Improving Oral Health and Modulating the Oral Microbiome to Reduce Bloodstream Infections from Oral Organisms in Pediatric and Young Adult Hematopoietic Stem Cell Transplantation Recipients: A Randomized Controlled Trial

Abstract

Bloodstream infections (BSIs) from oral organisms are a significant cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. There are no proven strategies to decrease BSIs from oral organisms. The aim of this study was to evaluate the impact of daily xylitol wipes in improving oral health, decreasing BSI from oral organisms, and modulating the oral microbiome in pediatric HSCT recipients. This was a single-center 1:1 randomized controlled trial in pediatric HSCT recipients age >2 years. Age-matched healthy children were enrolled to compare the oral microbiome. The oral hygiene standard of care (SOC) group continued to receive the standard oral hygiene regimen. The xylitol group received daily oral xylitol wipes (with .7 g xylitol) in addition to the SOC. The intervention started from the beginning of the transplantation chemotherapy regimen and extended to 28 days following transplantation. The primary outcome was oral health at interval time points, and secondary outcomes included BSIs from oral organisms in the first 30 days following transplantation, oral microbiome abundance, and diversity and oral pathogenic organism abundance. The study was closed early due to efficacy after an interim analysis of the first 30 HSCT recipients was performed (SOC group, n = 16; xylitol group, n = 14). The xylitol group had a significantly lower rate of gingivitis at days 7, 14, and 28 following transplantation (P = .031, .0039, and .0005, respectively); oral plaque at days 7 and 14 (P = .045 and .0023, respectively); and oral ulcers >10 mm at day 14 (P = .049) compared with the SOC group. The xylitol group had no BSI from oral organisms compared with the SOC group, which had 4 (P = .04). The xylitol group had significantly lower abundance of potential BSI pathogens, such as Staphylococcus aureus (P = .036), Klebsiella pneumoniae (P = .033), and Streptococcus spp (P = .011) at the day after transplantation compared with the SOC group. Healthy children and young adults had significantly increased oral microbiome diversity compared with all HSCT recipients (P < .001). The addition of xylitol to standard oral care significantly improves oral health, decreases BSI from oral organisms, and decreases the abundance of pathogenic oral organisms in pediatric and young adult HSCT recipients.

Keywords: Bloodstream infection; Hematopoietic stem cell transplantation; Microbiome; Mucosal barrier injury laboratory-confirmed bloodstream infection; Xylitol.

Figure 1.

Study participation and trial flow. Thirty-five study subjects were enrolled in the study: 18 in the SOC group, 17 in the xylitol group, and 30 healthy children and young adults. Two of the 18 subjects randomized to the SOC group and 3 of the 17 subjects randomized to the Xylitol group withdrew from the study; thus, the study analysis included 16 subjects in the SOC group and 14 subjects in the xylitol group.

Figure 2.

Comparison of oral hygiene in randomized to the xylitol group (n = 14) or the SOC group (n = 16). Compared with HSCT recipients in the SOC group, HSCT recipients in the xylitol group had decreased gingivitis at days 7, 14, and 28 post-transplantation; decreased oral plaque at days 7 and 14 post-transplantation; and fewer oral ulcers >10 mm at day 14 post-transplantation.

Figure 3.

(A) Comparison of the oral microbiome species abundance and diversity in HSCT recipients at baseline (before transplantation chemotherapy) (n = 30) and healthy age-matched children and young adults (n = 30). (B) There was an increase abundance of commensal oral organisms in healthy children and young adults compared with all HSCT recipients. (C) There was an increase abundance of potential pathogenic oral organisms in all HSCT recipients compared with healthy children and young adults.

Figure 4.

(A) Species abundance at baseline (before the start of the transplantation chemotherapy regimen in the SOC and xylitol groups. (B) (1) Increased pathogenic species abundance at baseline and days 7, 14, 28 post-transplantation in the SOC group compared with the xylitol group. (2) Increased Streptococcus spp abundance (oral pathogenic bacteria) at day 7 post-transplantation in the SOC group compared with the xylitol group. (3) Increased fungal species abundance at days 7, 14, and 28 post-transplantation in the SOC group compared with the Xylitol group.