Appropriateness of Antibiotic Prescribing in United States Children's Hospitals: A National Point Prevalence Survey.

BACKGROUND: Studies estimate that 30%-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children is needed to guide pediatric antimicrobial stewardship. METHODS: Cross-sectional analysis of antibiotic prescribing at 32 children's hospitals in the United States. Subjects included hospitalized children with ≥ 1 antibiotic order at 8:00 am on 1 day per calendar quarter, over 6 quarters (quarter 3 2016-quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification. RESULTS: Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥ 1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥ 1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis > 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders. CONCLUSIONS: Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving 1 or more antibiotics at any given time. One-quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.

Reducing length of antibiotics for children with ear infections: protocol for a cluster-randomized trial in the USA.

Aim: Preventing unnecessarily long durations of antibiotic therapy is a key opportunity to reduce antibiotic overuse in children 2 years of age and older with acute otitis media (AOM). Pragmatic interventions to reduce durations of therapy that can be effectively scaled and sustained are urgently needed. This study aims to fill this gap by evaluating the effectiveness and implementation outcomes of two low-cost interventions of differing intensities to increase guideline-concordant antibiotic durations in children with AOM. Methods: The higher intensity intervention will consist of clinician education regarding guideline-recommended short durations of antibiotic therapy; electronic health record (EHR) prescription field changes to promote prescribing of recommended short durations; and individualized clinician audit and feedback on adherence to recommended short durations of therapy in comparison to peers, while the lower intensity intervention will consist only of clinician education and EHR changes. We will explore the differences in implementation effectiveness by patient population served, clinician type, clinical setting and organization as well as intervention type. The fidelity, feasibility, acceptability and perceived appropriateness of the interventions among different clinician types, patient populations, clinical settings and intervention type will be compared. We will also conduct formative qualitative interviews with clinicians and administrators and focus groups with parents of patients to further inform the interventions and study. The formative evaluation will take place over 1.5 years, the interventions will be implemented over 2 years and evaluation of the interventions will take place over 1.5 years. Discussion: The results of this study will provide a framework for other healthcare systems to address the widespread problem of excessive durations of therapy for AOM and inform national antibiotic stewardship policy development. Clinical Trial Registration: NCT05608993 (ClinicalTrials.gov).

Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection.

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) catalyzes the first step of tryptophan (Trp) catabolism, yielding kynurenine (Kyn) metabolites. The kynurenine-to-tryptophan (K/T) ratio is used as a surrogate for biological IDO enzyme activity. IDO expression is increased during Escherichia coli urinary tract infection (UTI). Thus, our objective was to develop a method for measurement of Kyn/Trp ratio in human blood and urine and evaluate its use as a biomarker of UTI. METHODS: A mass spectrometric method was developed to measure Trp and Kyn in serum and urine specimens. The method was applied to clinical urine specimens from symptomatic pediatric patients with laboratory-confirmed UTI or other acute conditions and from healthy controls. RESULTS: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was linear to 500 µmol/L for both Trp and Kyn. Imprecision ranged from 5 to 15% for Trp and 6-20% for Kyn. Analytical recoveries of Trp and Kyn ranged from 96 to 119% in serum and 90-97% in urine. No correlation was found between the K/T ratio and circulating IDO mass (r = 0.110) in serum. Urinary Kyn and Trp in the pediatric test cohort demonstrated elevations in the K/T ratio in symptomatic patients with UTI (median 13.08) and without UTI (median 14.38) compared to healthy controls (median 4.93; p < 0.001 for both comparisons). No significant difference in K/T ratio was noted between symptomatic patients with and without UTI (p = 0.84). CONCLUSIONS: Measurement of Trp and Kyn by LC-MS/MS is accurate and precise in serum and urine specimens. While urinary K/T ratio is not a specific biomarker for UTI, it may represent a general indicator of a systemic inflammatory process.

Clinical trials in children--How are they implemented?

Drug metabolism in children may differ from adults and adverse events may occur that are not predictable from the adult experience. Clinical trials of safety and efficacy are needed both for new treatments and those that may already be in use but have not been tested in infants and children. The role and responsibilities of different participants in a trial are discussed, including the steering committee, the clinical and statistical co-ordinating centers, and the data and safety monitoring board. Advantages of external vs internal pilot studies are reviewed. Information that is available on the websites of the Food and Drug Administration and the National Institute of Neurological Disorders and Stroke may be helpful to those planning clinical trials of interventions in children.