Antibiotic-associated neutropenia is marked by depletion of intestinal Lachnospiraceae in pediatric patients.

Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae . Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance. Key Points: Neutropenia occurred in 17% of patients receiving prolonged antibiotic therapy.We found no association between neutropenia and type of infection or class of antibiotic used. Development of neutropenia after prolonged antibiotic treatment was associated with decreased prevalence of Lachnospiraceae and Lachnospiraceae metabolites such as citrulline.

Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease.

ABSTRACT: Over the past 10 years, there has been a marked increase in recognition of the interplay between the intestinal microbiome and the hematopoietic system. Despite their apparent distance in the body, a large literature now supports the relevance of the normal intestinal microbiota to steady-state blood production, affecting both hematopoietic stem and progenitor cells as well as differentiated immune cells. Microbial metabolites enter the circulation where they can trigger cytokine signaling that influences hematopoiesis. Furthermore, the state of the microbiome is now recognized to affect outcomes from hematopoietic stem cell transplant, immunotherapy, and cellular therapies for hematologic malignancies. Here we review the mechanisms by which microbiotas influence hematopoiesis in development and adulthood as well as the avenues by which microbiotas are thought to impact stem cell transplant engraftment, graft-versus-host disease, and efficacy of cell and immunotherapies. We highlight areas of future research that may lead to reduced adverse effects of antibiotic use and improved outcomes for patients with hematologic conditions.

Timely Delivery of Discharge Medications to Patients' Bedsides: A Patient-centered Quality Improvement Project.

INTRODUCTION: Patients who are unable to fill prescriptions after discharge are at risk of hospital readmission. Ensuring that patients have prescriptions in hand at the time of discharge is a critical component of a safe and effective discharge process. Using a "Meds to Beds" program, we aimed to increase the percentage of patients discharged from Holtz Children's Hospital with medications in hand from 49% to 80%, reduce turnaround time (TAT) from electronic prescription signature to bedside delivery from 4.9 hours (±2.6 hours) to 2 hours, and increase caregiver satisfaction. METHODS: We formed a multidisciplinary team and implemented 4 patient-centered interventions through iterative plan-do-study-act cycles. Statistical process control charts were used to understand the impact of the interventions over 10 months. Hospital length of stay and discharges before 2:00 pm were used as balancing measures. We measured caregiver satisfaction using a telephone survey administered by pediatric residents within 7 days after discharge. RESULTS: The mean percentage of patients discharged with medications in hand increased to 76%. TAT decreased to 3.5 hours (±1.8 hours). Length of stay did not significantly increase, whereas the percentage of patients discharged before 2:00 pm did. Caregivers of patients who had prescriptions delivered to their bedside reported high levels of satisfaction. CONCLUSIONS: Using a "Meds to Beds" program, we increased the percentage of patients discharged with medications in hand, decreased TAT with reduced variability, and achieved high levels of caregiver satisfaction. Importantly, there was a shift in the culture of the institution toward improved medication access for patients.

Unilateral lung agenesis, hiatal hernia and atrioventricular septal defect: a rare combination of congenital anomalies.

Unilateral lung agenesis is a relatively rare congenital anomaly with a reported incidence of 1 in 15 000 births. It is frequently associated with other congenital malformations. Some of the sequelae of lung agenesis are potentially life-threatening. Here, we report a case of left lung agenesis in association with hiatal hernia and atrioventricular septal defect, a rare combination of anomalies which have not been described previously in the literature.