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.

backgroundAt 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 with other cycled antibiotics.

methodsThis was a retrospective, observational study evaluating rates of aGVHD in patients who received antibiotics with anaerobic vs 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, overall survival, 100-day treatment-related mortality (TRM), and 1-year TRM.

resultsA 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 = .002), were more likely to get myeloablative preparatory regimens (P = .009), had less subtherapeutic calcineurin inhibitor serum concentrations (P = .001), and more often received T-cell depletion (P = .004). The incidence of grades II-IV aGVHD post-HSCT in patients who received anti-anaerobic antibiotics was 32.6% compared with 18.8% in patients who received other antibiotics (P = .015). Multivariable analysis showed that the occurrence of grades II-IV aGVHD was associated with cytomegalovirus reactivation (OR = 2.1, 95% CI = 1.0-4.5, P = .047), unrelated donors (OR = 6.1, 95% CI = 2.3-16.6, P < .001), and use of anti-anaerobic antibiotics (OR = 2.3, 95% CI = 1.1-4.8, P = .021). A 100-day TRM in patients who received anti-anaerobic antibiotics was 9.6% compared with 3.6% in patients who received other antibiotics (P = .046). One-year TRM in patients who received anti-anaerobic antibiotics was 25.2% compared with 13.8% in patients who received other antibiotics (P = .017). There was no statistically significant difference seen between groups in progression free survival or overall survival.

conclusionVariability in baseline characteristics limits 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.