Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections
Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections
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DOI：
10.1093/infdis/jit293
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发表时间：
2013-10-01
影响因子：
6.4
通讯作者：
Waterman, Paige E.
中科院分区：
文献类型：
--
作者：
Lesho, Emil;Yoon, Eun-Jeong;Waterman, Paige E.
背景粘菌素耐药性令人担忧，因为越来越需要它来治疗由对所有其他抗生素具有耐药性的细菌引起的感染，并且与较差的结果有关。从体内系列的纵向数据是稀疏的。在加强感染控制措施的质量改进指令下，对极端耐药（XDR）细菌进行表型和分子分析。在粘菌素治疗期间纵向回收了28株XDR鲍曼不动杆菌分离株。14例对粘菌素敏感，14例耐药。获得粘菌素耐药性并不改变对其他抗生素的耐药性。分离株具有低的最低抑菌浓度的研究氨基糖苷类，属于多位点序列类型94，是难以区分的脉冲场凝胶电泳和光学映射，并窝藏一个新的pmrC 1A 1B等位基因。粘菌素耐药与pmrA 1和/或pmrB基因的点突变相关。另外的pmrC同源物，命名为eptA-1和eptA-2，在远离操纵子的位置。与粘菌素敏感菌株相比，粘菌素耐药菌株显示pmrC 1A 1B，eptA-1，和eptA-2的表达显着增强;较低的生长速率;和降低健身。系统发育分析表明，黏菌素耐药菌株来自于单一的黏菌素敏感菌株。我们提供了一系列XDR A中粘菌素抗性的体内演变的见解。鲍曼不动杆菌分离株在感染治疗期间恢复，并强调抗生素管理和监测的重要性。
Background. Colistin resistance is of concern since it is increasingly needed to treat infections caused by bacteria resistant to all other antibiotics and has been associated with poorer outcomes. Longitudinal data from in vivo series are sparse.Methods. Under a quality-improvement directive to intensify infection-control measures, extremely drug-resistant (XDR) bacteria undergo phenotypic and molecular analysis.Results. Twenty-eight XDR Acinetobacter baumannii isolates were longitudinally recovered during colistin therapy. Fourteen were susceptible to colistin, and 14 were resistant to colistin. Acquisition of colistin resistance did not alter resistance to other antibiotics. Isolates had low minimum inhibitory concentrations of an investigational aminoglycoside, belonged to multi-locus sequence type 94, were indistinguishable by pulsed-field gel electrophoresis and optical mapping, and harbored a novel pmrC1A1B allele. Colistin resistance was associated with point mutations in the pmrA1 and/or pmrB genes. Additional pmrC homologs, designated eptA-1 and eptA-2, were at distant locations from the operon. Compared with colistin-susceptible isolates, colistin-resistant isolates displayed significantly enhanced expression of pmrC1A1B, eptA-1, and eptA-2; lower growth rates; and lowered fitness. Phylogenetic analysis suggested that colistin resistance emerged from a single progenitor colistin-susceptible isolate.Conclusions. We provide insights into the in vivo evolution of colistin resistance in a series of XDR A. baumannii isolates recovered during therapy of infections and emphasize the importance of antibiotic stewardship and surveillance.