摘要
目的:感染有可能是自身免疫性疾病患者造血干细胞移植过程中的主要并发症,选择此类患者42例分析其临床感染特点与高危因素。方法:①实验对象:选取1999-01/2006-06郑州市第三人民医院收治的接受自体造血干细胞移植的重症自身免疫性疾病患者42例,移植前平均病程3年。实验经医院医学伦理委员会批准,患者均签署知情同意书。②实验方法:环磷酰胺150mg/kg+抗人胸腺球蛋白/抗人淋巴细胞球蛋白预处理30例,环磷酰胺200mg/kg+抗人胸腺球蛋白/抗人淋巴细胞球蛋白预处理12例;CD34+细胞纯化移植17例,CD34+细胞未纯化移植25例。移植过程中无菌层流室全环境保护,当患者体温>38℃时立即采集血液标本,15min/次,连续3次。同时依据感染部位,采集相应的分泌物标本,鉴定菌种,并进行药敏试验。移植后1～3个月出现发热的患者,应用酶免疫染色技术与ELISA法检测巨细胞病毒。结果:①感染病例临床特征:42例患者共32例于移植后发生感染,其中9例发生两个部位感染,4例发生3个部位感染。感染部位主要分布在口腔、肛周、肺部等,以及原发感染灶不明确的菌血症。细菌、真菌感染多发生在移植后1个月内,巨细胞病毒检测阳性多发生在移植后1～2.5个月,巨细胞病毒感染所致间质性肺炎多发生在移植后1～6个月。②病原菌分布与耐药:自身免疫性疾病自体造血干细胞移植后,真菌感染占36%,革兰氏阴性杆菌占32%,革兰氏阳性球菌占4%。实验所检出革兰氏阴性杆菌耐药率高,其中铜绿假单胞菌除对亚胺培南、头孢他啶、阿米卡星敏感外,对其他药物均耐药;大肠埃希氏菌对喹诺酮类、第3代头孢菌素等多种药物耐药,仅对氨基糖苷类敏感。③移植相关因素与感染发生:接受自体造血干细胞移植的自身免疫性疾病患者,其病程≥3年、移植前环磷酰胺用量≥5g、预处理环磷酰胺强度200mg/kg及CD34+细胞纯化的患者发生重度感染概率更高(χ2=4.783～8.776,P均<0.05)。结论:①自身免疫性疾病患者自体造血干细胞移植后,感染病原体以革兰氏阴性杆菌、真菌、巨细胞病毒为主,感染部位主要分布在口腔、肛周、肺部,细菌耐药率高。②感染发生除与原发病有关外,患者病程、移植前环磷酰胺用量、预处理方案及移植方式为显著相关危险因素。
AIM： Infection can be the main complication of autologous hematopoietic stem call transplantation （AHSCT） in patients with autoimmune disease. This article was designed to analyze the clinical infective characters and high risk factor in 42 patients. METHODS： ①Totally 42 patients with severe autoimmune disease treated by AHSCT from the Zhengzhou Third People＇s Hospital from January 1999 to June 2006. The average disease course was 3 years before transplantation. This test had been approved by the medical ethnics committee of the hospital, and all patients signed the informed consent. ②There were 30 cases of the pretreatment of Cyclophosphamide 150 mg/kg and Anti-human T-lymphocyte immunoglobulin/Anti-human lymphocyte globulin, 12 cases of the pretreatment of Cyclophosphamide 200 mg/kg and Anti-human T-lymphocyte immunoglobulin/Anti-human lymphocyte globulin. There were 17 cases of CD34^＋ cell autologous transplantation, and 25 cases of non-selected CD34^＋ cell autologous transplantation. The patients were protected in aseptic laminar flow room during the transplantatio9, when the temperature was over 38℃, the blood samples were collected instantly, 15 minutes per times, consecutively 3 times. Meanwhile, according to the infection locus, corresponding secretion samples were collected to identify strain, and then drug sensitive test was performed. The patients with fever were determined by enzyme-linked immunoadsordent assay （ELISA） to test cytomegalovirus after transplantation within 3 months. RESULTS：①Clinical character of the infected case： The 32 cases of 42 were infected after transplantation. There were two infected parts in 9 cases, three infected parts in 4 cases. The infected Iocuses were mainly seen in oral cavity, crissum, lung and so on. Bacteremia appeared with unclear primary infection focus. ＇ The bacteria and fungi infection often took place within 1 month after transplantation. The cytomegalovirus test often presented positive within 1 to 2.5 months after transplantation, and the interstitial pneumonia caused by cytomegalovirus often happened within 1 to 6 months after transplantation. ②Pathogenicbacteria distribution and drug resistance： Among the patients with autoimmune disease after AHSCT, fugus infection ranked the first （36%） , Gram-negative bacillus ranked the second （32%） and Gram-positive only amount to 4 percent. The drug resistance of Gram-negative bacillus is high in test. Besides sensitive to imipenem, ceftazidime, amikacin, the chloropseudomonas were drug resistant to most of other drugs. The escherichia coil was only sensitive to aminoglycosides, and it was resistant to quinolone, the third caphalosporin and so on. ③The transplantation related factor and infection： Among the patients with autoimmune disease after AHSCT, the severe infection rate was positively related with theirs disease course （at least 3 years）, cyclophosphamide therapeutical dose before transplantation （at least 5 g）, pretreatment cyclophosphamide concentration （200 mg/kg） and the CD34^＋ call purification （X^2=4.783-8.776, P 〈 0.05）. CONCLUSION： （~Among the patients with autoimmune disease after AHSCT, the infected pathogenicbacteria give prior to Gram-negative bacillus, fugis and cytomegalovirus. The infection places are mainly seen in oral cavity, crissum and lung, and the rate of drug resistance is high. ②Besides the protopathy, the patient disease course, cyclophosphamide therapeutical dose before transplantation, pretreatment plan and the transplantation mode are all strictly related risk factor of the infection.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第33期6645-6648,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
河南省科委科技发展计划项目(001170610)
河南省自然科学基金(0411045200)~~
