Impact of the Use and Type of Antibiotics on Acute Graft-versus-Host Disease
Impact of the Use and Type of Antibiotics on Acute Graft-versus-Host Disease
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DOI：
10.1016/j.bbmt.2018.06.031
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发表时间：
2018-11-01
影响因子：
4.3
通讯作者：
Takaori-Kondo, Akifumi
中科院分区：
文献类型：
--
作者：
Nishi, Katsuyuki;Kanda, Junya;Takaori-Kondo, Akifumi
肠道菌群在急性移植物抗宿主病（aGVHD）的发病机制中起重要作用。在造血干细胞移植（HSCT）过程中，肠道菌群受到广谱抗生素使用的影响。然而，抗生素的使用和类型对微生物群组成的影响以及随后aGVHD的发生仍然知之甚少。我们假设抗生素的使用和类型对aGVHD的发生有影响。我们评估了2005年1月至2015年6月期间在京都大学医院接受首次同种异体HSCT的275例患者。我们监测了6种最常使用的抗生素（第四代头孢菌素类、糖肽类、哌拉西林-他唑巴坦类、碳青霉烯类、氨基糖苷类和喹诺酮类），这些抗生素在HSCT的-14天和+14天之间使用，以及HSCT的持续时间。主要终点是II至IV级aGVHD的累积发生率。使用第四代头孢菌素的患者aGVHD的累积发生率显著高于未使用第四代头孢菌素的患者（II至IV级：风险比，1.98; 95%置信区间，1.19至3.29; P= 0.0087; III至IV级：风险比，8.03; 95%置信区间，1.07至60.51; P=.043）。与此相反，其他抗生素的使用与aGVHD的发生率之间无显著相关性。至于器官特异性aGVHD，肠道aGVHD的累积发生率在接受第四代头孢菌素的患者中显著高于未接受第四代头孢菌素的患者（31%对16%，P = 0.018）。总之，我们证明了第四代头孢菌素的管理对aGVHD的发展有很大的影响。(C)2018年美国血液和骨髓移植协会。
The intestinal microbiota plays an important role in the pathogenesis of acute graft-versus-host disease (aGVHD). During the course of hematopoietic stem cell transplantation (HSCT), the intestinal microbiota is influenced by the use of broad-spectrum antibiotics. However, the impact of the use and type of antibiotics on the microbiota composition and, subsequently, the onset of aGVHD remain poorly understood. We hypothesized that the use and type of antibiotics had an impact on the occurrence of aGVHD. We assessed 275 patients who underwent their first allogeneic HSCT between January 2005 and June 2015 at Kyoto University Hospital. We monitored the 6 most frequently administered antibiotics (fourth-generation cephalosporins, glycopeptides, piperacillin-tazobactam, carbapenems, aminoglycosides, and quinolones) administered between days -14 and +14 relative to HSCT and its duration. The primary endpoint was the cumulative incidence of grades II to IV aGVHD. The cumulative incidence of aGVHD was significantly higher in patients administered fourth-generation cephalosporins than in patients not receiving fourth-generation cephalosporins (grades II to IV: hazard ratio, 1.98; 95% confidence interval, 1.19 to 3.29; P=.0087; grades III to IV: hazard ratio, 8.03; 95% confidence interval, 1.07 to 60.51; P=.043). In contrast, there was no significant association between administration of other antibiotics and aGVHD incidence. As for organ-specific aGVHD, the cumulative incidence of gut aGVHD was significantly higher in patients who received fourth-generation cephalosporins than in those who did not (31% versus 16%, P =.018). In conclusion, we demonstrated that the administration of fourth-generation cephalosporins had a strong impact on the development of aGVHD. (C) 2018 American Society for Blood and Marrow Transplantation.