Tigecycline resistance caused by rpsJ evolution in a 59-year-old male patient infected with KPC-producing Klebsiella pneumoniae during tigecycline treatment
Tigecycline resistance caused by rpsJ evolution in a 59-year-old male patient infected with KPC-producing Klebsiella pneumoniae during tigecycline treatment
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一名 59 岁男性患者在替加环素治疗期间感染产 KPC 肺炎克雷伯菌，由 rpsJ 进化引起替加环素耐药
DOI：
10.1016/j.meegid.2018.09.025
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发表时间：
2018-12-01
影响因子：
3.2
通讯作者：
Du, Xiaoxing
中科院分区：
文献类型：
--
作者：
He, Fang;Shi, Qiucheng;Du, Xiaoxing
耐碳青霉烯类肺炎克雷伯菌（CRKP）医院感染近年来迅速增加。到目前为止，CRKP感染的抗感染药物有限。替加环素是CRKP感染的最后治疗手段之一。在这项研究中，替加环素治疗的疗效进行了监测，在59岁的男性患者感染的KPC生产的K。肺炎。连续克隆一致K.在替加环素治疗期间培养肺炎分离株。对分离株进行全基因组测序，并进一步进行生物信息学分析。共收集到5个菌株，其中4个为敏感菌株，1个为抗性菌株。所有分离株均属于序列类型11（ST 11），携带包括B/a（KPC-2）在内的11个与抗生素耐药相关的基因序列。在替加环素耐药分离株中鉴定出rpsJ中的一个氨基酸取代V57 L。随后的转化实验证实了rpsJ变体（V57 L）对降低替加环素敏感性的贡献。据我们所知，这项研究是第一个报告，提供直接的体内证据，在rpsJ基因的演变，可导致替加环素耐药的患者感染KPC产生的K。替加环素治疗期间感染肺炎。这一发现作为治疗警告，因为rpsJ基因位于CRKP菌株的染色体上。在替加环素的选择压力下，可能发生rpsJ突变并导致替加环素耐药。
Carbapenem resistant Klebsiella pneumoniae (CRKP) nosocomial infection increased rapidly in recent years. By far, the anti-infection drugs for CRKP infection are limited. Tigecycline is one of the last resort treatments for CRKP infections. In this study, curative effect of tigecycline therapy was monitored in a 59-year-old male patient infected with KPC-producing K. pneumoniae. Consecutive clonal consistent K. pneumoniae isolates were cultured during tigecycline treatment. Whole genome sequencing of the isolates was performed, and bioinformatics analysis was further performed. Five isolates, four of which were susceptible and one resistant were collected. All of the isolates belong to Sequence Type 11 (ST11), and harbouring 11 gene sequences relevant to antibiotic resistance including b/a(KPC-2). One amino acid substitution V57L in rpsJ was identified in the tigecycline resistant isolates. Subsequent transformation experiment confirmed the contribution of the rpsJ variant (V57L) to reduced tigecycline susceptibility. To our knowledge, this study is the first report to provide direct in vivo evidence that evolution in the rpsJ gene can lead to tigecycline resistance in patients infected with KPC-producing K. pneumoniae during tigecycline treatment. This finding serves as a therapeutic warning as the rpsJ gene is on the chromosome of CRKP strains. Under selective pressure from tigecycline, the rpsJ mutation may occur and lead to tigecycline resistant.