供者来源性感染对肾移植受者预后的影响

摘要: 目的探讨供者来源性感染（DDI）对肾移植受者预后的影响。方法回顾性分析82例公民逝世后器官捐献供者及其148例肾移植受者的临床资料。根据供肾灌洗液培养结果，将受者分为供肾灌洗液培养阳性组（阳性组，92例）和供肾灌洗液培养阴性组（阴性组，56例），根据受者是否发生DDI，分为DDI组（19例）和未发生DDI组（129例）。分析供肾灌洗液培养阳性菌株分布及构成比，总结受者术后感染情况及其他并发症发生情况，比较发生DDI组与未发生DDI组受者围手术期情况，分析DDI受者的治疗及预后情况。结果 148例肾移植受者中，92例供肾灌洗液培养阳性，共分离出病原菌131株，其中革兰阳性球菌占41.2%（54/131），革兰阴性杆菌占48.9%（64/131），真菌占9.9%（13/131）。148例受者中52例发生感染，其中阳性组有45%（41/92）的受者发生感染，阴性组有20%（11/56）的受者发生感染，差异有统计学意义（P=0.002）。52例感染受者最常见的感染部位为手术部位，其次为泌尿系统。共有19例受者发生DDI，发生率为12.8%，病死率为16%，与未发生DDI组受者比较，DDI组受者移植物丢失率和病死率更高、术后住院时间更长，差异均有统计学意义（均为P < 0.05）。8例发生耐碳青霉烯类肺炎克雷伯菌（CRKP）传播感染受者应用替加环素和（或）多黏菌素、碳青霉烯类药物治疗后有3例死亡，3例行移植肾切除；另外8例发生CRKP传播感染受者中，2例单独应用头孢他啶-阿维巴坦（CAZ-AVI），3例应用CAZ-AVI联合碳青霉烯类药物，3例先应用替加环素联合碳青霉烯类药物，而后应用CAZ-AVI进行挽救性治疗，经过治疗后受者均长期存活。结论 DDI可导致严重的并发症，早期针对性抗菌治疗有着积极作用。
- 肾移植 /
- 供者来源性感染 /
- 供肾灌洗液 /
- 移植肾功能延迟恢复 /
- 凝固酶阴性葡萄球菌 /
- 耐碳青霉烯类肺炎克雷伯菌 /
- 头孢他啶-阿维巴坦 /
- 替加环素
Abstract: Objective To evaluate the effect of donor-derived infection (DDI) on clinical prognosis of kidney transplant recipients. Methods Clinical data of 82 donors from donation after citizen's death and 148 kidney transplant recipients were retrospectively analyzed. According to the culture results of the lavage fluid of donor kidney, all recipients were divided into the lavage fluid culture of donor kidney positive group (positive group, n=92) and lavage fluid culture of donor kidney negative group (negative group, n=56). All recipients were assigned into the DDI group (n=19) and non-DDI group (n=129) according to whether they developed DDI or not. The distribution and composition ratio of positive strains in the lavage fluid of donor kidney were analyzed. The incidence of postoperative infection and other complications was assessed in the recipients. Perioperative conditions of the recipients were statistically compared between the DDI and non-DDI groups. The treatment efficacy and clinical prognosis of DDI recipients were evaluated. Results Among 148 recipients, 92 obtained positive culture results in the lavage fluid of donor kidney. A total of 131 pathogenic strains were isolated, including 41.2% (54/131) of Gram-positive cocci, 48.9% (64/131) of Gram-negative bacilli and 9.9%(13/131) of fungi. Among 148 recipients, 52 cases were infected. And 45% (41/92) and 20% (11/56) of the recipients were infected in the positive and negative group, respectively. Statistical significance was noted between two groups (P=0.002). Surgical site was the most common infection site in 52 infected recipients, followed by the urinary system. Nineteen recipients developed DDI with an incidence rate of 12.8% and fatality of 16%. Compared with the non-DDI recipients, DDI recipients had significantly higher graft loss rate and fatality, and longer postoperative hospital stay (all P < 0.05). Eight cases presented with carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, after treatment with tigecycline and/or polymyxin and carbapenems, 3 cases died, and 3 underwent kidney graft resection. In the other 8 recipients with CRKP infection, 2 cases were treated with ceftazidime-avibactam (CAZ-AVI) alone, 3 treated with CAZ-AVI combined with carbapenems, and 3 initially treated with tigecycline combined with carbapenems followed by CAZ-AVI for salvage treatment. After corresponding treatment, the recipients achieved long-term survival. Conclusions DDI may lead to severe complications, while early specific antibacterial treatment plays a positive role.
- Kidney transplantation /
- Donor-derived infection /
- Lavage fluid of donor kidney /
- Delayed graft function /
- Coagulase-negative staphylococci /
- Carbapenem-resistant Klebsiella pneumoniae /
- Ceftazidime-avibactam /
- Tigecycline

HTML全文

下载: 全尺寸图片幻灯片

表 1 供肾灌洗液培养阳性菌株分布情况

Table 1. Distribution of positive strains in the lavage fluid culture of donor kidney

阳性菌株（n=131）	构成比[n（%）]
革兰阳性球菌
金黄色葡萄球菌	3（2.3）
CoNS	39（29.8）
屎肠球菌	8（6.1）
粪肠球菌	3（2.3）
无乳链球菌	1（0.8）
革兰阴性杆菌
肺炎克雷伯菌	30（22.9）
阴沟肠杆菌	7（5.3）
大肠埃希菌	16（12.2）
鲍曼不动杆菌	6（4.6）
其他	5（3.8）
真菌
白假丝酵母菌	2（1.5）
热带假丝酵母菌	2（1.5）
近平滑假丝酵母菌	6（4.6）
其他	3（2.3）

下载: 导出CSV

表 2 肾移植受者术后感染及其他并发症发生情况

Table 2. Postoperative infection and other complications in kidney transplant recipients [n(%)]

指标	阳性组（n=92）	阴性组（n=56）	P值
术后感染	41（45）	11（20）	0.002
急性排斥反应	30（33）	25（45）	0.163
DGF	28（30）	9（16）	0.054
移植肾丢失	4（4）	0	0.298
死亡	6（7）	1（2）	0.254

下载: 导出CSV

表 3 DDI与未发生DDI受者围手术期情况比较

Table 3. Comparison of perioperative situation between recipients with and without DDI

指标	DDI组（n=19）	未发生DDI组（n=129）	P值
ATG诱导[n（%）]	9（47）	64（50）	1.000
DGF[n（%）]	6（32）	31（24）	0.571
移植肾丢失[n（%）]	3（16）	1（1）	0.007
移植肾出血[n（%）]	1（5）	3（2）	0.426
死亡[n（%）]	3（16）	4（3）	0.045
术后ICU^①入住时间[M（Q₂₅，Q₇₅），d]	0（0，1）	0（0，0）	0.453
术后住院时间[M（Q₂₅，Q₇₅），d]	37（21，96）	23（20，30）	0.013
注：①ICU为重症监护室。

下载: 导出CSV

表 4 19例发生DDI受者的临床资料

Table 4. Clinical data of 19 cases of DDI recipients

例序	性别	年龄（岁）	灌洗液中分离出的病原体	术后首次培养阳性时间（d）	病原菌检出部位	抗生素方案及持续时间	住院时间（d）	DGF	结局
1	男	29	CRKP	7	引流液+尿液+气道分泌物	替加环素+亚胺培南35 d，亚胺培南+万古霉素8 d	211	无	死亡
2	男	37	CRKP	2	血液+引流液	替加环素7 d，替加环素+亚胺培南3 d	30	无	死亡
3	男	34	CRKP	10	血液+尿液+引流液	替加环素+美罗培南25 d，多黏菌素5 d	191	无	移植肾丢失
4	男	23	CRKP	15	血液+肾周组织	替加环素+亚胺培南20 d，亚胺培南13 d	111	无	移植肾丢失
5	男	51	屎肠球菌	6	引流液	头孢哌酮钠-舒巴坦钠+万古霉素16 d	23	无	存活
6	男	49	CRKP	15	引流液+血液+气道分泌物	替加环素17 d，亚胺培南28 d	236	无	移植肾丢失
7	女	46	CRKP	3	血液	替加环素+头孢哌酮钠-舒巴坦钠7 d	11	无	死亡
8	女	48	CRKP+ 屎肠球菌	1	血液	替加环素+美罗培南+万古霉素14 d	23	有	存活
9	女	19	CRKP	13	引流液	CAZ-AVI 7 d	23	无	存活
10	女	23	CRKP	12	引流液	CAZ-AVI 7 d	37	无	存活
11	男	31	CRKP	2	血液	替加环素+美罗培南11 d	18	无	存活
12	女	37	CRKP	4	血液+引流液	CAZ-AVI+美罗培南14 d	96	有	存活
13	男	44	CRKP	4	血液+尿液+引流液	替加环素+美罗培南5 d，CAZ-AVI 14 d	89	有	存活
14	男	37	CRKP	5	引流液	CAZ-AVI+美罗培南12 d	20	无	存活
15	男	55	CRKP	5	引流液	CAZ-AVI+美罗培南14 d，CAZ-AVI 7 d	55	有	存活
16	男	36	屎肠球菌	5	引流液	万古霉素+头孢哌酮钠-舒巴坦钠14 d	58	有	存活
17	男	52	CRKP	4	引流液	替加环素+美罗培南3 d，CAZ-AVI 16 d	48	无	存活
18	男	31	CRKP	4	血液+引流液	替加环素+美罗培南3 d，CAZ-AVI 14 d	21	无	存活
19	男	35	热带假丝酵母菌	5	引流液	头孢哌酮钠-舒巴坦钠+卡泊芬净14 d	20	有	存活

下载: 导出CSV

参考文献(27)

[1]	VIGARA LA, VILLANEGO F, CAZORLA JM, et al. Characteristics and evolution of renal transplant recipients infected by carbapenemase-producing Klebsiella pneumonia[J]. Transplant Proc, 2020, 52(2): 519-522. DOI: 10.1016/j.transproceed.2019.09.017.
[2]	WANG Y, LEI H, ZHANG Y, et al. Epidemiology of carbapenem-resistant Klebsiella pneumoniae bloodstream infections after renal transplantation from donation after cardiac death in a Chinese hospital: a case series analysis[J]. Antimicrob Resist Infect Control, 2018, 7: 66. DOI: 10.1186/s13756-018-0355-8.
[3]	CAMARGO JF. Donor-derived infections in solid organ transplant recipients: challenging the 30-day paradigm[J]. Transpl Infect Dis, 2017, 19(2). DOI: 10.1111/tid.12665.
[4]	CORBEL A, LADRIÈRE M, LE BERRE N, et al. Microbiological epidemiology of preservation fluids in transplanted kidney: a nationwide retrospective observational study[J]. Clin Microbiol Infect, 2020, 26(4): 475-484. DOI: 10.1016/j.cmi.2019.07.018.
[5]	RANGHINO A, DIENA D, SIMONATO F, et al. Clinical impact of bacterial contamination of perfusion fluid in kidney transplantation[J]. Springerplus, 2016, 5: 7. DOI: 10.1186/s40064-015-1658-3.
[6]	JASIAK-PANEK NM, WENZLER E, PATEL S, et al. A randomized, open-label pharmacokinetic trial of tacrolimus extended-release dosing in obese de novo kidney transplant recipients[J]. Clin Transplant, 2019, 33(8): e13640. DOI: 10.1111/ctr.13640.
[7]	RETICKER A, LICHVAR A, WALSH M, et al. The significance and impact of screening preservation fluid cultures in renal transplant recipients[J]. Prog Transplant, 2021, 31(1): 40-46. DOI: 10.1177/1526924820978608.
[8]	YU X, WANG R, PENG W, et al. Incidence, distribution and clinical relevance of microbial contamination of preservation solution in deceased kidney transplant recipients: a retrospective cohort study from China[J]. Clin Microbiol Infect, 2019, 25(5): 595-600. DOI: 10.1016/j.cmi.2018.12.040.
[9]	ORIOL I, SABÉ N, TEBÉ C, et al. Clinical impact of culture-positive preservation fluid on solid organ transplantation: a systematic review and Meta-analysis[J]. Transplant Rev (Orlando), 2018, 32(2): 85-91. DOI: 10.1016/j.trre.2017.11.003.
[10]	ORIOL I, SABE N, CÀMARA J, et al. The impact of culturing the organ preservation fluid on solid organ transplantation: a prospective multicenter cohort study[J]. Open Forum Infect Dis, 2019, 6(6): ofz180. DOI: 10.1093/ofid/ofz180.
[11]	何莉, 林栋栋, 刘晋宁, 等. 公民器官捐献供者感染现状与应对的回顾性研究[J]. 北京医学, 2019, 41(6): 472- 475. DOI: 10.15932/j.0253-9713.2019.06.009. HE L, LIN DD, LIU JN, et al. A retrospective study on the current situation and coping strategies of organ donor infection[J]. Beijing Med J, 2019, 41(6): 472-475. DOI: 10.15932/j.0253-9713.2019.06.009.
[12]	ORIOL I, LLADÓ L, VILA M, et al. The etiology, incidence, and impact of preservation fluid contamination during liver transplantation[J]. PLoS One, 2016, 11(8): e0160701. DOI: 10.1371/journal.pone.0160701.
[13]	赵纪强, 霍枫, 汪邵平, 等. 公民逝世后器官捐献肝移植保存液污染: 基于78例单中心对照研究[J]. 分子影像学杂志, 2019, 42(4): 538-543. DOI: 10.12122/j.issn.1674-4500.2019.04.27. ZHAO JQ, HUO F, WANG SP, et al. Single-center analysis on preservation solution contamination and initial experience of liver transplantation from organ donation by citizens after death[J]. J Mol Imaging, 2019, 42(4): 538-543. DOI: 10.12122/j.issn.1674-4500.2019.04.27.
[14]	AL MIDANI A, HOOKHAM L, BANGA N, et al. The value of perfusion fluid culture analysis in deceased donor renal transplants: a 10-year single-center experience[J]. Transplant Proc, 2021, 53(6): 1808-1812. DOI: 10.1016/j.transproceed.2021.03.023.
[15]	郭琛, 刘剑, 纪建磊, 等. 供肾保存液的培养结果分析及临床意义[J]. 中华器官移植杂志, 2018, 39(10): 602-605. DOI: 10.3760/cma.j.issn.0254-1785.2018.10.006. GUO C, LIU J, JI JL, et al. Analysis and clinical significance of culture results of donor renal perfusate[J]. Chin J Organ Transplant, 2018, 39(10): 602-605. DOI: 10.3760/cma.j.issn.0254-1785.2018.10.006.
[16]	GRĄT M, LIGOCKA J, LEWANDOWSKI Z, et al. Incidence, pattern and clinical relevance of microbial contamination of preservation fluid in liver transplantation[J]. Ann Transplant, 2012, 17(3): 20-28. DOI: 10.12659/aot.883454.
[17]	MEIER RPH, ANDREY DO, SUN P, et al. Pancreas preservation fluid microbial contamination is associated with poor islet isolation outcomes - a multi-centre cohort study[J]. Transpl Int, 2018, 31(8): 917-929. DOI: 10.1111/tri.13159.
[18]	SOTIROPOULOS GC, KOSTAKIS ID, PRODROMIDOU A, et al. Contamination of the preservation solution in solid organ transplantation[J]. Transplant Proc, 2019, 51(2): 392-395. DOI: 10.1016/j.transproceed.2019.01.070.
[19]	WANG Z, QIAN Y, BAI H, et al. Allograft hemorrhage as a manifestation of carbapenem-resistant Klebsiella pneumonia infection in kidney transplant recipients: case series[J]. Medicine (Baltimore), 2020, 99(13): e18982. DOI: 10.1097/MD.0000000000018982.
[20]	YE QF, ZHOU W, WAN QQ. Donor-derived infections among Chinese donation after cardiac death liver recipients[J]. World J Gastroenterol, 2017, 23(31): 5809-5816. DOI: 10.3748/wjg.v23.i31.5809.
[21]	CERUTTI E, STRATTA C, ROMAGNOLI R, et al. Bacterial- and fungal-positive cultures in organ donors: clinical impact in liver transplantation[J]. Liver Transpl, 2006, 12(8): 1253-1259. DOI: 10.1002/lt.20811.
[22]	BUNSOW E, LOS-ARCOS I, MARTIN-GÓMEZ MT, et al. Donor-derived bacterial infections in lung transplant recipients in the era of multidrug resistance[J]. J Infect, 2020, 80(2): 190-196. DOI: 10.1016/j.jinf.2019.12.006.
[23]	MARTIN-LOECHES I, RODRIGUEZ AH, TORRES A. New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe[J]. Curr Opin Crit Care, 2018, 24(5): 347-352. DOI: 10.1097/MCC.0000000000000535.
[24]	中华医学会器官移植学分会. 器官移植供者来源性感染诊疗技术规范(2019版)[J]. 器官移植, 2019, 10(4): 369-375. DOI: 10.3969/j.issn.1674-7445.2019.04.005. Branch of Organ Transplantation of Chinese Medical Association. Technical specification for diagnosis and treatment of donor-derived infection in organ transplantation (2019 edition)[J]. Organ Transplant, 2019, 10(4): 369-375. DOI: 10.3969/j.issn.1674-7445.2019.04.005.
[25]	BENAMU E, WOLFE CR, MONTOYA JG. Donor-derived infections in solid organ transplant patients: toward a holistic approach[J]. Curr Opin Infect Dis, 2017, 30(4): 329-339. DOI: 10.1097/QCO.0000000000000377.
[26]	WAN Q, LIU H, YE S, et al. Confirmed transmission of bacterial or fungal infection to kidney transplant recipients from donated after cardiac death (DCD) donors in China: a single-center analysis[J]. Med Sci Monit, 2017, 23: 3770-3779. DOI: 10.12659/msm.901884.
[27]	SATLIN MJ, WALSH TJ. Multidrug-resistant enterobacteriaceae, pseudomonas aeruginosa, and vancomycin-resistant enterococcus: three major threats to hematopoietic stem cell transplant recipients[J]. Transpl Infect Dis, 2017, 19(6): 10.1111/tid. 12762. DOI: 10.1111/tid.12762.