A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

A qualitative assessment of nonclinical drivers of pediatric outpatient antibiotic prescribing: The importance of continuity.

Background and objectives: Antibiotic overuse is common in outpatient pediatrics and varies across clinical setting and clinician type. We sought to identify social, behavioral, and environmental drivers of outpatient antibiotic prescribing for pediatric patients. Methods: We conducted semistructured interviews with physicians and advanced practice providers (APPs) across diverse outpatient settings including pediatric primary, urgent, and retail care. We used the grounded theory constant comparative method and a thematic approach to analysis. We developed a conceptual model, building on domains of continuity to map common themes and their relationships within the healthcare system. Results: We interviewed 55 physicians and APPs. Clinicians across all settings prioritized provision of guideline-concordant care but implemented these guidelines with varying degrees of success. The provision of guideline-concordant care was influenced by the patient-clinician relationship and patient or parent expectations (relational continuity); the clinician's access to patient clinical history (informational continuity); and the consistency of care delivered (management continuity). No difference in described themes was determined by setting or clinician type; however, clinicians in primary care described having more reliable relational and informational continuity. Conclusions: Clinicians described the absence of long-term relationships (relational continuity) and lack of availability of prior clinical history (informational continuity) as factors that may influence outpatient antibiotic prescribing. Guideline-concordant outpatient antibiotic prescribing was facilitated by consistent practice across settings (management continuity) and the presence of relational and informational continuity, which are common only in primary care. Management continuity may be more modifiable than informational and relational continuity and thus a focus for outpatient stewardship programs.

Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema.

BACKGROUND: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. METHODS: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. RESULTS: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. CONCLUSION: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

Population-based assessment of patient and provider characteristics influencing pediatric outpatient antibiotic use in a high antibiotic-prescribing state.

OBJECTIVE: To identify patient and provider characteristics associated with high-volume antibiotic prescribing for children in Tennessee, a state with high antibiotic utilization. DESIGN: Cross-sectional, retrospective analysis of pediatric (aged <20 years) outpatient antibiotic prescriptions in Tennessee using the 2016 IQVIA Xponent (formerly QuintilesIMS) database. METHODS: Patient and provider characteristics, including county of prescription fill, rural versus urban county classification, patient age group, provider type (nurse practitioner, physician assistant, physician, or dentist), physician specialty, and physician years of practice were analyzed. RESULTS: Tennessee providers wrote 1,940,011 pediatric outpatient antibiotic prescriptions yielding an antibiotic prescribing rate of 1,165 per 1,000 population, 50% higher than the national pediatric antibiotic prescribing rate. Mean antibiotic prescribing rates varied greatly by county (range, 39-2,482 prescriptions per 1,000 population). Physicians wrote the greatest number of antibiotic prescriptions (1,043,030 prescriptions, 54%) of which 56% were written by general pediatricians. Pediatricians graduating from medical school prior to 2000 were significantly more likely than those graduating after 2000 to be high antibiotic prescribers. Overall, 360 providers (1.7% of the 21,798 total providers in this dataset) were responsible for nearly 25% of both overall and broad-spectrum antibiotic prescriptions; 20% of these providers practiced in a single county. CONCLUSIONS: Fewer than 2% of providers account for 25% of pediatric antibiotic prescriptions. High antibiotic prescribing for children in Tennessee is associated with specific patient and provider characteristics that can be used to design stewardship interventions targeted to the highest prescribing providers in specific counties and specialties.