1.
Impact of carbapenem antibiotics on mycophenolate mofetil in hematopoietic stem cell transplant patients with interruption of the enterohepatic recycling: a retrospective study
Tian, J. X., Miao, W. J., Yan, H. H., Wang, X. D., Liao, Y. X., Li, S., Jiang, E. L., Zhang, P.
Annals of translational medicine. 2023;11(2):82
Abstract
BACKGROUND Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is widely used in the prophylaxis for graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). MPA undergoes enterohepatic recycling (EHR). Oral antibiotics can affect MPA concentration by reducing intestinal flora-mediated EHR. However, the effect of intravenous antibiotics on MPA concentration is not clear, especially in patients whose EHR is already interrupted. This study was conducted to determine whether intravenous carbapenem antibiotics (CBP) influence the pre-dose plasma concentration (C(0)) of MPA in HSCT patients when the EHR of MPA is interrupted by cyclosporine and gut decontamination. METHODS The HSCT patients who received immunosuppressive therapy with MMF and cyclosporine, as well as treatment with CBP were screened as potential candidates. Patients who lacked MPA C(0) measurements before or during CBP use, had combination therapy of rifampin with MMF, or switched from IV to oral MMF were excluded. The liver/renal function, demographic information, albumin/cyclosporine concentration, MPA C(0) and medication information were collected. The changes in the MPA C(0) before and during CBP use were evaluated, and the influence of related clinical factors was also estimated. RESULTS CBP resulted in a significant reduction in the MPA C(0) from 0.65±0.33 to 0.43±0.30 µg/mL. Linear regression analysis indicated a weak correlation between the dose-normalized C(0) of MPA and the dosage of CBP during CBP use (r(2)=0.129, P=0.009). Univariate and multivariate analysis confirmed that the MPA C(0) had no relevance to rifaximin administration (P=0.249-0.700), demographics (P=0.118-0.599), fluctuation of plasma albumin (ALB, P=0.943 and 0.609) and cyclosporine concentrations (P=0.647 and 0.112), or liver and renal functions (P=0.078-0.887) no matter whether the CBP were used. However, compared with the non-gut decontamination group, larger interindividual variabilities and smaller decreases in MPA C(0) (6.60% vs. 41.73%) during CBP therapy were seen in the gut decontamination group, although it was a nonsignificant trend. CONCLUSIONS CBP decreased the MPA C(0) in Chinese HSCT patients even when MMF is used in combination with cyclosporine and rifaximin. If antibiotics must be used, and CBP in particular, therapeutic drug monitoring should be performed to ensure adequate exposure.
2.
Post-transplantation cyclophosphamide is associated with increased bacterial infections
Ustun, C., Chen, M., Kim, S., Auletta, J. J., Batista, M. V., Battiwalla, M., Cerny, J., Gowda, L., Hill, J. A., Liu, H., et al
Bone marrow transplantation. 2023
Abstract
Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis [Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605] were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 [HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001]. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality [HaploCy (HR1.84, 99% CI: 1.45-2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30-2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43-2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.
3.
Bacterial Bloodstream Infections in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide
Salas, M. Q., Charry, P., Alcalde, P. P., Cibrian, N. M., Solano, M. T., Serrahima, A., Nomdedeu, M., Cid, J., Lozano, M., Chumbinta, M., et al
Transplantation and cellular therapy. 2022
Abstract
This study investigates the incidence and predictors for bacterial bloodstream infection (BSI) in 330 adults undergoing allo-HCT, and explores the effect of PTCY on the probability of presenting this complication. All patients received levofloxacin during the aplastic phase. Only the first episode of BSI was accounted as an event. Patients were classified into two groups: PTCY-based (n=200) vs. other prophylaxis (n=130). 124 patients were diagnosed with a first episode of BSI, most of them during the first 30 days (70.2%). Proportions of BSIs caused by Gram-positive bacteria were comparable to those caused by Gram-negative bacteria (48.3% vs. 45.9%). The cumulative incidence of BSI was higher in patients receiving PTCY than in those receiving other prophylaxis (Day +30 and +100: 35.0% and 37.0% vs. 13.1% and 18.5%, P<0.001). At day +30, the likelihood of BSI was 2.41 (P=0.012) times higher in the PTCY's than in the non-PTCY's group. The day 30 mortality rate in all patients with BSI was 8.0%, lower (P=0.002) in the PTCY's group (2.3%) than in the non-PTCY's one (21.6%). Finally, the overall survival of patients receiving PTCY and diagnosed with BSI was similar to that of patients without presenting this complication.