The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for b-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.

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A B S T R A C T Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18 years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year allcause and cause-specific mortality during 3 time periods based on year of transplantation (). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P = .0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P = .06) or graft failure (9% versus 3%; P = .01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequent infectious causes of death in children after UCBT. Advances in clinical practice over the past 20 years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.

Infections in children and adolescents with cancer are a significant cause of morbidity and mortality, especially in those receiving chemotherapy who are neutropenic and/or immunocompromised. The aim of this article is to review existing evidence in order to provide a practice recommendation to prevent or minimize infections in neutropenic and/or immunocompromised patients receiving chemotherapy and/or stem cell transplant. Systematic reviews were undertaken and research was graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. A variety of interventions are implemented to reduce infections in the neutropenic and/or immunocompromised population; however, few are supported by research evidence. Existing literature should continue to be reviewed to further identify interventions that can influence positive patient outcomes and provide opportunities for individuals in the medical field to work together to improve clinical care.

Respiratory viral infections (RVI) are a frequent cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) patients. We examined clinical characteristics and respiratory viral detection in asymptomatic pediatric HSCT pre-transplant patients and symptomatic post-transplant patients. Coxsackie/echovirus (most common virus detected pre and post-transplant), rhinovirus, and coronavirus were detected pre-transplant and at the first post-transplant event suggesting persistent detection. None of the clinical characteristics examined were associated with viral detection and there was no increase in mortality noted with asymptomatic viral detection.