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Impact of Anti-anaerobic Antibiotic Activity on Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients at an Institution that Utilizes Antibiotic Cycling
Hanks, C. R., Slain, D., Kanate, A. S., Wen, S., Cumpston, A.
Transplant infectious disease : an official journal of the Transplantation Society. 2021;:e13676
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Abstract
BACKGROUND At our institution, antibiotic cycling for febrile neutropenia is utilized to increase heterogeneity of antibiotic exposure in patients who have undergone an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Development of acute graft-versus-host disease (aGVHD) has been associated with low diversity within stool microbiota. To date, discordant outcomes have been reported implicating anti-anaerobic antibiotic use with the development of aGVHD, and there is currently a lack of published data available in an antibiotic cycled environment. The objective of this study was to determine if there is a difference in the rate of aGVHD in patients who receive anti-anaerobic cycled antibiotics compared to other cycled antibiotics. METHODS This was a retrospective, observational study evaluating rates of aGVHD in patients who received antibiotics with anaerobic versus non-anaerobic coverage post-allo-HSCT from January 2008 to January 2018. Univariate and multivariable analyses were performed to assess associations with aGVHD. Secondary outcomes include rate of all stages of aGVHD, progression free survival (PFS), overall survival (OS), 100-day treatment-related mortality (TRM), and 1-year TRM. RESULTS A total of 273 patients were included in the study. Baseline characteristics were similar between groups, except patients who received anti-anaerobic antibiotics had more unrelated donors (p=0.002), were more likely to get myeloablative preparatory regimens (p=0.009), had less subtherapeutic calcineurin inhibitor serum concentrations (p=0.001), and more often received T-cell depletion (p=0.004). The incidence of grade II-IV aGVHD post-HSCT in patients who received anti-anaerobic antibiotics was 32.6% compared to 18.8% in patients who received other antibiotics (p=0.015). Multivariable analysis showed that the occurrence of grade II-IV aGVHD was associated with CMV reactivation (OR=2.1, 95% CI 1.0-4.5, p=0.047), unrelated donors (OR=6.1, 95% CI 2.3-16.6, p<0.001), and use of anti-anaerobic antibiotics (OR=2.3, 95% CI 1.1-4.8, p=0.021). 100-day TRM in patients who received anti-anaerobic antibiotics was 9.6% compared to 3.6% in patients who received other antibiotics (p=0.046). One-year TRM in patients who received anti-anaerobic antibiotics was 25.2% compared to 13.8% in patients who received other antibiotics (p=0.017). There was no statistically significant difference seen between groups in PFS or OS. CONCLUSION Variability in baseline characteristics limit ability to make strong conclusions, but patients who received antibiotics with anaerobic coverage during the first 30 days after an allogeneic HSCT appeared to be at an increased risk of developing aGVHD and TRM. Larger well-controlled trials are warranted to further clarify these relationships.
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Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients
Austin, K., Sweet, M., Likar, E., LaSala, P. R., Murray, A., Wen, S., Ross, K. G., Kanate, A. S., Veltri, L., Matuga, R., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2020;:e13438
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Abstract
BACKGROUND Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of C. difficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population. METHODS The primary objectives of this study were to identify the rate of C. difficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient. RESULTS Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of C. difficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles. CONCLUSIONS Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.
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Low-Dose Acyclovir Prophylaxis for Varicella zoster Reactivation in Autologous Hematopoietic Cell Transplantation Recipients
Fei, N., Shah, N., Cumpston, A., Wen, S., Ross, K. G., Craig, M., Kanate, A. S.
Clinical hematology international. 2019;1(2):101-104
Abstract
Varicella zoster virus (VZV) reactivation after autologous hematopoietic cell transplantation (auto-HCT) may be observed in a quarter of patients. Currently, prophylactic use of acyclovir 800 mg twice daily or valacyclovir 500 mg twice daily is recommended for prophylaxis against VZV reactivation for at least one-year post-HCT, with continued use recommended in immunosuppressed recipients. Acyclovir dosing regimens vary between institutions despite the noted recommendations. In this single-center, retrospective study, recipients of auto-HCT who received at least one year of low-dose antiviral prophylaxis defined as the equivalent of acyclovir 400 mg orally twice daily or valacyclovir 500 mg daily were included. The primary objective of this study was to assess the incidence of VZV reactivation with low-dose acyclovir/valacyclovir prophylaxis in autograft recipients. One hundred and eighty patients undergoing auto-HCT between April 2008 and March 2015 were included. Patients received low-dose acyclovir, for a median duration of 55.5 months (range 12-100). There were no occurrences of VZV reactivation while patients were on these drugs. However, 2 patients (1.1%) had VZV reactivation after discontinuation of therapy, occurring 18.8 and 14 months from transplant and 6.7 and 2 months after stopping prophylaxis, respectively. Our retrospective analysis found low-dose antiviral prophylaxis with oral acyclovir 400 mg twice daily or valacyclovir 500 mg daily to be effective in preventing VZV reactivation in auto-HCT recipients.