine testing on revisit, UTI diagnosis was similar by race/ethnicity. Black patients had lower rates of urine testing and UTI diagnoses relative to other racial/ethnic groups. This was not associated with higher rates of missed diagnoses or unscheduled return visits.

The microbial ecosystem within the bladder that can be measured within the urine, or urobiome, is an emerging field of study with little published data regarding children. However, investigations into urobiome research have the potential to significantly impact the understanding of the pathophysiology of genitourinary conditions, as well as potentially identify novel therapeutics. Therefore, both researchers and clinicians should be aware of pediatric urobiome research. The purpose of this review is to highlight the literature around urobiome research in urinary tract infections, nephrolithiasis, and neurogenic bladder; comment on pediatric-specific considerations when reading and interpreting the urobiome literature; and to identify new potential areas of research.

To compare clinical history and measurements of fecal load on abdominal radiography (AR) in the prediction of urinary tract infection (UTI) recurrence in children. We combined data from two multicenter longitudinal studies in which children less than 6 years of age with a first or second UTI were followed for recurrence of UTI. Two radiologists reviewed the scout abdominal radiographs of initial voiding cystourethrograms obtained at enrollment from children at two participating sites and measured stool visible in various parts of the colon. We examined how well clinical variables (e.g., voiding and bowel history, use of laxatives at enrollment) and measurements of fecal load predicted recurrence of UTI within 12 months of enrollment. One hundred and ninety-two children were included. On univariate analyses, age, vesicoureteral reflux (VUR), cecal diameter, rectal diameter, and total stool length on AR were associated with recurrence of UTI. After controlling for age, the odds of recurrent UTI in children with VUR at baseline was 3.85 (95% CI: 1.62, 9.14) higher than in children without VUR. Recurrent UTI was 2.57 (95% CI: 1.01, 6.55) times more likely in children with cecal diameter > 3.10 cm than children with lower cecal diameters; time to first recurrent UTI was shorter in children with elevated cecal diameters (p = 0.0023). Cecal diameter on abdominal radiographs predicts UTI recurrence in children with a previous UTI. However, its accuracy is suboptimal to serve as a screening test. Accordingly, its routine use for this indication is not supported. If cecal diameter on an AR ordered for another indication is > 3.10 cm, then management of constipation could be considered.

BACKGROUND Acute otitis media (AOM) is the most frequent reason for children to be prescribed antimicrobial treatment. Surfactants are naturally occurring substances that may restore the eustachian tube’s function and potentially enhance resolution of AOM. METHODS This was a phase 2a, single-center, double-blind, randomized, placebo-controlled, parallel group clinical trial to assess safety, tolerability, and efficacy of 20 mg per day intranasal OP0201 as an adjunct therapy to oral antimicrobial agents for treating AOM in young children. We randomly assigned 103 children aged 6 to 24 months with AOM to receive either OP0201 or placebo twice daily for 10 days. All children received amoxicillin-clavulanate 90/6.4 mg/kg per day in 2 divided doses for 10 days. Participants were managed for up to 1 month. Postrandomization visits occurred between days 4 and 6 (visit 2), days 12 and 14 (visit 3), and days 26 and 30 (visit 4). Primary efficacy endpoints were resolution of a bulging tympanic membrane at visit 2 and resolution of middle-ear effusion at visit 3. RESULTS No clinically meaningful differences between treatment groups were apparent for primary or secondary endpoints. There were no safety concerns identified. CONCLUSIONS In young children with AOM, intranasally administered surfactant (OP0201) did not improve clinical outcomes. Further research may be warranted among children with persistent middle-ear effusion.

* Abbreviations: CI — : confidence interval COVID-19 — : coronavirus disease 2019 PCR — : polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Abbott BinaxNOW (a bedside lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen) is widely available under US Food and Drug Administration emergency use authorization for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic patients within 7 days of symptom onset. Its diagnostic performance in symptomatic children has not been evaluated. Cross-sectional study of symptomatic children ≤20 years presenting for care to 1 of 2 primary care practices in December 2020, during which time coronavirus disease 2019 (COVID-19) rates were … Address correspondence to Nader Shaikh, MD, MPH, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 1 Children’s Hospital Dr, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: nader.shaikh{at}chp.edu

BACKGROUND: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media. METHODS: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period. RESULTS: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children’s cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial. CONCLUSIONS: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.)

Objective To modify a parent-reported scale we developed to follow symptoms of young children with acute otitis media (AOM-SOS) with the aim of improving its psychometric properties. Study design We modified version 4.0 of the scale by increasing the number of response options from 3 to 6. We compared the distribution of scores, internal reliability, construct validity, and responsiveness of versions 4.0 and 5.0 in children diagnosed with acute otitis media (AOM) in 2 studies. For Version 5.0, we also estimated the minimal important difference (MID) and assessed its construct validity. Results 291 and 70 children were enrolled in the studies evaluating version 4.0 and 5.0, respectively. Version 5.0 had fewer items at the ceiling and better psychometric properties (responsiveness, internal reliability, and test-retest reliability). Changes in the score for Version 5.0 corresponded to changes in clinical status. Factor analysis supported a one-factor solution. Children whose parents reported only a small degree of improvement on the diary (compared to the day before) had a mean decrease in AOM-SOS score of approximately 20%. This value can be used as the MID for this version of the scale. Conclusions Modification of the AOM-SOS improved its psychometric properties. Data presented here support the use of Version 5.0 of the AOM-SOS as a measure of change in symptom burden in clinical trials of children with acute otitis media.

The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI.This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls.We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children.NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI.ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long‐term renal sequelae. If non‐invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow‐up could potentially be individualized. This is an update of a review first published in 2015. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin (PCT), C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews through to 17th December 2019 for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (PCT, CRP, ESR) against the results of an acute‐phase (99)Tc‐dimercaptosuccinic acid (DMSA) scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture‐confirmed episode of UTI. The following cut‐off values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/hour for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random‐effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 36 studies met our inclusion criteria. Twenty‐five studies provided data for the primary analysis: 12 studies (1000 children) included data on PCT, 16 studies (1895 children) included data on CRP, and eight studies (1910 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the PCT, CRP, ESR tests at the aforementioned cut‐offs were 0.81 (0.67 to 0.90), 0.93 (0.86 to 0.96), and 0.83 (0.71 to 0.91), respectively. The summary specificity values for PCT, CRP, and ESR tests at these cut‐offs were 0.76 (0.66 to 0.84), 0.37 (0.24 to 0.53), and 0.57 (0.41 to 0.72), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

A state-of-the art review of current literature on UTI in children, with a particular focus on its diagnosis and management by general pediatricians. Urinary tract infection (UTI) is common in children, and girls are at a significantly higher risk, as compared to boys, except in early infancy. Most cases are caused by Escherichia coli. Collection of an uncontaminated urine specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated cases that respond well to the treatment. A renal ultrasound examination is advised in all young children with first febrile UTI and in older children with recurrent UTI. Most children with first febrile UTI do not need a voiding cystourethrogram; it may be considered after the first UTI in children with abnormal renal and bladder ultrasound examination or a UTI caused by atypical pathogen, complex clinical course, or known renal scarring. Long-term antibiotic prophylaxis is used selectively in high-risk patients. Few patients diagnosed with vesicoureteral reflux after a UTI need surgical correction. The most consequential long-term complication of acute pyelonephritis is renal scarring, which may increase the risk of hypertension or chronic kidney disease later in life. Treatment of acute pyelonephritis with an appropriate antibiotic within 48 hours of fever onset and prevention of recurrent UTI lowers the risk of renal scarring. Pathogens causing UTI are increasingly becoming resistant to commonly used antibiotics, and their indiscriminate use in doubtful cases of UTI must be discouraged.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged

Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media.We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms.Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P0.001).Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .).

BACKGROUND: A recent study in young infants found that different cutoffs maximized the accuracy of the urine white blood cell count in dilute versus concentrated urine samples. We aimed to confirm this finding and to determine its impact on clinical care. METHODS: We conducted a retrospective analysis of data gathered on consecutive children RESULTS: We included 10 078 children. The ability to rule in UTI (as measured by the positive likelihood ratio [LR]) was similar in dilute and concentrated urine for the leukocyte esterase test (11.76 vs 10.71, respectively). The positive LR for urine white blood cell count per high-powered field was higher in dilute urine (9.83 vs 6.12). In contrast, the positive LR for the nitrite test was lower in dilute urine (20.54 vs 47.44). Despite these differences, we found little change in the number of children treated with antibiotics in predictive models that took urine SG into consideration. CONCLUSIONS: Although we found that urine SG influences the accuracy of some components of the urinalysis, its inclusion in the decision-making process had negligible effect on the clinical care of children with UTI.

Vesicoureteral reflux (VUR) is a complex, heritable disorder. Genome-wide linkage analyses of families affected by VUR have revealed multiple genomic loci linked to VUR. These loci normally harbor a number of genes whose biologically functional variant is yet to be identified. DNA copy number variations (CNVs) have not been extensively studied at high resolution in VUR patients. In this study, we performed array comparative genomic hybridization (aCGH) on a cohort of patients with a history of both VUR and urinary tract infection (UTI) with the objective of identifying genetic variations responsible for VUR and/or UTI susceptibility. UTI/VUR-associated CNVs were identified by aCGH results from the 192 Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) patients compared to 683 controls. Rare, large CNVs that are likely pathogenic and lead to VUR development were identified using stringent analysis criteria. Because UTI is a common affliction with multiple risk factors, we utilized standard analysis to identify potential disease-modifying CNVs that can contribute to UTI risk. Gene ontology analysis identified that CNVs in innate immunity and development genes were enriched in RIVUR patients. CNVs affecting innate immune genes may contribute to UTI susceptibility in VUR patients and may provide the first step in assisting clinical medicine in determining adverse outcome risk in children with VUR.

Urinary tract infections (UTIs) in children are among the most common bacterial infections in childhood. They are equally common in boys and girls during the first year of life and become more common in girls after the first year of life. Dividing UTIs into three categories; febrile upper UTI (acute pyelonephritis), lower UTI (cystitis), and asymptomatic bacteriuria, is useful for numerous reasons, mainly because it helps to understand the pathophysiology of the infection. A single episode of febrile UTI is often caused by a virulent Escherichia coli strain, whereas recurrent infections and asymptomatic bacteriuria commonly result from urinary tract malformations or bladder disturbances. Treatment of an upper UTI needs to be broad and last for 10 days, a lower UTI only needs to be treated for 3 days, often with a narrow-spectrum antibiotic, and asymptomatic bacteriuria is best left untreated. Investigations of atypical and recurrent episodes of febrile UTI should focus on urinary tract abnormalities, whereas in cases of cystitis and asymptomatic bacteriuria the focus should be on bladder function.

Objectives: To gather preliminary data on the effectiveness and feasibility of cerumen removal using three irrigation methods and a metal curette in young children. Study design: Pilot study conducted as a randomized clinical trial of well and ill children age 6 months to 6 years with ≥25% cerumen occlusion in at least one ear. Children were stratified by age and randomized to one of four methods of cerumen removal: syringe with attached angiocath tubing, Elephant Ear Washer Bottle System®, OtoClear® Spray Wash Kit, or metal curette. Clinicians, blinded from treatment assignment, assessed the degree of cerumen occlusion before and after the procedure. Outcomes included reduction in cerumen occlusion, successful removal, time until completion and parental satisfaction. Rules for stopping procedures were established a priori. Results: Thirty-eight children underwent procedures (59 ears). There were no significant differences in reduction in cerumen and successful removal among the methods. Overall, 36 (61%) of 59 of procedures were successful. The syringe with angiocath tubing took the most time (P = 0.04) and resulted in the most stopped procedures (P < 0.01). Parental satisfaction scores were not significantly different. Conclusions: Irrigation methods performed comparably to cerumen removal with curette; the SA method had drawbacks. Irrigation can be performed by non-clinicians, which is potentially a significant advantage. (Clinical trial registration: http://www.isrctn.com/ISRCTN74402562).

Background The AAP recommends 7 to 14-days of antimicrobials for the treatment of urinary tract infections (UTIs), one of the most common bacterial infections of childhood. However, most physicians routinely prescribe at least 10 days of therapy. Prior observational studies suggest that courses shorter than 10 days might be effective. Methods The primary objective was to determine if halting antimicrobial therapy in children who improved clinically after 5 days of therapy (short course therapy) results in a similar failure rate as children who continue antimicrobials for an additional 5 days (standard course therapy). This was a multi-center, randomized, double-blind, placebo-controlled non-inferiority clinical trial of children ages 2 to 10 years with UTI. Subjects treated with 1 of 5 antibiotics (trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, cefixime, cefdinir or cephalexin) were eligible. Children were stratified by presence or absence of fever and were enrolled if they had clinical improvement before Day 5 of treatment. The a priori equivalence interval was set at 0.05 for a one-sided analysis. The primary outcome was development of a symptomatic UTI defined as the presence of symptoms, pyuria, and a positive urine culture. The Intent-to-Treat population included children who took at least one dose of study medication. Results A total of 693 children were randomized, 345 to short course and 348 to standard course. Median age was 4 years old (IQR; 2-6), 652 (96.3%) were female and 255 were febrile (37%). Treatment success rate was 322/336 (96%) for short course and 326/328 (99%) for standard course. The 95% upper CI limit for the difference was 0.054. Treatment failure was not related to age group, fever at presentation, antibiotic type, or study site. There were no significant differences between groups the in the rates of adverse events, recurrent infection, clinical symptoms that may have been related to UTI, or emergent antibiotic resistance. Conclusion In children aged 2 months to 10 years with UTI, halting antimicrobial therapy in children who had exhibited clinical improvement after 5 days and continuing for an additional 5 days both resulted in high success rates. However, short course was inferior to treatment for 10 days. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support) Brian T. Fisher, DO, MPH, MSCE, Astellas (Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support)

Objective To determine the point prevalence of bacteriuria and bacteriuria without pyuria in asymptomatic children by a systematic review of the literature. Study design We searched MEDLINE and EMBASE for English-, French-, German-, Italian-, and Spanish-language articles. We included articles reporting data on bacteriuria in asymptomatic children up to 19 years of age who had urine collected by suprapubic bladder aspiration, bladder catheterization, or by 3 consecutive clean catch samples. Two independent reviewers assessed studies for inclusion and abstracted data. Results Fourteen studies (49 806 children) were included. The prevalence of asymptomatic bacteriuria was 0.37% (95% CI, 0.09-0.82) in boys and 0.47% (95% CI, 0.36-0.59) in girls. The corresponding values for asymptomatic bacteriuria without pyuria were 0.18% (95% CI, 0.02-0.51) and 0.38% (95% CI, 0.22-0.58), respectively. The subgroups with the highest prevalence of asymptomatic bacteriuria were uncircumcised males 2 years of age. In males, the prevalence of asymptomatic bacteriuria after infancy was 0.08% (95% CI, 0.01-0.37). The median duration of asymptomatic bacteriuria in untreated boys and girls, from the one study reporting this outcome, was 1.5 and 2 months, respectively. Conclusions Some clinicians are concerned that when a preverbal child with asymptomatic bacteriuria develops a nonlocalizing febrile illness and presents for evaluation, they may be mistakenly diagnosed as having a urinary tract infection (UTI). Given that the prevalence of asymptomatic bacteriuria is considerably lower than the prevalence of UTI in most subgroups examined, this will occur extremely rarely. These data suggest that the current definition of UTI should be revisited.

We aimed to determine which children are prone to non-Escherichia coli urinary tract infection (UTIs). We included 769 children with UTI. We found that circumcised males, Hispanic children, children without fever and children with grades 3 and 4 vesicoureteral reflux were more likely to have a UTI caused by organisms other than E. coli. This information may guide clinicians in their choice of antimicrobial therapy.

Objectives To identify factors associated with delayed antimicrobial treatment in febrile children with urinary tract infection (UTI). Study design We reviewed data from 802 children with UTI enrolled in 2 previously conducted prospective studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) and extracted data on possible predictors of delayed treatment including age, sex, history of UTI, ethnicity, race, primary caregiver's education level, insurance, and income. We used univariate and multivariable analyses to investigate the relationship between these predictors and treatment delay. Results We included 660 febrile patients with a mean age of 17.0 months old. Older age and commercial insurance were associated with delayed treatment on univariate analysis. Compared with younger children, treatment was delayed by an average of 26.2 hours in children ≥12 months of age. This relationship remained significant on multivariable analysis. Treatment also was delayed by an average of 12.6 hours in patients with commercial insurance. Race, ethnicity, primary caregiver's education level, and income were not associated with delayed treatment. Conclusions Older age was a consistent predictor of delayed antimicrobial treatment. Delays in the initiation of antimicrobial therapy for UTI has previously been associated with renal scarring. Educating parents with older children regarding the management of fever as well as providers regarding prompt evaluation and management may help to reduce renal scarring.

Objective To characterize the incidence of adverse events (AEs) associated with antibiotics used to treat acute otitis media in children. Study design We searched MEDLINE for studies conducted between January 1, 1966, and August 25, 2018. Two authors independently assessed potential studies and extracted the data. We included published randomized controlled trials, cross-sectional studies, and cohort studies that evaluated the incidence of diarrhea, generalized rash, diaper rash, and candidal diaper dermatitis associated with the use of amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir, and placebo in children with acute otitis media. Results We included 82 studies in the meta-analysis. The incidence of diarrhea, listed from lowest to highest, was azithromycin (2.2%), placebo (6.9%), low-dose amoxicillin (8.7%), cefdinir (13.0%), high-dose amoxicillin (13.8%), and high-dose amoxicillin/clavulanate (18.9%). The incidence of generalized rash, listed from lowest to highest, was azithromycin (1.4%), placebo (2.3%), low-dose amoxicillin (2.9%), high-dose amoxicillin/clavulanate (4.9%), and high-dose amoxicillin (6.5%). In studies of low-dose amoxicillin, we found a higher incidence of diarrhea in studies that used daily diaries to collect information about diarrhea and a lower incidence of generalized rash in studies that reported only rashes judged to be secondary to antibiotic use. Conclusions The incidence of AEs varies widely depending on which antibiotic is used and how the information on AEs was collected or reported. The AEs rates reported here may be helpful to clinicians when choosing an antibiotic to treat acute otitis media.

Objective Urinary tract infection (UTI) is among the most common infection diseases in children with nephrotic syndrome (NS), resulting in treatment failure and relapse. No systematic reviews have estimated the prevalence of UTI in children with NS on a global scale, therefore, did the first systematic review and meta-analysis study to estimate the prevalence of UTI in children with NS in different geographical regions and different countries. Methods PubMed, EMBASE, Scopus, Web of Science and Google Scholar databases were systematically searched up to 20 February 2019, for studies assessing the prevalence of UTI in children with NS. Pooled prevalence of UTI was calculated using the random effects model. Data were stratified based on WHO geographical regions and individual countries. Subgroup analysis regarding the gender and socio-demographic variables were also performed. Results Thirty studies involving 6314 children with NS were included. The pooled prevalence of UTI was 21.6% (95%CI, 17.1–26.5%), with the highest prevalence in the African region (34.8%, 95%CI: 4.7–73.9%), and lowest prevalence in the region of the Americas (7.4%, 95% CI: 1.7–16.2%). With respect to countries, the lowest and highest prevalence rates were reported from USA (3.3%) and Indonesia (45.9%). In subgroup analyses, a higher prevalence was observed in females, and in countries with lower levels of income and human development index. The most common isolated bacteria were Escherichia coli (28%), and Klebsiella spp. (22.4%). Conclusions The high prevalence of UTI in children with NS reported in this study is a significant health threat for these patients. These results call for intervention strategies and preventive measures for children with NS to reduce the burden of UTI.

Paired nasopharynx and midturbinate swabs were obtained from 96 children (mean age: 2.45 years) with upper respiratory tract symptoms. Of these, 38.5% were colonized with Streptococcus pneumoniae only, 16.7% with Haemophilus influenzae only and 9.4% with both bacteria. Bacterial cultures from paired nasopharynx and midturbinate swabs demonstrated agreement for S. pneumoniae (κ = 0.75), H. influenzae (κ = 0.59) and for both pathogens (κ = 0.62). This report compares the results of bacterial cultures obtained from the nasopharynx and midturbinate specimens in children with upper respiratory tract infections.

Reporting of harms in randomized control trials is often inconsistent and inadequate. To assess the quality of harms reporting in randomized control trials evaluating the efficacy of antibiotics used to treat pediatric acute otitis media and to investigate whether connections to pharmaceutical companies or the publication of the CONSORT-Harms extension influenced the quality of harms reporting. We considered randomized control trials that evaluated the efficacy and safety of antibiotic treatment for uncomplicated acute otitis media in children aged 0–19. We evaluated the quality of harms reporting using a 19-item checklist addressing the recommendations endorsed in the CONSORT-Harms extension. 160 studies met our inclusion criteria. Overall quality of reporting relating to harms was low; on average studies adhered to 55.2% of the checklist items on the quality of harms reporting. The reporting of methods relating the measurement of harms was particularly lacking; studies adhered to an average of only 33.2% of the checklist items. The overall quality of reporting did not change after the publication of the CONSORT-Harms extension. The overall quality of reporting did not differ significantly in reports with or without declared connections to pharmaceutical companies (mean quality score of 56.8% vs 52.0%, respectively). Harms reporting in pediatric randomized trials, especially the reporting of methods used to collect harms data, remains inadequate.

BACKGROUND: A recent study revealed that specific uropathogens are associated with lower odds of pyuria in a general pediatrics population. Children with neurogenic bladders who require clean intermittent catheterization (CIC) frequently have pyuria. Our objective with this study was to determine if an association exists between pyuria and type of uropathogen in CIC-dependent children. METHODS: We obtained urinalysis and urine culture results from electronic medical records from January 2008 through December 2014 for patients ≤18 years of age with neurogenic bladders managed at a single institution. Cultures without concurrent urinalyses were excluded from analysis, as were cultures that yielded no growth, fungal growth, or growth of unidentified mixed organisms. We used logistic regression to determine the association of pyuria and leukocyte esterase with specific uropathogens. RESULTS: We included 2420 cultures in this analysis. The growth of Enterococcus on urine culture was associated with lower odds of both pyuria and leukocyte esterase. In contrast, the growth of more than 100 000 colony-forming units per milliliter of Proteus mirabilis was associated with increased odds of both pyuria and leukocyte esterase, and the growth of Pseudomonas aeruginosa was associated with increased odds of leukocyte esterase but not pyuria. Certain etiologies of neurogenic bladder, such as bladder exstrophy and cloacal malformations, were also associated with increased odds of pyuria compared with neurogenic bladder due to myelomeningocele. CONCLUSIONS: In children with neurogenic bladders who require CIC, Enterococcus may grow in urine culture without pyuria or positive leukocyte esterase. Accordingly, urine cultures should be obtained in symptomatic children, regardless of urinalysis results.

BackgroundIn children with acute otitis media (AOM), a decrease in nasopharyngeal (NP) colonization with vaccine serotypes of Streptococcus pneumoniae has been noted since the introduction of pneumococcal conjugate vaccines (PCVs). The purpose of this study is to describe corresponding changes in colonization with Haemophilus influenzae.MethodsIn 4 separate studies, we obtained NP cultures from children aged 6–23 months presenting with AOM. Cohort 1 was recruited before routine use of PCV7 (1999–2000); 93% of children in cohort 2 (2003–2005) and 100% in cohort 3 (2006–2009) received ≥2 doses of PCV7. All children in cohort 4 (2012–2014) received ≥2 doses of PCV13. Isolates of H. influenzae were tested for ß-lactamase production; ß-lactamase negative isolates from cohorts 3 and 4 underwent susceptibility testing.ResultsA total of 899 children were evaluated. NP colonization with H. influenzae was found in 26% of children in cohort 1 (n = 175), 41% in cohort 2 (n = 87), 33% in cohort 3 (n = 282), and 29% in cohort 4 (n = 355). Colonization with H. influenzae increased initially from cohort 1 to cohort 2 (P = .01), then decreased across cohorts 2, 3, and 4 (P = .03, test for trend). The prevalence rates of ß-lactamase production were 27%, 42%, 33%, and 30% in each of the 4 cohorts, respectively (P = .50).ConclusionsAlthough an initial increase in H. influenzae colonization was observed, suggesting an impact of PCVs, the most recent prevalence rates of NP colonization with H. influenzae and ß-lactamase production were like those observed before universal administration of PCV7. This knowledge is critical to guide appropriate treatment recommendations for children with AOM.

Chylothorax is defined as the accumulation of chyle within the pleural space. Originally described in 1917 by Pisek, it is the most common cause of pleural effusion in the neonatal period. The leading cause of chylothorax is laceration of the thoracic duct during surgery, which occurs in 0.85% to 6.6% of children undergoing cardiothoracic surgery. Few authors of reports in the literature have looked at etilefrine, a relatively unknown sympathomimetic, as an option for the medical treatment of chylothorax. In this case report, we review the clinical course of 2 infants with type III esophageal atresia who developed chylothorax after thoracic surgery and were successfully treated with intravenous etilefrine after failing initial dietary and pharmacological management.

OBJECTIVES:To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.METHODS:This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring.RESULTS:Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09–3.93]) and presence of renal scarring on the baseline 99mTc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22–6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86–4.87]).CONCLUSIONS:VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.

Objective This review aims to determine the effectiveness of low-dose transdermal estrogen versus placebo in postmenopausal women with moderate to severe hot flashes. Methods We conducted a systematic review of studies by searching Medline and EMBASE using the following inclusion criteria: double-blind, placebo-controlled, randomized controlled trials conducted in postmenopausal women with at least 7 hot flashes per day and/or at least 50 hot flashes per week. All included studies used estrogen formulations below the equivalent dose of 0.05 mg of 17β-estradiol. Results Nine studies met all inclusion criteria. Seven of nine studies had low risk of bias, whereas two studies had high risk of bias. Low-dose transdermal estrogen in all dose ranges was more likely than placebo to decrease the daily number of hot flashes. Meta-analysis was not performed as only three of the nine studies included measures of variance; weighted means were used to summarize the data. Results were divided into three groups by decreasing estrogen dose range (0.037-0.045, 0.020-0.029, and 0.003-0.125 mg). The mean daily decrease in the number of hot flashes from baseline was 9.36, 7.91, and 7.07, respectively. The mean daily decrease in the placebo groups was 5.07. Eight of the nine studies reported P values comparing each estrogen dose to placebo; all were significant at P Conclusions Although publication bias cannot be excluded, risk of bias and heterogeneity among studies are low. There is strong evidence to conclude that low-dose transdermal estrogen at any dose is more effective than placebo in decreasing the daily number of moderate to severe hot flashes.

Surveillance of children with acute otitis media (AOM) for nasopharyngeal colonization with Streptococcus pneumoniae before, during and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) indicated the near-complete elimination of PCV7 strains and the emergence of pneumococcal serotype 19A.To determine effects of the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal nasopharyngeal colonization, we obtained nasopharyngeal cultures from 228 children 6 through 23 of age months presenting with a new episode of AOM during 2012 and 2013 and enrolled in an ongoing clinical trial of antimicrobial efficacy. All children had received at least 2 doses of PCV13. The S. pneumoniae isolates were subjected to serotyping and testing for antimicrobial susceptibility. We compared the findings with results obtained in 3 earlier studies.We found nasopharyngeal colonization with S. pneumoniae in 113 (50%) of the children with AOM. PCV7 and PCV13 serotypes accounted for 2% and 12%, respectively, of the pneumococcal isolates. Of the 14 PCV13 isolates, 8 were serotype 19A. Nonvaccine serotypes accounted for 69% of the isolates. Most frequently occurring were subtypes of serotype 15 (23%) and serotype 35B (9%). Overall, 33% of the isolates were penicillin nonsusceptible, a proportion not significantly different from proportions found in our 3 earlier studies (26%, 36% and 37%, respectively). Serotypes 15 and 35B accounted for 51% of penicillin-nonsusceptible isolates.Expansion of contents of pneumococcal vaccine administered to children is followed by not-fully-predictable changes in nasopharyngeal pneumococcal colonization. Continued surveillance is required to help inform future vaccine development.

The authors administered a written survey consisting of colour images of 28 tympanic membranes (TM) to four groups of examiners: 86 medical students, 68 paediatric residents, 62 paediatricians and seven expert otoscopists. For each image, examiners were asked to indicate whether redness or bulging of the TM was present and to assign a diagnosis. The odds of diagnosing acute otitis media (AOM) was examined according to perceived redness or bulging of the TM. Medical students and paediatricians attributed approximately equal importance to isolated redness and isolated bulging of the TM. In contrast, experts placed significantly greater importance on isolated bulging of the TM compared with isolated redness of the TM. The authors suggest that training curricula emphasize the strong association between a bulging TM and a diagnosis of AOM, while de-emphasizing the association between TM redness and AOM.Les auteurs ont demandé à quatre groupes d’examinateurs de remplir un sondage écrit composé d’images couleur de 28 tympans. Ces groupes se composaient de 86 étudiants en médecine, 68 résidents en pédiatrie, 62 pédiatres et sept spécialistes de l’otoscopie. Pour chaque image, ils étaient invités à indiquer s’ils observaient une rougeur ou un bombement du tympan et à poser un diagnostic. Les auteurs ont examiné la possibilité de diagnostiquer une otite moyenne aiguë (OMA) selon la rougeur ou le bombement perçu du tympan. Les étudiants en médecine et les pédiatres attribuaient environ autant d’importance à une douleur isolée qu’à un bombement isolé. En revanche, les spécialistes accordaient beaucoup plus d’importance à un bombement isolé du tympan qu’à une rougeur du tympan. Les auteurs proposent que, dans le cursus d’enseignement, les professeurs soulignent l’association importante entre le bombement du tympan et un diagnostic d’OMA, mais atténuent l’association entre la rougeur du tympan et l’OMA.

Objectives: Data suggest that adolescents in the United States receive inadequate contraceptive counseling. This study sought to determine factors affecting pediatricians’ discussion of contraception with adolescent patients, with a specific focus on long-acting reversible contraception—implantable contraception and intrauterine devices. Methods: A cross-sectional survey was sent via email to a convenience sample of pediatric residents and pediatric primary care providers in Western Pennsylvania. Self-reported contraceptive counseling and prescribing practices in response to clinical vignettes were assessed. Results: Of potential participants (287), 88 (31%) responded. Younger providers and providers who had received contraceptive training were significantly more likely to discuss long-acting reversible contraception methods. Discussion of contraceptive methods also varied by both the age and the sexual history of the patient. Conclusion: Variation in contraceptive counseling potentially results in missed opportunities to counsel about and provide the most effective contraceptive methods. More uniform, universal provider training might alleviate some of these inconsistencies.

We thank Dr Schroeder for his comments on our article. We agree with Dr Schroeder that some children may have bacteriuria even when they are asymptomatic. We disagree, however, on the prevalence and clinical implications of this finding. Schroeder states that 1.4% of children have asymptomatic bacteriuria, and because the prevalence of urinary tract infection (UTI) among those tested is low (∼5%), a large proportion of children with apparent UTIs actually may have asymptomatic bacteriuria and are therefore being misdiagnosed. However, closer reading of the original articles describing the asymptomatic bacteriuria (by using a method of urine collection less prone to contamination, such as suprapubic aspiration), show that the 1.4% number is the period prevalence of asymptomatic bacteriuria (cumulative over the 12-month follow-up period).1 At any 1 point in time after 1 month of age, only 0% to 0.4% (see Fig 3 in the article by Wettergren et … E-mail: shaikhnader{at}gmail.com

Background and objectives An estimated 400,000 urinary tract infections (UTIs) are diagnosed annually in children aged 50% of febrile UTIs may be missed in this population. Here, we explored possible barriers to diagnosing febrile UTIs in very young children through social research of community pediatricians. Methods Following qualitative interviews, a quantitative survey was developed that included a high-risk case for febrile UTI, presented before prompting for the topic of the survey, to gauge practice of delayed testing. Factors associated with delay were explored using univariate logistic regression. The final survey link was sent to three populations via email, with the largest response from a survey sent to pediatricians in Pennsylvania, which formed the basis of our primary results. Results Of the 218 evaluable responses, 59.6% of physicians would initially test urine in the high-risk case patient, while 21.6% would choose to continue fever reducer and follow-up in 2 days. In the knowledge-based questions, 67.5, 34.0, and 35.6% of respondents identified the correct prevalences in total population, Caucasian girls, and uncircumcised boys, respectively. Many pediatricians (59.5%) believed that delays in detection are common in clinical practice. Physicians who chose to delay testing were more likely to be female, in practice for

Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively ( P = 0.10). The corresponding rates of diaper dermatitis were 21% and 33% ( P = 0.04) and of AOM treatment failure were 12% and 16% ( P = 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.)

Urinary tract infections (UTIs) represent a significant cause of serious bacterial infection in the pediatric population. Recently there has been much discussion surrounding the screening and diagnosis of UTIs. The American Academy of Pediatrics 2011 guidelines1 recommend suprapubic aspiration or catheterization in patients who cannot spontaneously void. Lavelle et al2 recently proposed a 2-step approach for the … E-mail: elaine.chiang{at}chp.edu

Background Urinary tract infections (UTI) are the most common serious bacterial infection in febrile infants. Urinalysis (UA) is a screening test for preliminary diagnosis of UTI. UA can be performed manually or using automated techniques. We sought to compare manual versus automated UA for urine specimens obtained via catheterization in the pediatric emergency department. Methods In this prospective study, we processed catheterized urine samples from infants with suspected UTI by both the manual method (enhanced UA) and the automated method. We defined a positive enhanced UA as ≥ 10 white blood cells per cubic millimeter and presence of any bacteria per 10 oil immersion fields on a Gram-stained smear. We defined a positive automated UA as ≥ 2 white blood cells per high-powered field and presence of any bacteria using the IRIS iQ200 ELITE. We defined a positive urine culture as growth of ≥ 50,000 colony-forming units per milliliter of a single uropathogen. We analyzed data using SPSS software. Results A total of 703 specimens were analyzed. Prevalence of UTI was 7%. For pyuria, the sensitivity and positive predictive value (PPV) of the enhanced UA in predicting positive urine culture were 83.6% and 52.5%, respectively; corresponding values for the automated UA were 79.5% and 37.5%, respectively. For bacteriuria, the sensitivity and PPV of a Gram-stained smear (enhanced UA) were 83.6% and 59.4%, respectively; corresponding values for the automated UA were 73.4%, and 26.2%, respectively. Using criteria of both pyuria and bacteriuria for the enhanced UA resulted in a sensitivity of 77.5% and a PPV of 84.4%; corresponding values for the automated UA were 63.2% and 51.6%, respectively. Combining automated pyuria (≥ 2 white blood cells/high-powered microscopic field) with a Gram-stained smear resulted in a sensitivity of 75.5% and a PPV of 84%. Conclusions Automated UA is comparable with manual UA for detection of pyuria in young children with suspected UTI. Bacteriuria detected by automated UA is less sensitive and specific for UTI when compared with a Gram-stained smear. We recommend using either manual or automated measurement of pyuria in combination with Gram-stained smear as the preferred technique for UA of catheterized specimens obtained from children in an acute care setting.

Objective To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. Study design A total of 206 children meeting a priori clinical criteria for acute sinusitis who were prescribed antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8-12 days after treatment was initiated was followed with the use of a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8-10 years after the 7-valent pneumococcal conjugate vaccination was introduced but before introduction of the 13-valent pneumococcal conjugate vaccination. Results Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs 8.5 median days to symptom resolution) than those who were not colonized with S pneumoniae . Age and radiograph findings did not predict time to symptom resolution. Conclusions In children with acute sinusitis, proven nasopharyngeal colonization with S pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment.

We present a light field digital otoscope designed to measure three-dimensional shape of the tympanic membrane. This paper describes the optical and anatomical considerations we used to develop the prototype, along with the simulation and experimental measurements of vignetting, field curvature, and lateral resolution. Using an experimental evaluation procedure, we have determined depth accuracy and depth precision of our system to be 0.05–0.07 mm and 0.21–0.44 mm, respectively. To demonstrate the application of our light field otoscope, we present the first three-dimensional reconstructions of tympanic membranes in normal and otitis media conditions, acquired from children who participated in a feasibility study at the Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center.

Objective To assess whether antimicrobial therapy in young children with acute otitis media reduces time to resolution of symptoms, overall symptom burden, and persistence of otoscopic evidence of infection. We used a cost-utility model to evaluate whether immediate antimicrobial treatment seems to be worthwhile, and if so, which antimicrobial agent is most cost effective. Study design We compared the cost per quality-adjusted life-day of 5 treatment regimens in children younger than 2 years of age with acute otitis media: immediate amoxicillin/clavulanate, immediate amoxicillin, immediate cefdinir, watchful waiting, and delayed prescription (DP) for antibiotic. Results The 5 treatment regimens, listed in order from least effective to most effective were DP, watchful waiting, immediate cefdinir, immediate amoxicillin, and immediate amoxicillin/clavulanate. Listed in order from least costly to most costly, the regimens were DP, immediate amoxicillin, watchful waiting, immediate amoxicillin/clavulanate, and immediate cefdinir. The incremental cost-utility ratio of immediate amoxicillin compared with DP was $101.07 per quality-adjusted life-day gained. The incremental cost-utility ratio of immediate amoxicillin/clavulanate compared with amoxicillin was $2331.28 per quality-adjusted life-day gained. Conclusions In children younger than 2 years of age with acute otitis media and no recent antibiotic exposure, immediate amoxicillin seems to be the most cost-effective initial treatment.

Importance Although prior studies have suggested that the risk of renal scarring gradually increases with each febrile urinary tract infection (UTI), recent and detailed data are lacking. Objective To evaluate how the risk of renal scarring is associated with the number of febrile UTIs. Design, Setting, and Participants A post hoc analysis was performed from June 2018 to April 2019 of data collected in the context of 2 multicenter prospective studies (RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux], conducted from June 2007 to June 2013, and CUTIE [Careful Urinary Tract Infection Evaluation], conducted from May 2008 to October 2013), of children with a first UTI without baseline renal abnormalities who were followed up for 2 years for febrile recurrences. Exposure Number of known febrile UTIs. Main Outcomes and Measures Renal scarring was defined as decreased uptake of tracer associated with the loss of contours or cortical thinning on a technetium 99m dimercaptosuccinic acid renal scan obtained at study exit or approximately 4 months after the last febrile UTI. Results A total of 345 children were included (307 girls and 38 boys; mean [SD] age, 19.4 [18.2] months; 221 with vesicoureteral reflux and 124 without vesicoureteral reflux). The incidence of renal scarring was 2.8% (95% CI, 1.2%-5.8%) after 1 febrile UTI, 25.7% (95% CI, 12.5%-43.3%) after 2 febrile UTIs, and 28.6% (95% CI, 8.4%-58.1%) after 3 or more febrile UTIs. The odds of renal scarring after a second febrile infection were 11.8 (95% CI, 4.1-34.4) times greater than after a single febrile infection, and the odds of renal scarring after 3 or more febrile infections were 13.7 (95% CI, 3.4-54.4) times greater than after a single febrile infection. Conclusions and Relevance Although relatively few children have 2 febrile UTIs, those who do have a substantially higher risk of renal scarring compared with children with a single febrile UTI. This finding suggests that research should focus on the identification of biomarkers that could noninvasively identify children at risk for subsequent febrile infections. More research is also needed to understand the molecular basis of the increased risk of renal scarring among children with recurrent febrile UTIs.

Objective To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. Study design We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. Results Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. Conclusions Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

OBJECTIVE: To develop a parent-reported pediatric rhinosinusitis symptom scale (PRSS) that could be used to monitor symptoms of young children with acute sinusitis in response to therapy STUDY DESIGN: We developed an 8-item symptom severity scale and evaluated its internal reliability, construct validity, and responsiveness in children 2 to 12 years of age with acute sinusitis. Parents of 258 children with acute sinusitis completed the PRSS at the time of diagnosis, as a diary at home, and at the follow-up visit at day 10 to 12. Based on psychometric results and additional parent feedback, we revised the scale. We evaluated the revised version in 185 children with acute sinusitis. RESULTS: Correlations between the scale and reference measures on the day of enrollment were in the expected direction and of the expected magnitude. PRSS scores at the time of presentation correlated with radiographic findings (P < .001), functional status (p

Background ABS is one of the most common infections in childhood leading to antibiotic prescriptions, but remains a clinical diagnosis. Laboratory testing does not aid diagnosis and there are no predictors to identify those who will respond to therapy or develop complications. Thus, the tools to diagnose and manage ABS remain limited. Initial viral infection predisposes to development of ABS. However, there is poor understanding of the contribution of viral infection to pathogenesis, rate of complications, or the immune response to ABS. The objective of this study was to define bacterial upper airway colonization, viral co-infection and cytokine response in the upper airway during ABS. Methods In the context of an ongoing larger prospective clinical study, children were enrolled who were diagnosed with ABS using standardized clinical criteria. Nasopharyngeal (NP) samples were processed for bacterial culture for S. pneumoniae, H. influenzae, S. pyogenes and M. catarrhalis; real-time PCR viral testing and cytokine measurement by qPCR. We correlated these findings with clinical symptoms at the time of presentation. Results Of 184 enrolled children (median age 4.9 years), 134 (72.8%) had a positive bacterial culture for potentially pathogenic bacteria and 50 (27.2%) had growth of normal flora. A total of 129 (70.4%) subjects tested positive for a virus. The most common virus detected was rhinovirus (n = 86) followed by influenza virus (n = 23) and adenovirus (n = 21). A total of 102 patients (70.4%) had both a positive pathogenic bacterial culture and viral detection. Patients who had a bacterial pathogen plus a viral detection had a significantly higher expression of IL-6, IL-8 and IL-25 (P < 0.001). Univariable analysis found no correlation between clinical presentation with viral and/or cytokine expressions. Conclusion Children meeting clinical criteria for ABS and a NP swab with a pathogenic bacteria plus viral detection demonstrated higher expression of inflammatory cytokines compared with subjects whose culture had normal respiratory flora. Disclosures J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee.

The diagnosis of acute bacterial sinusitis can be challenging because symptoms of acute sinusitis and an upper respiratory tract infection (URI) overlap. A rapid test, if accurate in differentiating sinusitis from URI, could be helpful in the diagnostic process. We examined the utility of nasopharyngeal cultures in identifying the subgroup of children with a clinical diagnosis of acute sinusitis who are least likely to benefit from antimicrobial therapy (those with completely normal sinus radiographs). Nasopharyngeal swabs were collected from 204 children meeting a priori clinical criteria for acute sinusitis. All children had sinus X-rays at the time of diagnosis. To determine if negative nasopharyngeal culture results could reliably identify the subgroup of children with normal radiographs, we calculated negative predictive values and negative likelihood ratios. Absence of pathogens in the nasopharynx was not helpful in identifying this low-risk subgroup.