Antibiotics for Acute Sinusitis in Children: A Meta-Analysis.

CONTEXT: Acute sinusitis is one of the leading causes of antibiotic prescriptions in children. No recent systematic reviews have examined the efficacy of antibiotics compared with placebo. OBJECTIVE: We sought to determine if antibiotics are superior to placebo in the treatment of acute sinusitis in children. DATA SOURCES: Medline and Embase were searched from their origin to July 2023. STUDY SELECTION: We considered randomized placebo-controlled studies focusing on the treatment of acute sinusitis. In all studies, symptoms were present for <4 weeks and subjects were <18 years of age. DATA EXTRACTION: Two authors independently extracted the data. We pooled data primarily using fixed-effects models. RESULTS: Analysis of 6 included studies showed that antibiotic treatment reduced the rate of treatment failure by 41% (with a risk ratio of 0.59; 95% confidence interval 0.49-0.72) compared with placebo. There was substantial heterogeneity between the studies (I2 = 69.7%), which decreased substantially when the 1 study with a high risk of bias was removed (I2 = 26.9%). Children treated with antibiotics were 1.6 times more likely to have diarrhea than those who were not treated with antibiotics (risk ratio = 1.62, 95% confidence interval 1.04-2.51). LIMITATIONS: A small number of studies were eligible for inclusion. Included studies differed in their methodology. CONCLUSIONS: In children with clinically diagnosed acute sinusitis, antibiotics significantly reduced the rate of treatment failure compared with placebo. However, given the favorable natural history of sinusitis, our results could also support close observation without immediate antibiotic treatment.

Nasopharyngeal metatranscriptomics reveals host-pathogen signatures of pediatric sinusitis.

Acute sinusitis (AS) is the fifth leading cause of antibiotic prescriptions in children. Distinguishing bacterial AS from common viral upper respiratory infections in children is crucial to prevent unnecessary antibiotic use but is challenging with current diagnostic methods. Despite its speed and cost, untargeted RNA sequencing of clinical samples from children with suspected AS has the potential to overcome several limitations of other methods. However, the utility of sequencing-based approaches in analysis of AS has not been fully explored. Here, we performed RNA-seq of nasopharyngeal samples from 221 children with clinically diagnosed AS to characterize their pathogen and host-response profiles. Results from RNA-seq were compared with those obtained using culture for three common bacterial pathogens and qRT-PCR for 12 respiratory viruses. Metatranscriptomic pathogen detection showed high concordance with culture or qRT-PCR, showing 87%/81% sensitivity (sens) / specificity (spec) for detecting bacteria, and 86%/92% (sens/spec) for viruses, respectively. We also detected an additional 22 pathogens not tested for in the clinical panel, and identified plausible pathogens in 11/19 (58%) of cases where no organism was detected by culture or qRT-PCR. We assembled genomes of 205 viruses across the samples including novel strains of coronaviruses, respiratory syncytial virus (RSV), and enterovirus D68. By analyzing host gene expression, we identified host-response signatures that distinguished bacterial and viral infections and correlated with pathogen abundance. Ultimately, our study demonstrates the potential of untargeted metatranscriptomics for in depth analysis of the etiology of AS, comprehensive host-response profiling, and using these together to work towards optimized patient care.

Development and Validation of an Automated Classifier to Diagnose Acute Otitis Media in Children.

Importance: Acute otitis media (AOM) is a frequently diagnosed illness in children, yet the accuracy of diagnosis has been consistently low. Multiple neural networks have been developed to recognize the presence of AOM with limited clinical application. Objective: To develop and internally validate an artificial intelligence decision-support tool to interpret videos of the tympanic membrane and enhance accuracy in the diagnosis of AOM. Design, Setting, and Participants: This diagnostic study analyzed otoscopic videos of the tympanic membrane captured using a smartphone during outpatient clinic visits at 2 sites in Pennsylvania between 2018 and 2023. Eligible participants included children who presented for sick visits or wellness visits. Exposure: Otoscopic examination. Main Outcomes and Measures: Using the otoscopic videos that were annotated by validated otoscopists, a deep residual-recurrent neural network was trained to predict both features of the tympanic membrane and the diagnosis of AOM vs no AOM. The accuracy of this network was compared with a second network trained using a decision tree approach. A noise quality filter was also trained to prompt users that the video segment acquired may not be adequate for diagnostic purposes. Results: Using 1151 videos from 635 children (majority younger than 3 years of age), the deep residual-recurrent neural network had almost identical diagnostic accuracy as the decision tree network. The finalized deep residual-recurrent neural network algorithm classified tympanic membrane videos into AOM vs no AOM categories with a sensitivity of 93.8% (95% CI, 92.6%-95.0%) and specificity of 93.5% (95% CI, 92.8%-94.3%) and the decision tree model had a sensitivity of 93.7% (95% CI, 92.4%-94.9%) and specificity of 93.3% (92.5%-94.1%). Of the tympanic membrane features outputted, bulging of the TM most closely aligned with the predicted diagnosis; bulging was present in 230 of 230 cases (100%) in which the diagnosis was predicted to be AOM in the test set. Conclusions and Relevance: These findings suggest that given its high accuracy, the algorithm and medical-grade application that facilitates image acquisition and quality filtering could reasonably be used in primary care or acute care settings to aid with automated diagnosis of AOM and decisions regarding treatment.

Antimicrobial prophylaxis for vesicoureteral reflux: which subgroups of children benefit the most?

BACKGROUND: While the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that long-term antimicrobial prophylaxis reduced the risk of urinary tract infection (UTI) recurrences by 50%, 10 children had to be treated for one to benefit (i.e., observed number needed to treat (NNT) of 10). Accordingly, we re-analyzed RIVUR data to systematically identify subgroups of children with vesicoureteral reflux (VUR) with a smaller NNT. METHODS: Using patient-level data from the RIVUR trial, we applied penalized regression methods including the baseline age, VUR grade, type of index UTI, and bowel-bladder dysfunction (BBD) as covariates to identify subgroups. RESULTS: We identified four relevant subgroups of children that appear to benefit from long-term antimicrobial prophylaxis, all with observed NNTs smaller than or equal to 5: children with grade IV VUR, BBD, and febrile index UTI (1% of the sample), children with BBD and febrile index UTI (7% of the sample), children with BBD (12% of the sample), and children with grade IV VUR (8% of the sample). CONCLUSIONS: Use of long-term antimicrobial prophylaxis appears to be particularly relevant for children with BBD (and any grade of VUR) and those with grade IV VUR (regardless of BBD status). However, because details regarding the treatment of BBD are not available, further studies are needed to fully determine the role of prophylactic antimicrobials in the management of children with VUR who have BBD.

ISOM 2023 Research Panel 5: Interventions- Vaccines and prevention, medical and surgical treatment, and impact of COVID-19 pandemic.

OBJECTIVES: To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical treatment of uncomplicated otitis media (OM) including the impact of the COVID-19 pandemic on OM management. DATA SOURCES: Medline (PubMed), Embase, and the Cochrane Library. REVIEW METHODS: All relevant original articles published in English between June 2019 and February 2023 were identified. Studies related to guideline adherence, impact of treatment on immune response and/or microbiology, tympanoplasty, Eustachian tube balloon dilatation, mastoidectomy procedures, and those focusing on children with Down's syndrome or cleft palate were excluded. MAIN FINDINGS: Of the 9280 unique records screened, 64 were eligible for inclusion; 23 studies related to medical treatment, 20 to vaccines, 13 to surgical treatment, 6 to prevention (excl. vaccines) and 2 to the impact of COVID-19 on OM management. The level of evidence was judged 2 in 11 studies (17.2 %) and 3 or 4 in the remaining 53 studies (82.8 %) mainly due to the observational design, study limitations or low sample sizes. Some important advances in OM management have been made in recent years. Video discharge instructions detailing the identification and management of pain and fever for parents of children with acute otitis media (AOM) was more effective than paper instructions in reducing symptomatology; compared to placebo, levofloxacin solution was more effective for treating chronic suppurative otitis media, whereas AOM recurrences during two years of follow-up did not differ between children with recurrent AOM who received tympanostomy tube (TT) insertion or medical management. Further, novel pneumococcal conjugate vaccines (PCV) schedules for preventing OM in Aboriginal children appeared ineffective, and a protein-based pneumococcal vaccine had no added value over PCV13 for preventing AOM in native American infants. During the COVID-19 pandemic, a decline in OM and TT case volumes and complications was observed. IMPLICATION FOR PRACTICE AND FUTURE RESEARCH: Whether the observed impact of the COVID-19 pandemic on OM management extends to the post-pandemic era is uncertain. Furthermore, the impact of the pandemic on the conduct of urgently needed prospective methodologically rigorous interventional studies aimed at improving OM prevention and treatment remains to be elucidated since the current report consisted of studies predominantly conducted in the pre-pandemic era.

Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis.

BACKGROUND: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. AIM: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023376769.

Measuring and Reducing Racial Bias in a Pediatric Urinary Tract Infection Model.

Clinical predictive models that include race as a predictor have the potential to exacerbate disparities in healthcare. Such models can be respecified to exclude race or optimized to reduce racial bias. We investigated the impact of such respecifications in a predictive model - UTICalc - which was designed to reduce catheterizations in young children with suspected urinary tract infections. To reduce racial bias, race was removed from the UTICalc logistic regression model and replaced with two new features. We compared the two versions of UTICalc using fairness and predictive performance metrics to understand the effects on racial bias. In addition, we derived three new models for UTICalc to specifically improve racial fairness. Our results show that, as predicted by previously described impossibility results, fairness cannot be simultaneously improved on all fairness metrics, and model respecification may improve racial fairness but decrease overall predictive performance.

Support for the Use of a New Cutoff to Define a Positive Urine Culture in Young Children.

BACKGROUND: Conventional urine culture selects for a narrow range of organisms that grow well in aerobic conditions. In contrast, examination of bacterial gene sequences in the urine provides a relatively unbiased evaluation of the organisms present. Thus, by using 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing as the reference standard, we now have the ability to assess the accuracy of urine culture in diagnosing urinary tract infection (UTI). METHODS: We enrolled febrile children 1 month to 3 years of age that underwent bladder catheterization for suspected UTI. Using 16S rRNA gene amplicon sequencing as the reference standard, we calculated the accuracy of urine culture at various cutoffs (10 000, 50 000, and 100 000 colony forming units per milliliter). Children with ≥80% relative abundance of any organism on 16S rRNA gene amplicon sequencing with elevated urinary markers of inflammation were defined as having a UTI. RESULTS: When using a cutoff of 10 000 CFU/mL, the sensitivity and specificity of urine culture were 98% (95% confidence interval [CI]: 93%-100%) and 99% (95% CI: 97%-100%), respectively. Using a cutoff of 50 000 colony forming units per mL decreased sensitivity to 80% (95% CI: 68%-93%) without changing the specificity. Using a cutoff of 100 000 further decreased sensitivity to 70% (95% CI: 55%-84%). CONCLUSIONS: Conventional culture remains an accurate method of diagnosing UTIs in young children; however, these data suggest that a cutoff of 10 000 colony forming units per mL provides the optimal balance between sensitivity and specificity for children undergoing bladder catheterization.

Antimicrobial prophylaxis for vesicoureteral reflux: which subgroups of children benefit the most?

Background: While the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) trial found that long-term antimicrobial prophylaxis reduced the risk of urinary tract infection (UTI) recurrences by 50%, 10 children had to be treated with long-term antimicrobial prophylaxis for one to benefit (i.e., observed number needed to treat (NNT) of 10). Accordingly, we re-analyzed RIVUR data to systematically identify subgroups of children with vesicoureteral reflux (VUR) with a smaller NNT. Methods: Using patient-level data from the RIVUR trial, we applied penalized regression methods including the baseline age, VUR, and bowel-bladder dysfunction (BBD) as covariates to identify subgroups that consider the trade-off between absolute risk difference and size. Results: We identified three relevant subgroups of children that appear to benefit from long-term antimicrobial prophylaxis, all with NNTs smaller than the NNT of 10. Children with grade IV VUR and BBD, 1% of the RIVUR sample, had a NNT of 2; children with BBD, 12% of the RIVUR sample, had a NNT of 4; children with BBD (and any grade VUR) or with grade IV VUR (regardless of BBD status), which was the combination of the first two subgroups and included 19% of children in the RIVUR sample, had a NNT of 4. Conclusions: Use of long-term antimicrobial prophylaxis appears to be particularly relevant for children with BBD (and any grade of VUR) or those with grade IV VUR (regardless of BBD status) who were at high risk of UTI recurrences.

Genomic classification and antimicrobial resistance profiling of Streptococcus pneumoniae and Haemophilus influenza isolates associated with paediatric otitis media and upper respiratory infection.

Acute otitis media (AOM) is the most common childhood bacterial infectious disease requiring antimicrobial therapy. Most cases of AOM are caused by translocation of Streptococcus pneumoniae or Haemophilus influenzae from the nasopharynx to the middle ear during an upper respiratory tract infection (URI). Ongoing genomic surveillance of these pathogens is important for vaccine design and tracking of emerging variants, as well as for monitoring patterns of antibiotic resistance to inform treatment strategies and stewardship.In this work, we examined the ability of a genomics-based workflow to determine microbiological and clinically relevant information from cultured bacterial isolates obtained from patients with AOM or an URI. We performed whole genome sequencing (WGS) and analysis of 148 bacterial isolates cultured from the nasopharynx (N = 124, 94 AOM and 30 URI) and ear (N = 24, all AOM) of 101 children aged 6-35 months presenting with AOM or an URI. We then performed WGS-based sequence typing and antimicrobial resistance profiling of each strain and compared results to those obtained from traditional microbiological phenotyping.WGS of clinical isolates resulted in 71 S. pneumoniae genomes and 76 H. influenzae genomes. Multilocus sequencing typing (MSLT) identified 33 sequence types for S. pneumoniae and 19 predicted serotypes including the most frequent serotypes 35B and 3. Genome analysis predicted 30% of S. pneumoniae isolates to have complete or intermediate penicillin resistance. AMR predictions for S. pneumoniae isolates had strong agreement with clinical susceptibility testing results for beta-lactam and non beta-lactam antibiotics, with a mean sensitivity of 93% (86-100%) and a mean specificity of 98% (94-100%). MLST identified 29 H. influenzae sequence types. Genome analysis identified beta-lactamase genes in 30% of H. influenzae strains, which was 100% in agreement with clinical beta-lactamase testing. We also identified a divergent highly antibiotic-resistant strain of S. pneumoniae, and found its closest sequenced strains, also isolated from nasopharyngeal samples from over 15 years ago.Ultimately, our work provides the groundwork for clinical WGS-based workflows to aid in detection and analysis of H. influenzae and S. pneumoniae isolates.

Categorical Risk Stratification for Neonatal Early Onset Sepsis using Suspected Intraamniotic Infection and the Newborn Exam.

Objective: To determine test characteristics of categorical risk stratification for early onset sepsis (EOS) using maternal criteria for suspected intraamniotic infection (IAI) and/or newborn exam and compare them to the EOS calculator. Study Design: Retrospective 1:3 case-control study of late preterm/term infants with bacterial culture growth obtained <72 hours of life. For categorical approach, infants of mothers with suspected IAI or equivocal/ill appearing were presumed high-risk for EOS and blood culture obtained. For calculator, estimated probability of EOS and care recommendations were recorded from online calculator. Test characteristics were compared with McNemar's test; recommendation for blood culture was considered a "positive" test. Result: 52 cases and 172 controls were included. Compared to the calculator, the categorical approach had higher sensitivity 90%(95%CI:79-96%) vs 67% (95%CI:54-79%) but lower specificity 85%(95%CI:78-89%) vs. 92%(95%CI:87-96%). 10% of cases were not identified by either. Conclusion: A categorical approach using suspected IAI/newborn exam offers good EOS discrimination and is comparable to the calculator.

Genomic epidemiology and antibiotic susceptibility profiling of uropathogenic Escherichia coli among children in the United States.

Escherichia coli is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species is poorly understood within this age group. To investigate whether uropathogenic E. coli (UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full pap operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding papGII allele is substantially more prevalent in invasive UPEC from adults, we found papGII was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that fimH30, an allele of the fimbrial gene fimH often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the fimH30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by Escherichia coli, are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of E. coli sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children.

External Validation of the UTICalc with and Without Race for Pediatric Urinary Tract Infection.

OBJECTIVE: To validate externally the UTICalc, a popular clinical decision support tool used to determine the risk of urinary tract infections (UTIs) in febrile children, and compare its performance with and without the inclusion of race and at differing risk thresholds. METHODS: We performed a retrospective, singlecenter case-control study of febrile children (2-24 months) in an emergency department. Cases with culture-confirmed UTI were matched 1:1 to controls. We compared the performance of the original model which included race (version 1.0) to a revised model which did not consider race (version 3.0). We evaluated model performance at risk thresholds between 2% and 5%. RESULTS: We included 185 cases and 197 controls (median age 8.4 months; IQR, 4.4-13.0 months; 60.5% girls). When using UTICalc version 1.0, the model area under the receiver operator characteristic curve (AUROC) was 73.4% (95% CI 68.4%-78.5%), which was similar to the version 3.0 model (73.8%; 95% CI 68.7%-78.8%). When using a 2% risk threshold, the version 3.0 model demonstrated a sensitivity of 96.7% and a specificity of 25.0%, with declines in sensitivity and gains in specificity at higher risk thresholds. Version 1.0 of the UTICalc had 12 false negatives, of whom 10 were Black (83%); whereas version 3.0 had 6 false negatives, of whom 2 were Black (33%). CONCLUSIONS: Versions of the UTICalc with and without race had similar performance to each other with a slight decline from the original derivation sample. The removal of race did not adversely affect the accuracy of the UTICalc.

Moraxella Catarrhalis Infrequently Cultured from Middle Ear Fluid of Children with Acute Otitis Media.

We compared the distribution of organisms in the nasopharynx and the middle ear fluid in 164 episodes of acute otitis media in children 6-35 months of age. In contrast to Streptococcus pneumoniae and Haemophilus influenzae , Moraxella catarrhalis is isolated from the middle ear in only 11% of episodes with nasopharyngeal colonization with this organism.

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.

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.

Association Between Nasopharyngeal Colonization and Clinical Outcome in Children With Acute Otitis Media.

BACKGROUND: Young children with acute otitis media (AOM) frequently exhibit nasopharyngeal colonization with either Streptococcus pneumoniae, Haemophilus influenzae or both pathogens. We aimed to determine if antibiotics could be spared or shortened in those without nasopharyngeal colonization with either pathogen. METHODS: In 2 separate randomized clinical trials in children aged 6-23 months with stringently-diagnosed AOM, we performed bacterial cultures on nasopharyngeal specimens collected at the time of diagnosis. In the first trial, we compared the efficacy of amoxicillin/clavulanate (amox/clav) administered for 10 days vs. that of placebo, and in the second trial, we compared the efficacy of amox/clav administered for 10 days vs. 5 days. In each trial, we classified children as being colonized with both S. pneumoniae and H. influenzae, S. pneumoniae alone, H. influenzae alone, or neither pathogen, and as experiencing either clinical success or clinical failure at the end-of-therapy visit, based on previously reported a priori criteria. RESULTS: We evaluated 796 children. Among children randomized to amox/clav, those colonized with either S. pneumoniae or H. influenzae or both were approximately twice as likely to experience clinical failure as children not colonized with either pathogen (odds ratio: 1.8; confidence intervals: 1.2-2.9). In contrast, among children randomized to placebo, clinical failure at the end-of-therapy visit was not associated with nasopharyngeal culture results at the time of diagnosis. CONCLUSIONS: Children colonized with either S. pneumoniae or H. influenzae or both have a greater chance of treatment failure than children colonized with neither pathogen.

Biomarkers for febrile urinary tract infection in children.

Background: The current reference standard for pediatric urinary tract infection (UTI) screening, the leukocyte esterase (LE) dipstick test, has suboptimal accuracy. The objective of this study was to compare the accuracy of novel urinary biomarkers to that of the LE test. Methods: We prospectively enrolled febrile children who were evaluated for UTI based on their presenting symptoms. We compared the accuracy of urinary biomarkers to that of the test. Results: We included 374 children (50 with UTI, 324 without UTI, ages 1-35 months) and examined 35 urinary biomarkers. The urinary biomarkers that best discriminated between febrile children with and without UTI were urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-1ß, CXCL1, and IL-8. Of all examined urinary biomarkers, the urinary NGAL had the highest accuracy with a sensitivity of 90% (CI: 82-98) and a specificity of 96% (CI: 93-98). Conclusion: Because the sensitivity of the urinary NGAL test is slightly higher than that of the LE test, it can potentially reduce missed UTI cases. Limitations of using urinary NGAL over LE include increased cost and complexity. Further investigation is warranted to determine the cost-effectiveness of urinary NGAL as a screening test for UTI.