Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial.

Importance: The large overlap between symptoms of acute sinusitis and viral upper respiratory tract infection suggests that certain subgroups of children being diagnosed with acute sinusitis, and subsequently treated with antibiotics, derive little benefit from antibiotic use. Objective: To assess if antibiotic therapy could be appropriately withheld in prespecified subgroups. Design, Setting, and Participants: Randomized clinical trial including 515 children aged 2 to 11 years diagnosed with acute sinusitis based on clinical criteria. The trial was conducted between February 2016 and April 2022 at primary care offices affiliated with 6 US institutions and was designed to evaluate whether symptom burden differed in subgroups defined by nasopharyngeal Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis on bacterial culture and by the presence of colored nasal discharge. Interventions: Oral amoxicillin (90 mg/kg/d) and clavulanate (6.4 mg/kg/d) (n = 254) or placebo (n = 256) for 10 days. Main Outcomes and Measures: The primary outcome was symptom burden based on daily symptom scores on a validated scale (range, 0-40) during the 10 days after diagnosis. Secondary outcomes included treatment failure, adverse events including clinically significant diarrhea, and resource use by families. Results: Most of the 510 included children were aged 2 to 5 years (64%), male (54%), White (52%), and not Hispanic (89%). The mean symptom scores were significantly lower in children in the amoxicillin and clavulanate group (9.04 [95% CI, 8.71 to 9.37]) compared with those in the placebo group (10.60 [95% CI, 10.27 to 10.93]) (between-group difference, -1.69 [95% CI, -2.07 to -1.31]). The length of time to symptom resolution was significantly lower for children in the antibiotic group (7.0 days) than in the placebo group (9.0 days) (P = .003). Children without nasopharyngeal pathogens detected did not benefit from antibiotic treatment as much as those with pathogens detected; the between-group difference in mean symptom scores was -0.88 (95% CI, -1.63 to -0.12) in those without pathogens detected compared with -1.95 (95% CI, -2.40 to -1.51) in those with pathogens detected. Efficacy did not differ significantly according to whether colored nasal discharge was present (the between-group difference was -1.62 [95% CI, -2.09 to -1.16] for colored nasal discharge vs -1.70 [95% CI, -2.38 to -1.03] for clear nasal discharge; P = .52 for the interaction between treatment group and the presence of colored nasal discharge). Conclusions: In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens on presentation, and its effects did not depend on the color of nasal discharge. Testing for specific bacteria on presentation may represent a strategy to reduce antibiotic use in this condition. Trial Registration: ClinicalTrials.gov Identifier: NCT02554383.

Constipation on abdominal radiograph as potential risk factor for recurrent urinary tract infection development.

BACKGROUND: To compare clinical history and measurements of fecal load on abdominal radiography (AR) in the prediction of urinary tract infection (UTI) recurrence in children. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media.

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 ß-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.).

Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial.

Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI). Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI. Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials. Intervention: Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy). Main Outcome Measures: The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms. Results: Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms. Conclusions and Relevance: In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01595529.

The role of renal contour change in the diagnosis of cortical scarring after urinary tract infection.

Urinary tract infections in children can lead to permanent renal scarring in approximately 15% of cases. Technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) scintigraphy is the gold standard for identifying renal scarring. Using data and scans from children enrolled at our center in a 2-year prospective clinical trial (RIVUR study), we included children with radiologically confirmed pyelonephritis who exhibited renal scarring on their 1 and/or 2-year follow-up scans and asked 3 blinded pediatric nuclear medicine physicians to reexamine the renal contours in these scans. Five girls met all eligibility criteria (each had two late 99mTc-DMSA scans 1 and 2 years after index UTI). Of the 20 kidneys imaged, 10 exhibited renal scarring and of these, 7 exhibited renal contour abnormalities. These findings suggest that the presence of abnormalities of the renal contour is not necessary for diagnosis of renal scarring.

Intranasal Surfactant for Acute Otitis Media: A Randomized Trial.

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.

Comparison of Bacterial Culture Results Obtained from Nasopharyngeal and Midturbinate Swabs in Children With Upper Respiratory Tract Infection Symptoms.

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.

Successful Management of Chylothorax With Etilefrine: Case Report in 2 Pediatric Patients.

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.

Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children.

Importance: Accurately estimating the probability of urinary tract infection (UTI) in febrile preverbal children is necessary to appropriately target testing and treatment. Objective: To develop and test a calculator (UTICalc) that can first estimate the probability of UTI based on clinical variables and then update that probability based on laboratory results. Design, Setting, and Participants: Review of electronic medical records of febrile children aged 2 to 23 months who were brought to the emergency department of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. An independent training database comprising 1686 patients brought to the emergency department between January 1, 2007, and April 30, 2013, and a validation database of 384 patients were created. Five multivariable logistic regression models for predicting risk of UTI were trained and tested. The clinical model included only clinical variables; the remaining models incorporated laboratory results. Data analysis was performed between June 18, 2013, and January 12, 2018. Exposures: Documented temperature of 38°C or higher in children aged 2 months to less than 2 years. Main Outcomes and Measures: With the use of culture-confirmed UTI as the main outcome, cutoffs for high and low UTI risk were identified for each model. The resultant models were incorporated into a calculation tool, UTICalc, which was used to evaluate medical records. Results: A total of 2070 children were included in the study. The training database comprised 1686 children, of whom 1216 (72.1%) were female and 1167 (69.2%) white. The validation database comprised 384 children, of whom 291 (75.8%) were female and 200 (52.1%) white. Compared with the American Academy of Pediatrics algorithm, the clinical model in UTICalc reduced testing by 8.1% (95% CI, 4.2%-12.0%) and decreased the number of UTIs that were missed from 3 cases to none. Compared with empirically treating all children with a leukocyte esterase test result of 1+ or higher, the dipstick model in UTICalc would have reduced the number of treatment delays by 10.6% (95% CI, 0.9%-20.4%). Conclusions and Relevance: UTICalc estimates the probability of UTI by evaluating the risk factors present in the individual child. As a result, testing and treatment can be tailored, thereby improving outcomes for children with UTI.