Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation.
Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation.
复制标题
DOI：
10.1001/jamanetworkopen.2023.17188
复制
发表时间：
2023-06-01
影响因子：
13.8
通讯作者：
Lee, Stephanie J.
中科院分区：
文献类型：
--
作者：
Rashidi, Armin;Gao, Fei;Fredricks, David N.;Pergam, Steven A.;Mielcarek, Marco;Milano, Filippo;Sandmaier, Brenda M.;Lee, Stephanie J.
异基因造血细胞移植(allo-HCT)后急性移植物抗宿主病(AGVHD)是否与抗生素和抗生素暴露时间相关？在这项包括2023名患者的队列研究中，采用3种正交法在allo-HCT手术前7天至术后30天期间使用抗生素，发现几种抗生素和暴露时间段与aGVHD发生率有关。最值得注意的是，碳青霉烯类和青霉素类药物与β-内酰胺酶抑制剂在异基因移植后前两周的使用一致地与aGVHD的风险增加有关。这些发现表明，在allo-HCT期间的抗生素管理计划中应考虑aGVHD风险。这项队列研究使用3种建模方法来确定抗生素和抗生素暴露时间范围与异基因造血细胞移植后急性移植物抗宿主病的风险相关。某些抗生素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。由于抗生素暴露既可以影响感染，也可以受到感染的影响，在存在多个潜在混杂因素的情况下分析依赖时间的暴露，包括先前的抗生素暴露，提出了具体的分析挑战，需要大量样本和独特的方法。确定与随后的aGVHD相关的抗生素和抗生素暴露时间范围。这项队列研究评估了从2010年到2021年在一个中心进行的allo-HCT。参与者包括所有年龄至少18岁的患者，他们接受了第一次T全异基因HCT，并进行了至少6个月的随访。对2022年8月1日至12月15日的数据进行了分析。移植前7天至移植后30天使用抗生素。主要结果为aGVHD II~IV级。次要结果为aGVHD III~IV级。使用3种正交法对数据进行分析：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(年龄中位数55[18-78]岁；男性1153[57%])符合条件。HCT后第1周和第2周是风险最高的时段，多次接触抗生素与随后aGVHD的较高发生率相关。特别是，在异体红细胞移植后1周和2周暴露于碳青霉烯类药物与aGVHD的风险增加一致相关(模型中的最小危险比[HR]，2.75；95%可信区间，1.77-4.28)，就像在异基因红细胞移植暴露于青霉素和β-内酰胺酶抑制剂的组合后的第一周一样(模型中的最低危险比，6.55；95%可信区间，2.35-18.20)。在这项针对allo-HCT接受者的队列研究中，移植早期的抗生素选择和时间表与aGVHD发生率相关。这些发现应该在抗生素管理计划中得到考虑。
Are antibiotics and antibiotic exposure timeframes associated with acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT)? In this cohort study including 2023 patients and using 3 orthogonal approaches applied to antibiotic use between 7 days before and 30 days after allo-HCT procedures, several antibiotics and exposure timeframes were found to be associated with aGVHD rates. Most notably, carbapenems and penicillins with a β-lactamase inhibitor used during the first 2 weeks after allo-HCT were consistently associated with increased hazard of aGVHD. These findings suggest that aGVHD risk should be considered in antibiotic stewardship programs during allo-HCT. This cohort study uses 3 modeling methods to identify antibiotics and antibiotic exposure timeframes associated with hazard of acute graft-vs-host disease after allogenic hematopoietic cell transplantation. 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. 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.
登录
查看更多内容
影响因子：
4.3
作者：
Bacigalupo, Andrea;Ballen, Karen;Rizzo, Doug;Giralt, Sergio;Lazarus, Hillard;Ho, Vincent;Apperley, Jane;Slavin, Shimon;Pasquini, Marcelo;Sandmaier, Brenda M.;Barrett, John;Blaise, Didier;Lowski, Robert;Horowitz, Mary
通讯作者：
Horowitz, Mary
DOI：
10.1084/jem.20112408
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jenq RR;Ubeda C;Taur Y;Menezes CC;Khanin R;Dudakov JA;Liu C;West ML;Singer NV;Equinda MJ;Gobourne A;Lipuma L;Young LF;Smith OM;Ghosh A;Hanash AM;Goldberg JD;Aoyama K;Blazar BR;Pamer EG;van den Brink MR
通讯作者：
van den Brink MR
影响因子：
20.3
作者：
Burgos da Silva, Marina;Ponce, Doris M;van den Brink, Marcel R M
通讯作者：
van den Brink, Marcel R M
影响因子：
56.3
作者：
Kokai-Kun, John F.;Roberts, Tracey;Sliman, Joseph
通讯作者：
Sliman, Joseph
影响因子：
20.3
作者：
Beelen, DW;Elmaagacli, A;Schaefer, UW
通讯作者：
Schaefer, UW