Fred Hutchinson Cancer Center, Seattle, Washington.
Division of Medical Oncology, Department of Medicine, University of Washington.
JAMA Netw Open. 2023 Jun 1;6(6):e2317188. doi: 10.1001/jamanetworkopen.2023.17188.
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.
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.
Antibiotics between 7 days before and 30 days after transplant.
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.
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).
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.
某些抗生素的暴露与异基因造血细胞移植（allo-HCT）后急性移植物抗宿主病（aGVHD）的发生率增加有关。由于抗生素的暴露既可以影响感染，也可以被感染所影响，因此在存在多个潜在混杂因素的情况下，分析时间依赖性暴露，包括先前的抗生素暴露，具有特定的分析挑战，这需要大样本量和独特的方法。
确定与随后的 aGVHD 相关的抗生素和抗生素暴露时间范围。
设计、设置和参与者：这项队列研究评估了 2010 年至 2021 年在一个中心进行的 allo-HCT。参与者包括至少 18 岁接受首次 T 细胞完全 allo-HCT 且至少有 6 个月随访的所有患者。数据于 2022 年 8 月 1 日至 12 月 15 日进行分析。
移植前 7 天至移植后 30 天的抗生素。
主要结局是 2 级至 4 级 aGVHD。次要结局是 3 级至 4 级 aGVHD。数据使用 3 种正交方法进行分析：传统的 Cox 比例风险回归、边缘结构模型和机器学习。
共有 2023 名患者（中位[范围]年龄，55[18-78]岁；1153[57%]为男性）符合条件。HCT 后第 1 周和第 2 周是风险最高的时间段，多种抗生素暴露与随后发生 aGVHD 的风险增加有关。特别是，allo-HCT 后第 1 周和第 2 周接受碳青霉烯类抗生素暴露与 aGVHD 风险增加一致（模型中最小的危害比[HR]，2.75；95%CI，1.77-4.28），allo-HCT 后第 1 周接受青霉素与β-内酰胺酶抑制剂联合用药的暴露也有相同的结果（模型中最小的 HR，6.55；95%CI，2.35-18.20）。
在这项 allo-HCT 受者的队列研究中，移植早期的抗生素选择和方案与 aGVHD 发生率有关。在抗生素管理计划中应考虑到这些发现。
