Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
Int J Antimicrob Agents. 2016 Apr;47(4):324-7. doi: 10.1016/j.ijantimicag.2016.01.005. Epub 2016 Feb 15.
Tigecycline (TIG) resistance is a growing concern because this antibiotic is regarded as one of the last resorts to treat infections caused by multidrug-resistant and extensively drug-resistant (XDR) bacteria. Information regarding TIG-resistant Escherichia coli isolates is scarce. In this study, we report the emergence of high-level TIG resistance in a longitudinal series of XDR E. coli isolates collected during TIG treatment. Whole-genome sequencing was performed for six E. coli strains harbouring bla(NDM-5) and genomic comparison revealed two amino acid substitutions. Mutation in rpsJ could be a significant factor conferring TIG resistance in these isolates. The fitness cost of TIG resistance in resistant strains was evaluated by determining the relative growth rate, indicating that TIG resistance reduced fitness by ca. 7%. This study is the first report to demonstrate high-level TIG resistance in E. coli in vivo. In addition, we report the first treatment-emergent minimum inhibitory concentration (MIC) development of TIG from 1mg/L to 64 mg/L in E. coli. Clinicians should be aware of the risk of an increase in the MIC of TIG under therapy.
替加环素（TIG）耐药性日益受到关注，因为这种抗生素被视为治疗多药耐药和广泛耐药（XDR）细菌感染的最后手段之一。关于替加环素耐药大肠埃希菌分离株的信息很少。在这项研究中，我们报告了在替加环素治疗期间收集的一系列 XDR 大肠埃希菌分离株中出现高水平替加环素耐药的情况。对携带 bla(NDM-5) 的 6 株大肠埃希菌菌株进行了全基因组测序，基因组比较显示了两个氨基酸替换。rpsJ 中的突变可能是这些分离株中替加环素耐药的重要因素。通过测定相对生长率来评估耐药菌株中替加环素耐药的适应性代价，表明替加环素耐药性降低了约 7%的适应性。本研究首次证明了大肠埃希菌体内高水平的替加环素耐药性。此外，我们报告了首例治疗中替加环素最低抑菌浓度（MIC）从 1mg/L 增加到 64mg/L 的情况。临床医生应该意识到治疗过程中替加环素 MIC 增加的风险。
