Urinary Tract Infections in Children.

Despite the American Academy of Pediatrics guidelines for the evaluation, treatment, and management of urinary tract infections (UTIs), UTI diagnosis and management remains challenging for clinicians. Challenges with acute UTI management stem from vague presenting signs and symptoms, diagnostic uncertainty, limitations in laboratory testing, and selecting appropriate antibiotic therapy in an era with increasing rates of antibiotic-resistant uropathogens. Recurrent UTI management remains difficult due to an incomplete understanding of the factors contributing to UTI, when to assess a child with repeated infections for kidney and urinary tract anomalies, and limited prevention strategies. To help reduce these uncertainties, this review provides a comprehensive overview of UTI epidemiology, risk factors, diagnosis, treatment, and prevention strategies that may help pediatricians overcome the challenges associated with acute and recurrent UTI management.

Preterm and Term Infants Evaluated for Sepsis: Differences in Management and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: To describe differences in practice patterns and outcomes of young preterm versus age-matched term infants evaluated for sepsis, because evaluation and management of this group are not well defined. METHODS: We conducted a retrospective single-center study at an academic, freestanding children's hospital of previously healthy preterm and term infants aged 0 to 60 days, who presented for initial evaluation of fever and/or hypothermia from 2014 to 2019. We classified infants by gestational age as preterm (32-36 6/7 weeks) and term (37-42 weeks) and compared diagnostic evaluation, management, and clinical outcomes. RESULTS: Out of 363 preterm infants evaluated for sepsis, 336 met inclusion criteria; within the same study period, 2331 term infants were evaluated for sepsis, of which 600 were randomly selected and 554 were included. Clinicians performed inflammatory marker testing and chest x-rays more frequently in preterm infants 31% vs 25% (P = .034) and 50% vs 32% (P < .001), respectively. Preterm infants had a higher rate of bacteremia 5.9% vs 2.5% (P = .035), were hospitalized more frequently 72% vs 63% (P = .006), and required ICU level of care more often 32% vs 5% (P < .001) than term infants. They had lower rates of viral infections 33% vs 42% (P = .015) and no significant increased return visits. Febrile preterm and term infants, and older hypothermic preterm infants had relatively higher rates of serious bacterial infections. Hypothermic preterm infants had the longest hospitalizations. CONCLUSIONS: Preterm infants had increased rates of bacteremia and required higher level of care compared with age-matched term infants, likely reflecting their increased risk for sepsis and other concomitant morbidities associated with preterm birth.

Implementation and Patient Outcomes of a Pediatric COVID-19 Monoclonal Antibody Program.

BACKGROUND: The severity and reach of the COVID-19 pandemic drove the development of various therapeutic approaches to combat SARS-CoV-2, including several neutralizing monoclonal antibody (mAb) therapies. A January 2021 pediatric consensus statement opposed routine use and recommended individualized risk assessments when considering COVID-19 mAb therapies in children and adolescents due to limited data. This report describes the implementation of a mAb referral process and the clinical outcomes of patients who received a mAb infusion in a pediatric hospital. METHODS: We developed a tiered allocation system based on underlying medical conditions and incorporated it into a standardized COVID-19 mAb referral and approval process. Demographics and clinical data were collected on all patients who received mAb therapy for treatment or post-exposure prophylaxis. Data recorded included sociodemographics, qualifying underlying medical conditions, clinical manifestations of infection, and overall course of treatment and disease. RESULTS: A total of 182 patients ≤21 years old received a COVID-19 mAb infusion between November 27, 2020 and January 26, 2022. Patient age ranged from 10 months to 21 years, with a median age of 15 years. In total, 7 patients (4%) had suspected adverse reactions during the infusion, and 15 (8%) patients required a COVID-19-related visit within 30 days of the mAb infusion. CONCLUSIONS: A tiered allocation process may provide the framework for the stratification and efficient distribution of mAb therapies. Future research must focus on the efficacy of these therapies in the pediatric population, standardized therapeutic prioritization, and the optimal timeframe for mAb delivery to prevent progression to severe disease.

Novel urine biomarkers to distinguish UTI from culture-negative pyuria.

BACKGROUND: Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. METHODS: In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. RESULTS: BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). CONCLUSIONS: BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI.

Increasing Adherence to Acute Otitis Media Treatment Duration Guidelines using a Quality Improvement Approach.

This quality improvement initiative aimed to improve American Academy of Pediatrics acute otitis media (AOM) guideline adherence in pediatric urgent care sites by increasing the percentage of patients 2 years and older with AOM who received a short duration (7 days or fewer) of antibiotics from a baseline of 7% to a goal of 50%. METHODS: This quality improvement initiative was conducted in a network of seven urgent care sites affiliated with a large academic children's hospital. The interventions focused on clinician and family education, clinical decision support, and a discharge template that defaulted to a 7-day duration of antibiotics for patients 2 years and older diagnosed with AOM. The outcome measure was the percentage of patients receiving 7 days or fewer of antibiotics. The process measure was the percentage of prescriptions originating from the new discharge template. A repeat visit for AOM within 30 days from the initial visit was the balancing measure. RESULTS: The percentage of patients diagnosed with AOM receiving a short antibiotic course increased from a baseline of 7% to a new centerline mean of 67%, which exceeded the goal. This project resulted in 10,138 antibiotic days being avoided. Eighty-two percent of short-course prescriptions originated from the discharge template. Repeat visits for AOM within 1 month of the initial visit did not increase. CONCLUSIONS: A quality improvement initiative combining education and clinical decision support improved adherence to AOM treatment duration guidelines and avoided unnecessary antibiotic exposure in a pediatric urgent care network without increasing treatment failures.

Empiric Vancomycin Reduction in a Pediatric Intensive Care Unit.

BACKGROUND: At our institution, empirical vancomycin is overused in children with suspected bacterial community-acquired infections (CAIs) admitted to the PICU because of high community rates of methicillin-resistant Staphylococcus aureus (MRSA). Our goal was to reduce unnecessary vancomycin use for CAIs in the PICU. METHODS: Empirical PICU vancomycin indications for suspected CAIs were developed by using epidemiological risk factors for MRSA. We aimed to reduce empirical PICU vancomycin use in CAIs by 30%. After retrospectively testing, the indications were implemented and monthly PICU empirical vancomycin use during baseline (May 2017-April 2018) and postintervention (May 2018-July 2019) periods. Education was provided to PICU providers, vancomycin indications were posted, and the antibiotic order set was revised. Statistical process control methods tracked improvement over time. Proven S aureus infections for which vancomycin was not empirically prescribed and linezolid or clindamycin use were balancing measures. RESULTS: We identified 1620 PICU patients with suspected bacterial CAIs. Empirical vancomycin decreased from a baseline of 73% to 45%, a 38% relative reduction. No patient not prescribed empirical vancomycin later required the addition of vancomycin or other MRSA-targeted antibiotics. There was no change in nephrotoxicity or in the balancing measures. CONCLUSIONS: Development of clear and concise recommendations, combined with clinician education and decision support via an order set, was an effective and safe strategy to reduce PICU vancomycin use. Retrospective validation of the recommendations with local data were key to obtaining PICU clinician buy in.

Implementation of a Pharmacist-Led Antimicrobial Time-Out for Medical-Surgery Services in an Academic Pediatric Hospital.

OBJECTIVE: This report describes a quality improvement initiative to implement a pharmacist-led antimicrobial time-out (ATO) in a large, freestanding pediatric hospital. Our goal was to reach 90% ATO completion and documentation for eligible patients hospitalized on general pediatric medicine or surgery services. METHODS: A multidisciplinary quality improvement team developed an ATO process and electronic documentation tool. Clinical pharmacists were responsible to initiate and document an ATO for pediatric medicine or surgery patients on or before the fifth calendar day of therapy. The quality improvement team educated pharmacists and physicians and provided ATO audit and feedback to the pharmacists. We used statistical process control methods to track monthly rates of ATO completion retrospectively from October 2017 through March 2018 and prospectively from April 2018 through April 2019. Additionally, we retrospectively evaluated the completion of 6 data elements in the ATO note over the final 12-month period of the study. RESULTS: Among 647 eligible antimicrobial courses over the 19-month study period, the mean monthly documentation rate increased from 54.6% to 83.5% (p < 0.001). The mean ATO documentation rate increased from 32.8% to 74.2% (p < 0.001) for the pediatric medicine service and from 65.0% to 88.1% for the pediatric surgery service (p = 0.006). Among 302 notes assessed for completeness, 35.8% had all the required data fields completed. A tentative antimicrobial stop date was the data element completed least often (49.3%). CONCLUSIONS: We implemented a pharmacist-led ATO, highlighting the role pharmacists play in antimicrobial stewardship. Additional efforts are needed to further increase ATO completion rates and to define treatment duration.

Surrogate testing of oral third-generation cephalosporin susceptibility to common uropathogens.

Cefazolin susceptibility of urine isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis predicts susceptibility to oral cephalosporins, but cefazolin-resistant isolates may be susceptible to oral third-generation cephalosporins. Among 194 urine isolates, we found >95% categorical agreement among oral third-generation cephalosporins. Surrogate testing of cefpodoxime for cefdinir, and vice versa, resulted in no major or very major errors, while combinations involving cefixime produced rare major and very major errors.

Relationship Between Clinical Factors and Duration of IV Antibiotic Treatment in Neonatal UTI.

OBJECTIVES: To describe practice patterns of intravenous (IV) antibiotic treatment duration in term neonates ≤28 days old with a urinary tract infection (UTI). METHODS: We performed a retrospective chart review of term neonates ≤28 days old hospitalized for UTI at 2 academic pediatric hospitals from 2012 to 2018. Neonates who were admitted to the PICU or with known preexisting renal and/or urologic anomalies or concomitant bacteremia were excluded. We examined clinical features, complications, and duration of IV antibiotic therapy. Univariate and multivariate analyses of long duration of IV antibiotics (>48 hours) were performed by using logistic regression. RESULTS: Of 310 neonates identified by diagnostic codes and chart review, 112 met criteria for inclusion. The median IV antibiotic duration was 49 hours (51% received IV antibiotics for >48 hours), and the median total antibiotic duration was 10 days. No demographic features or laboratory values correlated with IV antibiotic duration apart from age <7 days. The odds of long IV antibiotic duration increased if the neonate had a secondary diagnosis extending hospitalization (adjusted odds ratio [aOR] = 3.2; P = .002; 95% confidence interval [CI], 1.2-8.7), subspecialty consult (aOR = 4.79; P < .001; 95% CI, 1.87-12.3), or an abnormal renal ultrasound (aOR = 2.26; P = .02; 95% CI, 1.01-5.08). Only 1 neonate experienced treatment failure. CONCLUSIONS: Our study revealed the recent trend toward shorter IV antibiotic courses for healthy term neonates with UTI is inclusive of infants ≤28 days at these 2 sites. Few factors associated with neonates' initial clinical presentation appear to influence the length of IV antibiotic treatment.

Manifestations of Toxic Shock Syndrome in Children, Columbus, Ohio, USA, 2010-20171.

Data are limited on the incidence and management of streptococcal toxic shock syndrome (TSS) and nonstreptococcal TSS in children. We aimed to define the clinical patterns of TSS at Nationwide Children's Hospital in Ohio as they relate to published criteria, diagnostic decisions, and treatment options. Through retrospective chart reviews, we identified 58 patients with TSS (27 streptococcal, 31 nonstreptococcal) during January 2010-September 2017. We observed clinical and laboratory findings that are not part of TSS criteria, such as pyuria in streptococcal TSS (50% of patients) and pulmonary involvement (85%) and coagulopathy (92%) in nonstreptococcal TSS patients. Recommended treatment with clindamycin and intravenous immunoglobulin was delayed in streptococcal TSS patients without rash (3.37 days vs. 0.87 days in patients with rash), leading to prolonged hospitalization and complications. Incorporation of additional TSS signs and symptoms would be helpful in TSS diagnosis and management.

Clinical and Radiologic Manifestations of Bone Infection in Children with Cat Scratch Disease.

We identified 13 patients with cat scratch (Bartonella henselae) bone infection among those admitted to a large tertiary care children's hospital over a 12-year period. The median age was 7 years and the median time from onset of illness to diagnosis was 10 days. Multifocal osteomyelitis involving spine and pelvis was common; no patient had a lytic bone lesion. Median treatment duration was 28 days (IQR, 24.5 days). Despite significant variations in treatment duration and antimicrobial therapy choices, all patients showed improvement.

Outpatient antimicrobial stewardship targets for treatment of skin and soft-tissue infections.

OBJECTIVE: We sought to identify factors associated with long duration and/or non-first-line choice of treatment for pediatric skin and soft-tissue infections (SSTIs). DESIGN: Retrospective cohort study. SETTING: Ambulatory encounter claims of Medicaid-insured children lacking chronic medical conditions treated for SSTI and/or animal bite injury in Ohio in 2014. METHODS: For all diagnoses, long treatment duration was defined as treatment >7 days. Non-first-line choice of treatment for SSTI included treatment with 2 antimicrobials dispensed on the same calendar day or any treatment not listed in the Infectious Diseases Society of America guidelines. The adjusted odds of (1) long treatment duration and (2) non-first-line choice of treatment were calculated for patient age, prescriber type, and patient county of residence characteristics (ie, rural vs metropolitan area and poverty rate). RESULTS: Of 10,310 encounters with complete data available, long treatment duration was prescribed in 7,968 (77.3%). The most common duration of treatment prescribed was 10 days. A non-first-line choice was prescribed in 1,030 encounters (10%). Dispensation of 2 antimicrobials on the same calendar day was the most common reason for the non-first-line choice, and of these, trimethoprim-sulfamethoxazole plus a first-generation cephalosporin was the most common regimen. Compared to pediatricians, the adjusted odds ratio of long treatment duration was significantly lower for all other primary care specialties. Conversely, nonpediatricians were more likely to prescribe a non-first-line treatment choice. Patient residence in a high-poverty county increased the odds of both long duration and non-first-line choice of treatment. CONCLUSIONS: Healthcare claims may be utilized to measure opportunities for first-line choice and/or shorter duration of treatment for SSTI.

Urinary Tract Infection and Antimicrobial Stewardship in the Emergency Department.

OBJECTIVES: The aims of this study were to assess empiric antibiotic use for presumed urinary tract infection (UTI) in the emergency department (ED) and to determine how often urine culture results subsequently do not confirm the diagnosis. METHODS: This study is a retrospective cohort study of patients aged 21 years or younger in the Nationwide Children's Hospital ED from May 1, 2012, to October 31, 2012, who had a urinalysis and urine culture performed and were discharged home with empiric antibiotic therapy for presumed UTI. Patients with known urinary tract anomaly or antibiotic use in the previous 7 days were excluded. Confirmed UTI was defined as pyuria (>5 white blood cells per high-power field or dipstick positive for leukocyte esterase) and a positive urine culture (≥50,000 colony-forming units/mL of a uropathogen). RESULTS: Of the 175 enrolled patients, urine was obtained by clean catch in 138 (79%), catheterization in 35 (20%), first-pass void in 1 (0.6%), and undocumented method in 1 (0.6%). Pyuria was demonstrated in 164 patients (94%), but only 97 (55%) had a positive urine culture. The combination of pyuria and a positive urine culture confirmed UTI in 90 patients (51%). The most commonly prescribed antibiotics were cefdinir in 103 patients (59%), trimethoprim/sulfamethoxazole in 40 (23%), and ciprofloxacin in 23 (13%). The median duration of prescribed therapy was 10 days (interquartile range, 7-10 days). Treatment duration was correlated negatively with age (r = -0.53, P < 0.01). CONCLUSIONS: The current management of suspected UTI in ED patients results in unnecessary antibiotic exposure, highlighting an important opportunity for outpatient antimicrobial stewardship efforts.

Urine Culture Follow-up and Antimicrobial Stewardship in a Pediatric Urgent Care Network.

BACKGROUND AND OBJECTIVES: Empiric antibiotic therapy for presumed urinary tract infection (UTI) leads to unnecessary antibiotic exposure in many children whose urine culture results fail to confirm the diagnosis. The objective of this quality improvement study was to improve follow-up management of negative urine culture results in the off-campus urgent care network of Nationwide Children's Hospital to reduce inappropriate antibiotic exposure in children. METHODS: A multidisciplinary task force developed and implemented a protocol for routine nurse and clinician follow-up of urine culture results, discontinuation of unnecessary antibiotics, and documentation in the electronic medical record. Monthly antibiotic discontinuation rates were tracked in empirically treated patients with negative urine culture results from July 2013 through December 2015. Statistical process control methods were used to track improvement over time. Fourteen-day return visits for UTIs were monitored as a balancing measure. RESULTS: During the study period, 910 patients received empiric antibiotic therapy for UTIs but had a negative urine culture result. The antibiotic discontinuation rate increased from 4% to 84%, avoiding 3429 (40%) of 8648 antibiotic days prescribed. Among patients with discontinued antibiotics, none was diagnosed with a UTI within 14 days of the initial urgent care encounter. CONCLUSIONS: Implementation of a standard protocol for urine culture follow-up and discontinuation of unnecessary antibiotics was both effective and safe in a high-volume pediatric urgent care network. Urine culture follow-up management is an essential opportunity for improved antimicrobial stewardship in the outpatient setting that will affect many patients by avoiding a substantial number of antibiotic days.

Healthcare Claims Data: An Underutilized Tool for Pediatric Outpatient Antimicrobial Stewardship.

BACKGROUND.: Healthcare claims are underutilized to identify factors associated with high outpatient antibiotic use. METHODS.: We evaluated ambulatory encounter claims of Medicaid-insured children in 34 Ohio counties in 2014. Rates of total antibiotic and azithromycin prescriptions dispensed were determined by county of patient residence. Standardized treatment rates by county were estimated for uncomplicated upper respiratory tract encounters (acute otitis media, pharyngitis, sinusitis, presumed viral infection) after adjusting for patient age and encounter provider type. Uncomplicated encounters included healthy children at initial presentation of illness. Adjusted odds of treatment were calculated for patient age, provider type, and county characteristics (rural vs metropolitan; poverty rate). RESULTS.: Retail pharmacies dispensed 255291 antibiotics to this cohort in 2014. More than 25% were to children <3 years. County rates of total antibiotic and azithromycin prescriptions dispensed were 530.4-1548.3 and 57.3-378.7 per 1000 person-years, respectively. Of 246866 uncomplicated upper respiratory tract encounters, antibiotics were dispensed (within 3 days) in 46.1%. Presumed viral infection accounted for 18.5% of antibiotics. Standardized treatment rates by county ranged widely from 35.9% (95% confidence interval [CI], 33.3%-38.5%) to 63.2% (95% CI, 61.5%-64.9%). Compared to encounters with pediatricians, adjusted odds ratio of treatment was 2.02 (95% CI, 1.96-2.07) for family physicians and 1.74 (95% CI, 1.68-1.79) for nurse practitioners. Residence in rural or high-poverty counties increased odds of treatment. CONCLUSIONS.: Healthcare claims were useful to identify populations and providers with high antibiotic use. Claims data could be considered to track and report antibiotic prescribing frequency, especially where electronic medical records are not available.

Thoracic osteomyelitis and epidural abscess formation due to cat scratch disease: case report.

Osteomyelitis of the spine with associated spinal epidural abscess represents an uncommon entity in the pediatric population, requiring prompt evaluation and diagnosis to prevent neurological compromise. Cat scratch disease, caused by the pathogen Bartonella henselae, encompasses a wide spectrum of clinical presentations; however, an association with osteomyelitis and epidural abscess has been reported in only 4 other instances in the literature. The authors report a rare case of multifocal thoracic osteomyelitis with an epidural abscess in a patient with a biopsy-proven pathogen of cat scratch disease. A 5-year-old girl, who initially presented with vague constitutional symptoms, was diagnosed with cat scratch disease following biopsy of an inguinal lymph node. Despite appropriate antibiotics, she presented several weeks later with recurrent symptoms and back pain. Magnetic resonance imaging revealed 2 foci of osteomyelitis at T-8 and T-11 with an associated anterior epidural abscess from T-9 to T-12. Percutaneous image-guided vertebral biopsy revealed B. henselae by polymerase chain reaction analysis, and she was treated conservatively with doxycycline and rifampin with favorable clinical outcome.

Evaluation of novel urinary tract infection biomarkers in children.

BACKGROUND: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children. METHODS: We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1-3, and test combinations were compared. RESULTS: For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82-0.93), respectively. Compared to LE ≥ trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone. CONCLUSION: Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children.