Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

2021

e29384

2021 Oct 28

1545-5017

<p><strong>BACKGROUND: </strong>The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed.</p>

<p><strong>METHODS: </strong>We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations.</p>

<p><strong>RESULTS: </strong>We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4&nbsp;days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition.</p>

<p><strong>DISCUSSION: </strong>Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.</p>

10.1002/pbc.29384

Pediatr Blood Cancer

34709713

Metric Development for the Multicenter Improving Pediatric Sepsis Outcomes (IPSO) Collaborative.

2021

2021 04 01

1098-4275

<p><strong>BACKGROUND: </strong>A 56 US hospital collaborative, Improving Pediatric Sepsis Outcomes, has developed variables, metrics and a data analysis plan to track quality improvement (QI)-based patient outcomes over time. Improving Pediatric Sepsis Outcomes expands on previous pediatric sepsis QI efforts by improving electronic data capture and uniformity across sites.</p>

<p><strong>METHODS: </strong>An expert panel developed metrics and corresponding variables to assess improvements across the care delivery spectrum, including the emergency department, acute care units, hematology and oncology, and the ICU. Outcome, process, and balancing measures were represented. Variables and statistical process control charts were mapped to each metric, elucidating progress over time and informing plan-do-study-act cycles. Electronic health record (EHR) abstraction feasibility was prioritized. Time 0 was defined as time of earliest sepsis recognition (determined electronically), or as a clinically derived time 0 (manually abstracted), identifying earliest physiologic onset of sepsis.</p>

<p><strong>RESULTS: </strong>Twenty-four evidence-based metrics reflected timely and appropriate interventions for a uniformly defined sepsis cohort. Metrics mapped to statistical process control charts with 44 final variables; 40 could be abstracted automatically from multiple EHRs. Variables, including high-risk conditions and bedside huddle time, were challenging to abstract (reported in &lt;80% of encounters). Size or type of hospital, method of data abstraction, and previous QI collaboration participation did not influence hospitals' abilities to contribute data. To date, 90% of data have been submitted, representing 200 007 sepsis episodes.</p>

<p><strong>CONCLUSIONS: </strong>A comprehensive data dictionary was developed for the largest pediatric sepsis QI collaborative, optimizing automation and ensuring sustainable reporting. These approaches can be used in other large-scale sepsis QI projects in which researchers seek to leverage EHR data abstraction.</p>

10.1542/peds.2020-017889

Pediatrics

33795482

Broad spectrum antibiotics and risk of graft-versus-host disease in pediatric patients transplanted for acute leukemia: association of carbapenem use with risk of acute GVHD.

2021

177.e1-177.e8

2021 Feb

2666-6367

<p>Variation in the gastrointestinal microbiota after hematopoietic cell transplantation has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD-risk in pediatric patients transplanted for acute leukemia. We performed a retrospective analysis in a dataset merged from two sources: (1) Center for International Blood and Marrow Transplant Research, an observational transplant registry, and (2) Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to three classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) anti-pseudomonal penicillins and (3) carbapenems. The primary outcome was grade 2-4 aGVHD; secondary outcomes were grade 3-4 aGVHD and lower gastrointestinal (GI) GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (sub-cohort) included transplant characteristics, GVHD-risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2,550 patients at 36 centers; the sub-cohort included 1,174 patients. In adjusted models, carbapenems were associated with an increased risk of grade 2-4 aGVHD in the full cohort (aOR 1.24, 95%CI 1.02-1.51) and sub-cohort (subHR 1.31, 95%CI 0.99-1.72), as well as with an increased risk of grade 3-4 aGVHD (subHR 1.77, 95%CI 1.25-2.52). Early carbapenem exposure (prior to day 0) especially impacted aGVHD-risk. For antipseudomonal penicillins the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad spectrum antibiotics, should be used judiciously in pediatric transplant patients to minimize aGVHD-risk. Further research is needed to clarify the mechanism underlying this association.</p>

10.1016/j.jtct.2020.10.012

Transplant Cell Ther

33718896

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

2021

2021 Jan

1098-4275

<p>Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.</p>

10.1542/peds.2020-1434

Pediatrics

33328337