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

Abstract

Background: Bloodstream infections (BSIs) occur frequently after hematopoietic stem cell transplantation (HSCT). We examined the microbiology of BSI in pediatric HSCT recipients over a 2-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 BSIs did not change substantially over time during the study period, but the hazard of fungal BSIs declined over time during the study period (P = .04). Most fungal BSIs (82%) occurred in the first 100 days after HSCT, whereas mycobacterial BSIs occurred later after HSCT than BSIs caused by other organisms (P < .0001). The prevalence of vancomycin resistance among BSIs caused by Enterococcus faecium increased during the study period (P = .0007). The risk of 2-year mortality in children was increased with BSI (P = .02), Gram-negative bacterial BSI (P = .02), and fungal BSI (P < .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 BSIs in this high-risk population.

Keywords: antibiotic resistance; bloodstream infections; hematopoietic stem cell transplantation; immunocompromised host; pediatrics.

Figure 1.

Forest plots for the risk of bloodstream infections (BSIs) among the study population by hematopoietic stem cell transplantation (HSCT) year. Forest plots of hazard ratios and 95% confidence interval bars with year category 1997–2000 serving as reference for the following: (A) all BSI, (B) Gram-positive bacterial BSI, (C) Gram-negative bacterial BSI, (D) fungal BSI, and (E) polymicrobial BSI.

Figure 2.

Timing of bloodstream infection (BSI) episodes relative to hematopoietic stem cell transplantation (HSCT). Violin plot depicting the time from HSCT to BSI by BSI category. Within the violin, we indicate the median and 25th and 75th percentiles. Bloodstream infection categories (Gram-positive bacterial, Gram-negative bacterial, fungal, mycobacterial, and polymicrobial) are mutually exclusive.