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1.
The clinical value of anal swabs for microbial detection in allogeneic haematopoietic stem cell transplantation
Gao, J., Lin, D., Hou, C., Shen, Y., Li, Y., Wu, D., Xu, Y.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The intestinal microbiota plays critical roles in allogeneic haematopoietic stem cell transplantation (allo-HSCT). Rapid and effective microbial detection methods have important guiding value for the selection of intervention strategies for transplant patients. We evaluate the application of anal swab test before transplantation in allo-HSCT patients. STUDY DESIGN A total of 120 allo-HSCT patients who underwent anal swab testing before allo-HSCT were retrospectively analysed and divided into sterile (aseptic growth-negative), G+ (gram-positive bacterial colonization) and G- (gram-negative bacterial colonization) groups. RESULTS 16S rRNA sequencing showed that gram-negative bacteria predominated in the G- group before and after transplantation. Compared with the sterile group, NK cell percentage was higher and T cell percentage was lower after transplantation in the G- group at one month after transplantation. The percentage of CD4+T and CD4+CD8+ T cells was lower, and the percentage of Treg was higher in the G- group. The plasma levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6, and IL-17A) were lower in the G- group at 2 weeks after transplantation than in the sterile group. The cumulative incidence of grade III-IV aGVHD was lower in the G- group than in the sterile group. Gram-negative bacterial colonization before allo-HSCT was associated with low rates of BSI within 100 days posttransplatation, and CMV reactivation after 100 days to 2 years posttransplatation. Moreover, patients in the G- group had a higher rate of 2-year GRFS compared with patients in the sterile group. CONCLUSIONS The detection results using anal swabs were consistent with the gram-negative or positive bacteria abundance of 16S rRNA sequencing results and associated with immune homeostasis and clinical outcomes after allo-HSCT. Anal swab testing may have potential advantages as a simple and effective method for microbial detection in allo-HSCT.
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2.
Risk factors and outcome of Stenotrophomonas maltophilia infection after allogeneic hematopoietic stem cell transplantation: JSTCT, Transplant Complications Working Group
Saburi, M., Oshima, K., Takano, K., Inoue, Y., Harada, K., Uchida, N., Fukuda, T., Doki, N., Ikegame, K., Matsuo, Y., et al
Annals of hematology. 2023
Abstract
Stenotrophomonas maltophilia (S. maltophilia) is an aerobic nonfermenting Gram-negative bacillus widely distributed in the environment that has inherent multidrug resistance to beta-lactam and carbapenem antibiotics. S. maltophilia infection (SMI) is known as an important fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its clinical characteristics have not been well clarified. A retrospective study to identify the incidence, risk factors, and outcomes of SMI after allogeneic HSCT was performed using the database of the Japanese nationwide registry, including 29,052 patients who received allogeneic HSCT in Japan between January 2007 and December 2016. A total of 665 patients developed SMI (sepsis/septic shock, 432; pneumonia, 171; other, 62). The cumulative incidence of SMI at 100 days after HSCT was 2.2%. Among risk factors identified for SMI (age ≥ 50 years, male, performance status 2-4, cord blood transplantation [CBT], myeloablative conditioning, Hematopoietic Cell Transplant-Comorbidity Index [HCT-CI] score 1-2, HCT-CI score ≥ 3, and active infectious disease at HSCT), CBT was the strongest risk factor (hazard ratio, 2.89; 95%CI, 1.94-4.32; p < 0.001). The survival rate at day 30 after SMI was 45.7%, and SMI before neutrophil engraftment was significantly associated with poor survival (survival rate 30 days after SMI, 40.1% and 53.8% in patients with SMI before and after engraftment, respectively; p = 0.002). SMI is rare after allogeneic HSCT, but its prognosis is extremely poor. CBT was a strong risk factor for SMI, and its development prior to neutrophil engraftment was associated with poor survival.
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3.
Drug-monitoring during ciprofloxacin prophylaxis of allogeneic stem cell transplant patients - associations with bacterial infections through a monocentric observational prospective study
Kaba, H. E. J., Hasenkamp, J., Tas, H., Schulz, M., Streit, F., Eiffert, H., Wulf, G., Truemper, L., Binder, L., Kaase, M., et al
The Journal of hospital infection. 2023
Abstract
Bacterial infection ranks amongst the most frequent causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem-cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking. Thus, we aimed at investigating relationships between CIP-levels and prophylaxis-failure; especially whether different pharmacokinetic (PK)-indices (AUC(0-24h) vs. single time samples) correlate differently with the outcome. We conducted a prospective observational monocentric study at a 1,500-bed teaching hospital (2018/03/18-2019/03/19), including 63 adult alloHSCT-patients receiving CIP-prophylaxis. Blood samples were drawn at three sampling-times (1h, 6h and 12h post administration), twice-a-week, and measured via HPLC. Onset of febrile episodes (FEB) indicated suspected ciprofloxacin prophylaxis failure. Events of positive blood-cultures (bloodstream infection; BSI) indicated confirmed prophylaxis-failure. Seven out of 63 patients died without significant differences in their average CIP-levels compared to survivors, with FEB-patients (54/63) displaying a 13%, 95% CI: 4 - 22% lower probability to survive. We obtained 225 triplets from 58 primary CIP-episodes. Triplets preceding BSI with gram-negative bacteria (GNB-BSI) showed lower AUC(0-24h) on average, but indifferent single time sample indices. An AUC(0-24h) of ≤ 21.61 mgh/L resulted in 4-fold higher odds of GNB-BSI (OR(adj) = 3.96, 95% CI: 1.21 - 13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indicating reduced CIP-exposure upon GNB-BSI events. CIP-level monitoring, using multiple sampling-times, might thus be useful to reduce alloHSCT-associated bacterial infections, while further analysis is needed to investigate causality.
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4.
Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
Rashidi, A., Gao, F., Fredricks, D. N., Pergam, S. A., Mielcarek, M., Milano, F., Sandmaier, B. M., Lee, S. J.
JAMA network open. 2023;6(6):e2317188
Abstract
IMPORTANCE Certain antibiotic exposures have been associated with increased rates of acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Since antibiotic exposure can both affect and be affected by infections, analyzing time-dependent exposure in the presence of multiple potential confounders, including prior antibiotic exposures, poses specific analytical challenges, necessitating both a large sample size and unique approaches. OBJECTIVE To identify antibiotics and antibiotic exposure timeframes associated with subsequent aGVHD. DESIGN, SETTING, AND PARTICIPANTS This cohort study assessed allo-HCT at a single center from 2010 to 2021. Participants included all patients aged at least 18 years who underwent their first T-replete allo-HCT, with at least 6 months of follow-up. Data were analyzed from August 1 to December 15, 2022. EXPOSURES Antibiotics between 7 days before and 30 days after transplant. MAIN OUTCOMES AND MEASURES The primary outcome was grade II to IV aGVHD. The secondary outcome was grade III to IV aGVHD. Data were analyzed using 3 orthogonal methods: conventional Cox proportional hazard regression, marginal structural models, and machine learning. RESULTS A total of 2023 patients (median [range] age, 55 [18-78] years; 1153 [57%] male) were eligible. Weeks 1 and 2 after HCT were the highest-risk intervals, with multiple antibiotic exposures associated with higher rates of subsequent aGVHD. In particular, exposure to carbapenems during weeks 1 and 2 after allo-HCT was consistently associated with increased risk of aGVHD (minimum hazard ratio [HR] among models, 2.75; 95% CI, 1.77-4.28), as was week 1 after allo-HCT exposure to combinations of penicillins with a β-lactamase inhibitor (minimum HR among models, 6.55; 95% CI, 2.35-18.20). CONCLUSIONS AND RELEVANCE In this cohort study of allo-HCT recipients, antibiotic choices and schedules in the early course of transplantation were associated with aGVHD rates. These findings should be considered in antibiotic stewardship programs.
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5.
Epidemiology, outcomes and risk factors for recurrence of Clostridioides difficile infections following allogeneic hematopoietic cell transplantation: a longitudinal retrospective multicenter study
Ragozzino, S., Mueller, N. J., Neofytos, D., Passweg, J., Müller, A., Medinger, M., Van Delden, C., Masouridi-Levrat, S., Chalandon, Y., Tschudin-Sutter, S., et al
Bone marrow transplantation. 2023
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6.
Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses
Vallet, N., Salmona, M., Malet-Villemagne, J., Bredel, M., Bondeelle, L., Tournier, S., Mercier-Delarue, S., Cassonnet, S., Ingram, B., Peffault de Latour, R., et al
Cell host & microbe. 2023
Abstract
Early administration of azithromycin after allogeneic hematopoietic stem cell transplantation was shown to increase the relapse of hematological malignancies. To determine the impact of azithromycin on the post-transplant gut ecosystem and its influence on relapse, we characterized overtime gut bacteriome, virome, and metabolome of 55 patients treated with azithromycin or a placebo. We describe four enterotypes and the network of associated bacteriophage species and metabolic pathways. One enterotype associates with sustained remission. One taxon from Bacteroides specifically associates with relapse, while two from Bacteroides and Prevotella correlate with complete remission. These taxa are associated with lipid, pentose, and branched-chain amino acid metabolic pathways and several bacteriophage species. Enterotypes and taxa associate with exhausted T cells and the functional status of circulating immune cells. These results illustrate how an antibiotic influences a complex network of gut bacteria, viruses, and metabolites and may promote cancer relapse through modifications of immune cells.
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7.
Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study
Gill, J., Busca, A., Cinatti, N., Passera, R., Dellacasa, C. M., Giaccone, L., Dogliotti, I., Manetta, S., Corcione, S., De Rosa, F. G.
Microorganisms. 2023;11(3)
Abstract
Background-Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are subject to major risks for bacterial bloodstream infections (BSIs), including emergent multidrug-resistant (MDR) organisms, which still represent the main cause of morbidity and mortality in transplanted patients. METHODS We performed an observational, retrospective, single-center study on patients undergoing allo-HSCT between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of BSIs and to explore any risk factors for bacteriaemia. RESULTS We observed a total of 178 bacterial BSIs in our cohort of 563 patients, resulting in a cumulative incidence of 19.4%, 23.8%, and 28.7% at 30, 100, and 365 days, respectively. Among isolated bacteria, 50.6% were Gram positive (GPB), 41.6% were Gram negative (GNB), and 7.9% were polymicrobial infections. Moreover, BSI occurrence significantly influenced 1-year overall survival. High and very high Disease Risk Index (DRI), an haploidentical donor, and antibacterial prophylaxis were found as results as independent risk factors for bacterial BSI occurrence in multivariate analysis. CONCLUSIONS In our experience, GNB have overwhelmed GPB, and fluoroquinolone prophylaxis has contributed to the emergence of MDR pathogens. Local resistance patterns and patients' characteristics should therefore be considered for better management of bacteremia in patients receiving an allogeneic HSCT.
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8.
Epidemiology, drug resistance analysis and mortality risk factor prediction of gram-negative bacteria infections in patients with allogeneic hematopoietic stem cell transplantation
Liu, Y., Liu, Y., Liu, Y., Chen, X., Jia, Y.
Heliyon. 2023;9(4):e15285
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for many malignant and refractory diseases. However, infections, as the most common complication after transplantation, often lead to poor long-term prognosis of patients. In this study, we collected electronic medical records of allo-HSCT recipients with gram-negative bacteria (GNB) infections between January 2012 and September 2021, analyzed epidemiological characteristics and antibiotic sensitivity, and determined independent risk factors for carbapenem-resistant GNB (CR-GNB) infections and death by Logistic and Cox regression models. During the 9-year period, 183 of 968 patients developed GNB infections, of which 58 died. The most common pathogen was Klebsiella pneumoniae. CR-GNB, especially carbapenem-resistant Klebsiella pneumonia (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Escherichia coli (CREC) had a high resistance rate to commonly used clinical antibiotics. Independent risk factors for CR-GNB infections were use of carbapenem antibiotics for >3 days one month before transplantation (OR = 3.244, 95% CI 1.428-7.369, P = 0.005), use of special immunosuppressants after transplantation (OR = 1.21, 95% CI 1.008-1.452, P = 0.041), and time of hematopoietic reconstruction >20 days (OR = 2.628, 95% CI 1.369-5.043, P = 0.004). Independent risk factors for mortality were interval between diagnosis and transplantation >180 days (HR = 2.039, 95% CI 1.05 to 3.963, P = 0.035), total bilirubin levels during infection >34.2 μmol/L (HR = 3.39, 95% CI 1.583-7.256, P = 0.002) and septic shock (HR = 5.345, 95% CI 2.655-10.761, P = 0.000). In conclusion, GNB has a high incidence and mortality in allo-HSCT recipients. Early transplantation for eligible patients, attention to liver function protection, timely identification and treatment of septic shock can help to improve the prognosis of patients.
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9.
A low thrombospondin-1 serum concentration is related to increased bacteremia risk in lymphoma patients treated with BeEAM/BEAM conditioning regimen and autologous stem cell transplantation
Kościelny, K., Mikulski, D., Nowicki, M., Wyka, K., Misiewicz, M., Perdas, E., Wierzbowska, A., Fendler, W.
Transplant infectious disease : an official journal of the Transplantation Society. 2023;:e14212
Abstract
Infectious complications of autologous hematopoietic stem cell transplantation (AHSCT) are the most common adverse effects of the therapy, resulting in prolonged hospitalization and deterioration of patient well-being. Identifying predictors of these complications is essential for improving patient outcomes and guiding clinical management. This study aimed to examine thrombospondin-1 (THBS-1) serum levels as a potential biomarker for predicting bacteremia in AHSCT recipients. Blood samples were collected from 30 patients undergoing BeEAM/BEAM (bendamustine/carmustine, etoposide, cytarabine, melphalan) conditioning regimen at subsequent time points during AHSCT. THBS-1 levels were quantified using ELISA kits. Patients who developed bacteremia (n = 11) during the AHSCT course had lower THBS-1 concentration compared with those without (n = 19) (22.88 ± 11.53 µg/mL vs. 15.24 ± 5.62 µg/mL, p = .0325). The ROC curve analysis revealed that THBS-1 serum concentration at the first day of BeEAM/BEAM regimen had an area under the curve of 0.732 (95%CI: 0.5390.925, p = .0186) with an optimal cut-off value of 16.5 µg/ml resulting in 82% Sensitivity and 53% Specificity for predicting bacteremia with a median of 11 days before its occurrence. Patients with lower THBS-1 concentrations experienced febrile neutropenia significantly earlier, with a median difference of 5 days (p = .0037). Patients with a low concentration of THBS-1 had a higher risk of bacteremia and a shorter time to febrile neutropenia, indicating its potential value as a complications biomarker. Patients with lower serum THBS-1 concentrations, indicating an increased risk, may be more suitable for an inpatient AHSCT procedure, where close monitoring and immediate intervention are accessible.
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10.
Incidence, Etiology, Risk Factors, and Outcomes of Bloodstream Infection after a Second Hematopoietic Stem Cell Transplantation
Ohta, T., Ueno, T., Uehara, Y., Yokoyama, T., Nakazawa, M., Sato, Y., Uchida, Y., Ohno, Y., Sugio, Y.
Internal medicine (Tokyo, Japan). 2023
Abstract
Objective Infections after a second hematopoietic stem cell transplantation (HSCT) occur commonly and are associated with high mortality. However, studies on bloodstream infection (BSI) after a second HSCT are lacking. We therefore evaluated the details of BSI after a second HSCT. Methods We retrospectively evaluated the incidence, etiology, risk factors, and outcomes of BSI after a second HSCT. Patients Fifty-two adult patients with hematological malignancies who underwent allogeneic HSCT, including cord blood transplantation (CBT; n=33), as the second transplantation were enrolled. The second transplantation was limited to allogeneic HSCT. Patients who underwent HSCT for graft failure were excluded. Results The median HSCT interval was 438 (range: 39-3893) days. Overall, 31 (59.6%) patients received autologous HSCT as the first HSCT. The cumulative incidence of BSI was 40.4% at 100 days after the second HSCT, with Gram-positive bacteria accounting for the majority (30.8%) of pathogens. Overall, 92.0% of BSIs occurred during the pre-engraftment period, and Enterococcus faecium accounted for 29.6% of pathogens. On a multivariate analysis, CBT was most closely associated with pre-engraftment BSI after the second HSCT (hazard ratio: 3.43, 95% confidence interval: 1.05-11.23, P=0.042). The 1-year survival rate after the second HSCT was lower in patients with BSI than in patients without BSI (P=0.10). Conclusion BSI is common after a second HSCT, especially with CBT. During the pre-engraftment period, BSI caused by pathogens such as E. faecium should be anticipated and appropriately treated to improve transplant outcomes.