The COVID-19 Pandemic and Changes in Healthcare Utilization for Pediatric Respiratory and Nonrespiratory Illnesses in the United States.

The impact of COVID-19 public health interventions on pediatric illnesses nationwide is unknown. We performed a multicenter, cross-sectional study of encounters at 44 children's hospitals in the United States to assess changes in healthcare utilization during the pandemic. The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases; these large reductions were consistent across illness subgroups. Although encounters for nonrespiratory diseases decreased as well, reductions were more modest and varied by age. Encounters for respiratory diseases among adolescents declined to a lesser degree and returned to previous levels faster compared with those of younger children. Further study is needed to determine the contributions of decreased illness and changes in care-seeking behavior to this observed reduction.

Management and Outcomes in Children with Third-Generation Cephalosporin-Resistant Urinary Tract Infections.

BACKGROUND: Third-generation cephalosporin-resistant urinary tract infections (UTIs) often have limited oral antibiotic options with some children receiving prolonged parenteral courses. Our objectives were to determine predictors of long parenteral therapy and the association between parenteral therapy duration and UTI relapse in children with third-generation cephalosporin-resistant UTIs. METHODS: We conducted a multisite retrospective cohort study of children <18 years presenting to acute care at 5 children's hospitals and a large managed care organization from 2012 to 2017 with a third-generation cephalosporin-resistant UTI from Escherichia coli or Klebsiella spp. Long parenteral therapy was ≥3 days and short/no parenteral therapy was 0-2 days of concordant parenteral antibiotics. Discordant therapy was antibiotics to which the pathogen was non-susceptible. Relapse was a UTI from the same organism within 30 days. RESULTS: Of the 482 children included, 81% were female and the median age was 3.3 years (interquartile range: 0.8-8). Fifty-four children (11.2%) received long parenteral therapy (median duration: 7 days). Predictors of long parenteral therapy included age <2 months (adjusted odds ratio [aOR] 67.3; 95% confidence interval [CI]: 16.4-275.7), limited oral antibiotic options (aOR 5.9; 95% CI: 2.8-12.3), and genitourinary abnormalities (aOR 5.4; 95% CI: 1.8-15.9). UTI relapse occurred in 1 of the 54 (1.9%) children treated with long parenteral therapy and in 6 of the 428 (1.5%) children treated with short/no parenteral therapy (P = .57). Of the 105 children treated exclusively with discordant antibiotics, 3 (2.9%, 95% CI: 0.6%-8.1%) experienced UTI relapse. CONCLUSIONS: Long parenteral therapy was associated with age <2 months, limited oral antibiotic options, and genitourinary abnormalities. UTI relapse was rare and not associated with duration of parenteral therapy. For UTIs with limited oral options, further research is needed on the effectiveness of continued discordant therapy.

Clinical Response to Discordant Therapy in Third-Generation Cephalosporin-Resistant UTIs.

OBJECTIVES: To describe the initial clinical response and care escalation needs for children with urinary tract infections (UTIs) resistant to third-generation cephalosporins while on discordant antibiotics. METHODS: We performed a retrospective study of children <18 years old presenting to an acute care setting of 5 children's hospitals and a large managed care organization from 2012 to 2017 with third-generation cephalosporin-resistant UTIs (defined as the growth of ≥50 000 colony-forming units per mL of Escherichia coli or Klebsiella spp. nonsusceptible to ceftriaxone with a positive urinalysis). We included children started on discordant antibiotics who had follow-up when culture susceptibilities resulted. Outcomes were escalation of care (emergency department visit, hospital admission, or ICU transfer while on discordant therapy) and clinical response at follow-up (classified as improved or not improved). RESULTS: Of the 316 children included, 78% were girls and the median age was 2.4 years (interquartile range 0.6-6.5). Children were evaluated in the emergency department (56%) or clinic (43%), and 90% were started on a cephalosporin. A total of 7 of 316 children (2.2%; 95% confidence interval 0.8%-4.5%) experienced escalation of care. For the 230 children (73%) with clinical response recorded, 192 of 230 (83.5%; 95% confidence interval 78.0%-88.0%) experienced clinical improvement. In children with repeat urine testing while on discordant therapy, pyuria improved or resolved in 16 of 19 (84%) and urine cultures sterilized in 11 of 17 (65%). CONCLUSIONS: Most children with third-generation cephalosporin-resistant UTIs started on discordant antibiotics experienced initial clinical improvement, and few required escalation of care. Our findings suggest that narrow-spectrum empiric therapy is appropriate while awaiting final urine culture results.

Epidemiology of Cerebrospinal Fluid Cultures and Time to Detection in Term Infants.

BACKGROUND: Although meningitis is rare in previously healthy term infants, lumbar puncture is often performed to evaluate for source of illness. This study was performed to determine the time to detection for positive cerebrospinal fluid (CSF) cultures and to provide an update on the current epidemiology of bacterial meningitis in term infants. METHODS: This study was a multicenter, retrospective review of positive CSF cultures in infants ≤90 days of age. Specimens were drawn in the emergency department or inpatient setting between January 2000 and December 2013. Cultures were deemed true pathogens or contaminant species based on the attending physician's treatment plan. Cultures from premature infants, an operative source, or those with significant medical history were excluded. RESULTS: A total of 410 positive CSF culture results were included, with 53 (12.9%) true pathogens and 357 (87.1%) contaminant species. The mean ± SD time to detection for true pathogens was 28.6 ± 16.8 hours (95% confidence interval, 24-33.2); for contaminant species, it was 68.1 ± 36.2 hours (95% confidence interval, 64.3-71.9). Forty-three true-positive cases (81.1%) were positive in ≤36 hours. The most common pathogen was group B Streptococcus (51%), followed by Escherichia coli (13%) and Streptococcus pneumoniae (9%). CONCLUSIONS: The majority of pathogenic bacteria in CSF exhibit growth within 36 hours. Most growth from CSF cultures in febrile infants is treated as contamination. The epidemiology of meningitis has remained constant, with group B Streptococcus as the predominant pathogen, despite changes noted in the epidemiology of bacteremia in this population.

Urinary Imaging Findings in Young Infants With Bacteremic Urinary Tract Infection.

OBJECTIVES: To describe renal ultrasound (RUS) and voiding cystourethrogram (VCUG) findings and determine predictors of abnormal imaging in young infants with bacteremic urinary tract infection (UTI). METHODS: We used retrospective data from a multicenter sample of infants younger than 3 months with bacteremic UTI, defined as the same pathogenic organism in blood and urine. Infants were excluded if they had any major comorbidities, known urologic abnormalities at time of presentation, required intensive unit care, or had no imaging performed. Imaging results as stated in the radiology reports were categorized by a pediatric urologist. RESULTS: Of the 276 infants, 19 were excluded. Of the remaining 257 infants, 254 underwent a RUS and 224 underwent a VCUG. Fifty-five percent had ≥1 RUS abnormalities. Thirty-four percent had ≥1 VCUG abnormalities, including vesicoureteral reflux (VUR, 27%), duplication (1.3%), and infravesicular abnormality (0.9%). Age <1 month, male sex, and non-Escherichia coli organism predicted an abnormal RUS, but only non-E coli organism predicted an abnormal VCUG. Seventeen of 96 infants (17.7%) with a normal RUS had an abnormal VCUG: 15 with VUR (Grade I-III = 13, Grade IV = 2), 2 with elevated postvoid residual, and 1 with infravesical abnormality. CONCLUSIONS: Although RUS and VCUG abnormalities were common in this cohort, the frequency and severity were similar to previous studies of infants with UTIs in general. Our findings do not support special consideration of bacteremia in imaging decisions for otherwise well-appearing young infants with UTI.

Bacteraemic urinary tract infection: management and outcomes in young infants.

OBJECTIVES: To determine predictors of parenteral antibiotic duration and the association between parenteral treatment duration and relapses in infants <3 months with bacteraemic urinary tract infection (UTI). DESIGN: Multicentre retrospective cohort study. SETTING: Eleven healthcare institutions across the USA. PATIENTS: Infants <3 months of age with bacteraemic UTI, defined as the same pathogenic organism isolated from blood and urine. MAIN OUTCOME MEASURES: Duration of parenteral antibiotic therapy, relapsed UTI within 30 days. RESULTS: The mean (±SD) duration of parenteral antibiotics for the 251 included infants was 7.8 days (±4 days), with considerable variability between institutions (mean range 5.5-12 days). Independent predictors of the duration of parenteral antibiotic therapy included (coefficient, 95% CI): age (-0.2 days, -0.3 days to -0.08 days, for each week older), year treated (-0.2 days, -0.4 to -0.03 days for each subsequent calendar year), male gender (0.9 days, 0.01 to 1.8 days), a positive repeat blood culture during acute treatment (3.5 days, 1.2-5.9 days) and a non-Escherichia coli organism (2.2 days, 0.8-3.6 days). No infants had a relapsed bacteraemic UTI. Six infants (2.4%) had a relapsed UTI (without bacteraemia). The duration of parenteral antibiotics did not differ between infants with and without a relapse (8.2 vs 7.8 days, p=0.81). CONCLUSIONS: Parenteral antibiotic treatment duration in young infants with bacteraemic UTI was variable and only minimally explained by measurable patient factors. Relapses were rare and were not associated with treatment duration. Shorter parenteral courses may be appropriate in some infants.

Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children.

IMPORTANCE: Postdischarge treatment of acute osteomyelitis in children requires weeks of antibiotic therapy, which can be administered orally or intravenously via a peripherally inserted central catheter (PICC). The catheters carry a risk for serious complications, but limited evidence exists on the effectiveness of oral therapy. OBJECTIVE: To compare the effectiveness and adverse outcomes of postdischarge antibiotic therapy administered via the PICC or the oral route. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study comparing PICC and oral therapy for the treatment of acute osteomyelitis. Among children hospitalized from January 1, 2009, through December 31, 2012, at 36 participating children's hospitals, we used discharge codes to identify potentially eligible participants. Results of medical record review confirmed eligibility and defined treatment group allocation and study outcomes. We used within- and across-hospital propensity score-based full matching to adjust for confounding by indication. INTERVENTIONS: Postdischarge administration of antibiotics via the PICC or the oral route. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure. Secondary outcomes included adverse drug reaction, PICC line complication, and a composite of all 3 end points. RESULTS: Among 2060 children and adolescents (hereinafter referred to as children) with osteomyelitis, 1005 received oral antibiotics at discharge, whereas 1055 received PICC-administered antibiotics. The proportion of children treated via the PICC route varied across hospitals from 0 to 100%. In the across-hospital (risk difference, 0.3% [95% CI, -0.1% to 2.5%]) and within-hospital (risk difference, 0.6% [95% CI, -0.2% to 3.0%]) matched analyses, children treated with antibiotics via the oral route (reference group) did not experience more treatment failures than those treated with antibiotics via the PICC route. Rates of adverse drug reaction were low (<4% in both groups) but slightly greater in the PICC group in across-hospital (risk difference, 1.7% [95% CI, 0.1%-3.3%]) and within-hospital (risk difference, 2.1% [95% CI, 0.3%-3.8%]) matched analyses. Among the children in the PICC group, 158 (15.0%) had a PICC complication that required an emergency department visit (n = 96), a rehospitalization (n = 38), or both (n = 24). As a result, the PICC group had a much higher risk of requiring a return visit to the emergency department or for hospitalization for any adverse outcome in across-hospital (risk difference, 14.6% [95% CI, 11.3%-17.9%]) and within-hospital (risk difference, 14.0% [95% CI, 10.5%-17.6%]) matched analyses. CONCLUSIONS AND RELEVANCE: Given the magnitude and seriousness of PICC complications, clinicians should reconsider the practice of treating otherwise healthy children with acute osteomyelitis with prolonged intravenous antibiotics after hospital discharge when an equally effective oral alternative exists.

Epidemiology of bacteremia in febrile infants in the United States.

BACKGROUND: Fever in infants is a common clinical dilemma. The objective of this study was to present data from hospital systems across the northeast, southeast, mid-west, and western United States to identify the pathogens causing bacteremia in febrile infants admitted to general care units. METHODS: This was a retrospective review of positive blood culture results in febrile infants aged ≤90 days admitted to a general care unit across 6 hospital systems. Data were collected from January 1, 2006 through December 31, 2012 from emergency departments and general inpatient units. Cultures from ICUs, central lines, or infants who had complex comorbidities were excluded, as were repeat cultures positive for the same bacteria. Common contaminants were considered pathogens if they were treated as such. RESULTS: We identified 181 cases of bacteremia in 177 infants. The most common pathogen was Escherichia coli (42%), followed by group B Streptococcus (23%). Streptococcus pneumoniae was more likely in older infants (P = .01). Non-low-risk bacteremic infants were more likely to have E. coli or group B Streptococcus than low-risk bacteremic infants. We identified no cases of Listeria monocytogenes. Variation between sites was minimal. CONCLUSIONS: This is the largest and most geographically diverse study to date examining the epidemiology of bacteremia in infants. We suggest E. coli is the most common cause of bacteremia in previously healthy febrile infants admitted to a general inpatient unit. We identified no cases of L monocytogenes and question whether empirical therapy remains necessary for this pathogen.

Intravenous delivery of cysteamine for the treatment of cystinosis: association with hepatotoxicity.

Nephropathic cystinosis is a lysosomal storage disorder, which, if untreated, results in renal failure by age 10 years. Oral cysteamine has been shown to preserve renal function in these patients. In this study, a 2-year-old girl with nephropathic cystinosis and severe gastrointestinal dysmotility was treated with intravenous (i.v.) administration of cysteamine hydrochloride (HCl). This is only the second report of long-term i.v. cysteamine therapy for nephropathic cystinosis. Unlike the treatment in the previous case, however, treatment in our patient was limited by liver toxicity.