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氨基糖苷类药物治疗在感染多黏菌素和碳青霉烯类耐药肠杆菌科的肾移植受者结局中的作用。

The role of therapy with aminoglycoside in the outcomes of kidney transplant recipients infected with polymyxin- and carbapenem-resistant Enterobacteriaceae.

机构信息

Working Committee for Hospital Epidemiology and Infection Control, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Bacteriology Center, Adolfo Lutz Institute, São Paulo, Brazil.

出版信息

Eur J Clin Microbiol Infect Dis. 2019 Apr;38(4):755-765. doi: 10.1007/s10096-019-03468-4. Epub 2019 Jan 24.

Abstract

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (bla, bla, and bla), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.

摘要

肾移植受者由于耐碳青霉烯肠杆菌科(CRE)而易发生感染。多粘菌素耐药 CRE(PR-CRE)感染尤其难以治疗。本研究的目的是描述肾移植受者中的 PR-CRE 感染,并确定治疗失败的危险因素。这是一项回顾性队列研究,涉及 2013 年至 2017 年期间在本中心发生 PR-CRE 感染的所有肾移植受者。通过肉汤微量稀释法测定多粘菌素 B 的最小抑菌浓度。通过聚合酶链反应鉴定耐碳青霉烯基因(bla、bla 和 bla)、氨基糖苷类耐药基因和多粘菌素耐药基因 mcr-1。在确定的 47 例 PR-CRE 感染中,除 1 例外均由肺炎克雷伯菌引起。最常见的感染类型(54.3%)是尿路感染(UTI)。10 例采用单药治疗。联合治疗方案包括 19 例双重碳青霉烯治疗、19 例口服磷霉素和 13 例阿米卡星。21 例(45.7%)发生治疗失败。使用氨基糖苷类药物的患者临床治愈率为 78.9%,而未使用该药物的患者为 37.0%(p=0.007)。多变量分析显示糖尿病是治疗失败的危险因素;发现阿米卡星的使用和 UTI 是保护因素。9 株为 RmtB 产生菌。虽然氨基糖苷类药物是治疗 PR-CRE 感染的重要选择,但氨基糖苷类耐药的出现可能对 CRE 感染的管理产生重大影响。

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