Microbiology of Bloodstream Infections in Children After Hematopoietic Stem Cell Transplantation: A Single-Center Experience Over Two Decades (1997–2017)

Abstract

Background Bloodstream infections (BSI) occur frequently after hematopoietic stem cell transplantation (HSCT). We examined the microbiology of BSI in pediatric HSCT recipients over a two-decade period at our institution to inform empirical antimicrobial prescribing and infection prevention strategies. Methods We conducted a retrospective cohort study of children (<18 years) who underwent HSCT at Duke University between 1997 and 2015. We used recurrent-event gap-time Cox proportional hazards models to determine the hazards of all-cause and cause-specific BSI according to HSCT year. We compared the median time to BSI by causative organism type and evaluated for temporal trends in the prevalence of antibiotic resistance among causative organisms. Results A total of 865 BSI occurred in 1311 children, including 412 (48%) Gram-positive bacterial, 196 (23%) Gram-negative bacterial, 56 (6%) fungal, 23 (3%) mycobacterial, and 178 (21%) polymicrobial BSI. The hazard of all BSI did not change substantially over time during the study period, but the hazard of fungal BSI declined over time during the study period (p=0.04). Most fungal BSI (82%) occurred in the first 100 days after HSCT, while mycobacterial BSI occurred later after HSCT than BSI caused by other organisms (p<0.0001). The prevalence of vancomycin resistance among BSI caused by Enterococcus faecium increased during the study period (p=0.0007). The risk of two-year mortality in children was increased with BSI (p=0.02), Gram-negative bacterial BSI (p=0.02), and fungal BSI (p<0.0001). Conclusions Despite expanded practices for BSI prevention over the past several decades, the incidence of BSI remains high in pediatric HSCT recipients at our institution. Additional strategies are urgently needed to effectively prevent BSI in this high-risk population.

Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation

“…A median of seven stools (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] were collected per patient starting pre-transplant through one-year post-transplant. 76% of the stool samples were collected within the first 30 days after HCT (Supplemental Figure 2).…”

“…While aGVHD is the most prevalent and fatal treatment-related complication of HCT, bloodstream infections (BSI) are also an important cause of treatment-related morbidity and mortality in patients undergoing allo-HCT. The cumulative incidence of BSI in pediatric HCT patients is ~20% in the first 100 days (12) (ranging from 15% to 65% (12)(13)(14)(15)(16)), with 18% BSI-attributable mortality (range, 12% to 20%) (12), and an estimated healthcare cost of $40,000-$70,000 per BSI incident (13,17). In adult HCT patients, a diverse gut microbiome is associated with a lower risk of chemotherapy-related BSI (16).…”

Randomized controlled trial of gut decontamination in pediatric patients undergoing allogeneic hematopoietic cell transplantation

“…The copyright holder for this this version posted December 17, 2021. ; https://doi.org/10.1101/2021.12. 16.21267940 doi: medRxiv preprint…”

“…Most patients had underlying hematologic malignancies (n=15), received myeloablative conditioning regimens (n=17), and had bone marrow as the graft source (n=19). A median of seven stools per patient per transplant (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] were collected starting pre-transplant through one-year posttransplant. 76% of the stool samples were collected within the first 30 days after HCT (Supplemental Figure 3).…”

“…While aGVHD is the most prevalent and fatal treatment related complication of HCT, bloodstream infections (BSI) are also an important cause of treatment-related morbidity and mortality in patients undergoing allo-HCT. The cumulative incidence of BSI in pediatric HCT patients is approximately 20% in the first 100 days [13] (ranging from 15% to 65% [13][14][15][16][17]), with 18% BSIattributable mortality (range 12% to 20%) [13], and an estimated healthcare cost of $40,000 to $70,000 per BSI incident [14,18]. In adult HCT patients, a diverse gut microbiome is associated with a lower risk of chemotherapy-related BSI during HCT [17].…”