Gastrointestinal Graft-versus-Host Disease Is a Risk Factor for Postengraftment Bloodstream Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Mori, Yasuo; Yoshimoto, Goichi; Nishida, Ruriko; Sugio, Takeshi; Miyawaki, Kohta; Shima, Takahiro; Nagasaki, Yoji; Miyake, Noriko; Harada, Yukiko; Kunisaki, Yuya; Kamezaki, Kenjiro; Numata, Akihiko; Katô, Kôji; Shiratsuchi, Motoaki; Maeda, Takahiro; Takenaka, Katsuto; Iwasaki, Hiromi; Shimono, Nobuyuki; Akashi, Koichi; Miyamoto, Toshihiro

doi:10.1016/j.bbmt.2018.06.002

Cited by 26 publications

(30 citation statements)

References 39 publications

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“…A Cox proportional hazard regression analysis was performed to estimate adjusted hazard ratio and 95% CIs. The risk status at transplantation was classified based on the criteria described previously [32].…”

Section: Discussionmentioning

confidence: 99%

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation

et al. 2020

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Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1-V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome. PLOS PATHOGENSPLOS Pathogens | https://doi.org/10.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are subjected to intensive chemotherapy, irradiation and antibiotics which could affect the intestinal as well as oral microbiota. We employed full-length 16S rRNA gene sequencing analysis with high taxonomic resolution using a third-generation sequencer, PacBio Sequel, and determined the bacterial composition of the tongue microbiota of allo-HSCT recipients after conditioning regimens. This comprehensive molecular approach identified 34 taxa uncommon in the oral cavity, which constituted 0-99.4% (median, 0.27%) of each tongue microbiota. Of them, Staphylococcus haemolyticus and Ralstonia pickettii were frequently found in allo-HSCT recipients, and their detection was significantly associated with a higher risk of mortality during the follow-up period. These results suggest that careful attention should be given to the bacterial composition of the disrupted oral microbiota in allo-HSCT recipients. PLOS PATHOGENSDisrupted oral microbiota of allo-HSCT recipients PLOS Pathogens | https://doi.org/10.

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Section: Discussionmentioning

confidence: 99%

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation

et al. 2020

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“…Nevertheless, in this study, authors did not find any case of S aureus bloodstream infection even in colonized patients, and it remains more probable that the low rate of S aureus infection observed is correlated with good hygiene practices regarding catheter manipulation. The high rates of gram‐negative bacterial infections observed in the late phase are probably related to gastrointestinal translocation due to GvHD, 31 as only one center gave quinolone prophylaxis during episodes of digestive GvHD. Finally, according to the absence of obligate anaerobe coverage by the polymyxin‐neomycin regimen, 32 anaerobes accounted for up to 11.2% of bacterial infection during the pre‐engraftment period.…”

Section: Discussionmentioning

confidence: 99%

Microbiologically documented infections after adult allogeneic hematopoietic cell transplantation: A 5‐year analysis within the Swiss Transplant Cohort study

Dayer

Masouridi‐Levrat

et al. 2020

Transplant Infectious Dis

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Background Infections are an important complication after allogeneic hematopoietic cell transplantation (allo‐HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo‐HCT patients, as well as associated risk factors for infections and for one‐year non‐relapse mortality. Methods This is a retrospective cohort study using STCS and EBMT databases to assess the one‐year incidence rate of infection, as well as risk factors for infections and for one‐year non‐relapse mortality among adult allo‐HCT patients transplanted between 2010 and 2014 in Switzerland. Univariable and multivariable quasi‐Poisson and multivariable Cox regression models were used. Results Of 553 patients included, 486 had an infection with a global incidence rate of 3.66 infections per patient‐year. Among a total of 1534 infections analyzed, viral infections were predominant (n = 1138, 74.2%), followed by bacterial (n = 343, 22.4%) and fungal (n = 53, 3.5%) infections. At one year, the cumulative incidence of relapse and non‐relapse mortality was 26% and 16%, respectively. 195 (35.3%) of patients had at least one episode of severe graft‐versus‐host‐disease (GvHD). A center effect was observed, and underlying disease, donor type, cytomegalovirus serological constellation, and GvHD were also associated with the incidence rate of infections. There was an increased risk for one‐year non‐relapse mortality associated with all pathogens, specifically within two months of infection, and this remained true beyond 2 months of a fungal infection. Conclusion Despite advances to limit infections in this population, they still occur in most allo‐HCT patients with a major impact on survival at 1 year.

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“…Recently, Mori et al published a retrospective chart review of 316 Japanese adult allo HSCT recipients, 43 of whom developed a total of 57 BSI episodes in the post‐engraftment period until day 180 post‐transplantation. Acute GVHD (GI or non‐GI) experienced throughout the post‐engraftment course was associated with BSI risk and increasing grades of GVHD (grades 3 and 4) were associated with increasing BSI risk.…”

Section: Discussionmentioning

confidence: 99%

Severity of acute gastrointestinal graft‐vs‐host disease is associated with incidence of bloodstream infection after adult allogeneic hematopoietic stem cell transplantation

Modi

Rybicki

Majhail

et al. 2019

Transplant Infectious Dis

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Background Infections are the most common cause of non‐relapse mortality in adult allogeneic hematopoietic stem cell transplant (allo HSCT) recipients. Acute gastrointestinal graft‐vs‐host disease (GI GVHD) often leads to friable mucosa as well as treatment interventions which can increase risk of infection. Our primary objective was to describe the relationship between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI). Methods We reviewed 441 adults who underwent allo HSCT from 2011 to 2017 and were clinically diagnosed with GI GVHD, non‐GI GVHD, or no GVHD based on the modified Glucksberg scale within the first 100 days of transplantation. The maximum grades of acute GI GVHD and non‐GI GVHD were used in the analysis. BSI was defined based on the presence of a blood culture positive for bacteria or fungi and treatment with antibiotics. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Fine and Gray regression was used to assess association between clinical grade of acute GI GVHD and BSI risk, adjusting for grade of non‐GI GVHD and for other significant baseline patient risk factors for BSI identified by multivariable analysis. Results are shown as hazard ratio (HR) and 95% confidence interval (CI). A similar analysis was conducted in 130 patients with histologic grade of acute GI GVHD. Results Overall BSI incidence by day 180 was 32%; gram‐negative bacilli were the predominant organisms, followed by gram‐positive cocci and fungi. Patients with grade 4 acute GI GVHD had higher risk of BSI as compared to patients with no GI GVHD (HR 2.98, CI 1.65‐5.37, P < .001), while those with grade 3 acute GI GVHD had similar BSI risk (HR 0.89, CI 0.36‐2.21, P = .81). Grade of GI GVHD had no association with risk of non‐BSI. Results were similar in patients with histologic grade acute GI GVHD. Patients who developed BSI or non‐BSI had significantly higher overall mortality risk compared to those without infectious complications (HR 2.52, CI 1.92‐3.31, P < .001 for BSI; HR 1.60, CI 1.20‐2.13, P = .001 for non‐BSI). Conclusions Grade 4 acute GI GVHD is associated with a higher risk of BSI, which is in turn associated with a higher risk of overall mortality in this population. Understanding the relationships between acute GI GVHD, BSI, and overall mortality can guide future treatment strategies for adult allo HSCT recipients.

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Gastrointestinal Graft-versus-Host Disease Is a Risk Factor for Postengraftment Bloodstream Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Cited by 26 publications

References 39 publications

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation

Microbiologically documented infections after adult allogeneic hematopoietic cell transplantation: A 5‐year analysis within the Swiss Transplant Cohort study

Severity of acute gastrointestinal graft‐vs‐host disease is associated with incidence of bloodstream infection after adult allogeneic hematopoietic stem cell transplantation

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