Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Atrouni, Wissam El; Shune, Leyla; Telfah, Mohammad; Gao, Guangyi; He, Jia; Abhyankar, Sunil; McGuirk, Joseph P.; Clough, Lisa M.

doi:10.1016/j.jtct.2020.10.009

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…Moreover, a statistically significant reduction of Clostridioides difficile by day +100 was observed moving from Cohort A to Cohort B (47% vs. 15%, p=0.04; Figure 2). This can be considered a direct effect of the abolishment of fluoroquinolone prophylaxis, as it is well known that chronic antibiosis induces a disruption of intestinal microbiota, which favours Clostridiodes infections (18)(19)(20). Overall, Clostridiodes are still involved in a high percentage of infections, also in Cohort B.…”

Section: Discussionmentioning

confidence: 99%

Results of an Innovative Program for Surveillance, Prophylaxis, and Treatment of Infectious Complications Following Allogeneic Stem Cell Transplantation in Hematological Malignancies (BATMO Protocol)

et al. 2022

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BackgroundInfectious complications are a significant cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-SCT). The BATMO (Best-Antimicrobial-Therapy-TMO) is an innovative program for infection prevention and management and has been used in our centre since 2019. The specific features of the BATMO protocol regard both prophylaxis during neutropenia (abandonment of fluoroquinolone, posaconazole use in high-risk patients, aerosolized liposomal amphotericin B use until engraftment or a need for antifungal treatment, and letermovir use in CMV-positive recipients from day 0 to day +100) and therapy (empirical antibiotics based on patient clinical history and colonization, new antibiotics used in second-line according to antibiogram with the exception of carbapenemase-producing K pneumoniae for which the use in first-line therapy is chosen).MethodsData on the infectious complications of 116 transplant patients before BATMO protocol (Cohort A; 2016 - 2018) were compared to those of 84 transplant patients following the introduction of the BATMO protocol (Cohort B; 2019 - 2021). The clinical and transplant characteristics of the 2 Cohorts were comparable, even though patients in Cohort B were at a higher risk of developing bacterial, fungal, and CMV infections, due to a significantly higher proportion of myeloablative regimens and haploidentical donors.ResultsNo change in the incidence of infections with organ localization was observed between the two Cohorts. A significant reduction in Clostridioides difficile infections by day +100 was observed in Cohort B (47% vs. 15%; p=0.04). At day +30, a higher incidence of Gram-negative bloodstream infections (BSIs) was observed in Cohort B (12% vs. 23%; p=0.05). By day +100 and between days +100 and +180, the incidence of BSIs and of the various etiological agents, the mortality from Gram-negative bacteria, and the incidence of invasive fungal infections were not different in the two Cohorts. The incidence of CMV reactivations by day +100 dropped drastically in patients of Cohort B, following letermovir registration (51% vs. 15%; p=0.00001).DiscussionThe results of this study suggest that the BATMO program is safe. In particular, the choice to avoid prophylaxis with fluoroquinolone was associated with an increase in Gram-negative BSIs by day +30, but this did not translate into higher levels of mortality. Moreover, this strategy was associated with a significant reduction of Clostridiodes difficile infections. The efficacy of anti-CMV prophylaxis with letermovir was confirmed by a significant reduction in CMV reactivations. Even though patients in Cohort B were at higher risk of developing fungal infections (more haploidentical transplants with more myeloablative regimens), the extensive use of posaconazole for prophylaxis balanced this risk, and no increase in the incidence of fungal-associated complications was observed.

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Section: Discussionmentioning

confidence: 99%

Results of an Innovative Program for Surveillance, Prophylaxis, and Treatment of Infectious Complications Following Allogeneic Stem Cell Transplantation in Hematological Malignancies (BATMO Protocol)

et al. 2022

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“…CDI has been increasingly discerned among HSCT recipients because of the fragility of the immune system, graft-versus-host disease (GVHD), and antibiotic usage or prophylaxis ( Ilett et al., 2019 ; Rosignoli et al., 2020 ; Jabr et al., 2021 ). Along with the growing cognition on CDI for clinical physicians and improving diagnostic capacity of laboratories on CDI, the relevant data on the prevalence of reported CDI have gradually increased in recent years.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis

Luo

Su-mei

Shang

et al. 2022

Front. Cell. Infect. Microbiol.

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Hematopoietic stem cell transplant (HSCT) recipients are vulnerable to Clostridium difficile infection (CDI) due to risk factors such as immunosuppression, antimicrobial use, and frequent hospitalization. We systematically searched PubMed and Embase to screen relevant studies from April 2014 to November 2021. A meta-analysis was performed to identify the association between CDI and hematopoietic transplantation based on the standard mean difference and 95% confidence intervals (CIs). Among the 431 retrieved citations, we obtained 43 eligible articles, which included 15,911 HSCT patients at risk. The overall estimated prevalence of CDI was 13.2%. The prevalence of CDI among the 10,685 allogeneic transplantation patients (15.3%) was significantly higher than that among the 3,840 autologous HSCT recipients (9.2%). Different incidence rates of CDI diagnosis over the last 7 years were found worldwide, of which North America (14.1%) was significantly higher than Europe (10.7%) but not significantly different from the prevalence among Asia (11.6%). Notably, we found that the estimated prevalence of CDI diagnosed by polymerase chain reaction (PCR) (17.7%) was significantly higher than that diagnosed by enzyme immunoassay (11.5%), indicating a significant discrepancy in the incidence rate of CDI owing to differences in the sensibility and specificity of the detection methods. Recurrence of CDI was found in approximately 15% of the initial patients with CDI. Furthermore, 20.3% of CDI cases were severe. CDI was found to be a common complication among HSCT recipients, displaying an evident increase in the morbidity of infection.

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“…The domination of enterococci in posttransplant stool specimens is positively related to the subsequent development of gastrointestinal GvHD, and the mean proportion of enterococci increased by 53% at the time of active GvHD [ 15 , 22 ]. Also, intestinal dysbiosis in HSCT patients is correlated with multiple infections including bloodstream infection [ 23 ], diarrhea [ 9 ], multidrug-resistant organism (MDRO) infection [ 24 ], and pulmonary infections [ 25 ]. Moreover, a retrospective observational analysis of 541 patients undergoing allo-HSCT identified that the intestinal microbiota could be associated with relapse/progression of disease after allo-HSCT [ 26 ].…”

Section: Intestinal Dysbiosis In Patients Undergoing Hsct: Adverse Ef...mentioning

confidence: 99%

“…Rapid shifts in the composition and function of intestinal microbial communities, known as intestinal dysbiosis, are associated with intestinal barrier disruption and lead to the development of inflammatory [ 5 ], cancer [ 6 ], metabolic diseases [ 7 ], and neurodegenerative diseases [ 8 ]. Patients undergoing HSCT display significant changes in the gut microbiota due to the underlying malignancy and exposures to extensive chemotherapy, immunosuppressants, and systemic antibiotics [ 9 ]. Due to the clinical significance of gut microbiota, significant interest has emerged to understand the interplay between gut microbiota and HSCT-related complications and reveal the therapeutic value of this interaction.…”

Section: Introductionmentioning

confidence: 99%

Role of Gut Microbiota and Oxidative Stress in the Progression of Transplant-Related Complications following Hematopoietic Stem Cell Transplantation

Chi

Jiang

et al. 2023

Oxidative Medicine and Cellular Longevity

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Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, has curative potential for various hematologic malignancies but is associated with risks such as graft-versus-host disease (GvHD), severe bloodstream infection, viral pneumonia, idiopathic pneumonia syndrome (IPS), lung fibrosis, and sinusoidal obstruction syndrome (SOS), which severely deteriorate clinical outcomes and limit the wide application of HSCT. Recent research has provided important insights into the effects of gut microbiota and oxidative stress (OS) on HSCT complications. Therefore, based on recent studies, we describe intestinal dysbiosis and OS in patients with HSCT and review recent molecular findings underlying the causal relationships of gut microbiota, OS, and transplant-related complications, focusing particularly on the involvement of gut microbiota-mediated OS in postengraftment complications. Also, we discuss the use of antioxidative and anti-inflammatory probiotics to manipulate gut microbiota and OS, which have been associated with promising effects in improving HSCT outcomes.

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Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Cited by 7 publications

References 38 publications

Results of an Innovative Program for Surveillance, Prophylaxis, and Treatment of Infectious Complications Following Allogeneic Stem Cell Transplantation in Hematological Malignancies (BATMO Protocol)

Results of an Innovative Program for Surveillance, Prophylaxis, and Treatment of Infectious Complications Following Allogeneic Stem Cell Transplantation in Hematological Malignancies (BATMO Protocol)

Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis

Role of Gut Microbiota and Oxidative Stress in the Progression of Transplant-Related Complications following Hematopoietic Stem Cell Transplantation

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