肝移植术后革兰氏阳性球菌的感染特点及防治效果

Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation

目的:革兰氏阳性(Gram-positive,G^(+))球菌是引起肝移植术后早期感染的主要病原体,对肝移植受者的预后构成了巨大威胁。本研究通过分析公民逝世后器官捐献供肝肝移植术后2个月内G^(+)球菌感染的病原菌组成、耐药性、危险因素及抗G^(+)球菌抗生素使用效果,以期指导肝移植术后G^(+)球菌感染的防治。方法:回顾性收集2019年1月至2022年7月在中南大学湘雅三医院行肝移植的256例受者中39例发生的51株G^(+)球菌感染的球菌组成、耐药性及抗球菌抗生素防治效果的数据,并分析球菌感染危险因素。结果:病原菌构成中屎肠球菌处于优势(33/51,64.7%),粪肠球菌次之(11/51,21.6%)。最常见感染部位为腹腔/胆道(13/256,5.1%)及尿道(10/256,3.9%)。51次G^(+)球菌引起的感染中50次(98%)发生在肝移植术后1月内。对G+球菌最敏感的药物为替考拉宁、替加环素、利奈唑胺及万古霉素。考虑到万古霉素的肾毒性,所有病人均未使用万古霉素。达托霉素与替考拉宁预防球菌感染效果差异无统计学意义(P>0.05)。单因素分析显示术前终末期肝病模型(Model for End-stage Liver Disease,MELD)评分>25(P=0.005)、术中红细胞输注量≥12 U(P=0.013)及术后预防用抗生素>2种(P=0.003)与术后球菌感染发生相关;多因素logistic回归分析显示术前MELD评分>25分(OR=2.378,95%CI 1.124~5.032,P=0.024)及术中红细胞输注量≥12 U(OR=2.757,95%CI 1.227~6.195,P=0.014)是肝移植术后G^(+)球菌感染发生的独立危险因素,术后预防用抗生素>2种(OR=0.269,95%CI 0.121~0.598,P=0.001)的肝移植受者术后G^(+)球菌感染率降低。结论:肝移植术后早期发生的G^(+)球菌感染以腹腔/胆道及尿道的屎肠球菌感染为主。替考拉宁、替加环素及利奈唑胺均是抗G^(+)球菌敏感药物。达托霉素与替考拉宁预防G^(+)球菌感染效果相当。术前MELD评分高及术中大量输注红细胞患者术后易发生球菌感染,术后兼顾预防G^(+)球菌的大于2种抗生素的预防抗感染方案有助于减少该类感染的发生。

Objective:Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation(LT),posing a huge threat to the prognosis of liver transplant recipients.This study aims to analyze the distribution and drug resistance of Gram-positive cocci,the risk factors for infections and efficacy of antibiotics within 2 months after LT,and to guide the prevention and treatment of these infections.Methods:In this study,data of pathogenic bacteria distribution,drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens’death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022,and risk factors for Gram-positive cocci infection were analyzed.Results:Enterococcus faecium was the dominant pathogenic bacteria(33/51,64.7%),followed by Enterococcus faecalis(11/51,21.6%).The most common sites of infection were abdominal cavity/biliary tract(13/256,5.1%)and urinary tract(10/256,3.9%).Fifty(98%)of the 51 Gram-positive cocci infections occurred within 1 month after LT.The most sensitive drugs to Gram-positive cocci were teicoplanin,tigecycline,linezolid and vancomycin.Vancomycin was not used in all patients,considering its nephrotoxicity.Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection(P>0.05).Univariate analysis indicated that preoperative Model for End-Stage Liver Disease(MELD)score>25(P=0.005),intraoperative red blood cell infusion≥12 U(P=0.013)and exposure to more than 2 intravenous antibiotics post-LT(P=0.003)were related to Gram-positive cocci infections.Multivariate logistic regression analysis revealed that preoperative MELD score>25(OR=2.378,95%CI 1.124 to 5.032,P=0.024)and intraoperative red blood cell transfusion≥12 U(OR=2.757,95%CI 1.227 to 6.195,P=0.014)were independent risk factors for Gram-positive cocci infections after LT.Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT(OR=0.269,95%CI 0.121 to 0.598,P=0.001).Conclusion:Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract.Teicoplanin,tigecycline and linezolid were anti-cocci sensitive drugs.Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci.Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery.Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.