National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK; Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK.
Int J Antimicrob Agents. 2018 Aug;52(2):278-282. doi: 10.1016/j.ijantimicag.2018.03.016. Epub 2018 Mar 27.
The emergence of 16S rRNA methyltransferases (16S RMTases) worldwide is a growing concern due to their ability to confer high-level resistance (minimum inhibitory concentrations (MICs) >256 mg/L) to all clinically relevant aminoglycosides. As the occurrence of 16S RMTases in the United Kingdom has not been investigated to date, we screened 806 Enterobacteriaceae isolates displaying high-level aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) for 16S RMTases either by analysing whole-genome sequence (WGS) data (which were available for 449 isolates) or by polymerase chain reaction. A total of 94.5% (762/806) pan-aminoglycoside-resistant Enterobacteriaceae were positive for one or more 16S RMTase genes; armA was the most common (340, 44.6%) followed by rmtC (146, 19.2%), rmtF (137, 18.0%), rmtB (87, 11.4%) and various two-gene combinations (52, 6.8%). Most (93.4%; 712/762) 16S RMTase producers also carried acquired carbapenemase genes, with bla the most common (592/712; 83.1%). Additionally, high-risk bacterial clones associated with bla were identified in the subset of isolates with WGS data. These included Escherichia coli sequence types (STs) 405 (21.8%, 19/87), 167 (20.7%, 18/87) 410 (12.6%, 11/87) and K. pneumoniae STs 14 (35.6%, 112/315), 231 (15.6%, 49/315) and 147 (10.5%, 33/315). These accounted for 4.2% (15/358), 5.0% (18/358), 3.1% (11/358), 28.2% (101/358), 3.1% (11/358) and 7.0% (25/358) bla-producing isolates, respectively. This study shows that 16S RMTases occur in the UK and Ireland and carbapenemases are particularly prevalent in 16S RMTase-producing Enterobacteriaceae. This association poses a risk to the treatment of multidrug-resistant Gram-negative infections in the clinical setting.
16S rRNA 甲基转移酶（16S RMTases）在全球范围内的出现引起了越来越多的关注，因为它们能够赋予所有临床相关氨基糖苷类药物高水平的耐药性（最低抑菌浓度（MICs）>256mg/L）。由于迄今为止英国尚未调查 16S RMTases 的发生情况，我们通过分析全基因组序列（WGS）数据（可用于 449 株分离株）或聚合酶链反应，对 806 株显示高水平氨基糖苷类耐药性（阿米卡星、庆大霉素和妥布霉素 MICs 分别为≥64、≥32 和≥32mg/L）的肠杆菌科分离株进行了 16S RMTase 检测。总共 94.5%（762/806）的泛氨基糖苷类耐药肠杆菌科细菌对一种或多种 16S RMTase 基因呈阳性；armA 最为常见（340 株，44.6%），其次是 rmtC（146 株，19.2%）、rmtF（137 株，18.0%）、rmtB（87 株，11.4%）和各种双基因组合（52 株，6.8%）。大多数（93.4%；712/762）16S RMTase 产生菌还携带获得性碳青霉烯酶基因，bla 最为常见（592/712；83.1%）。此外，在具有 WGS 数据的分离株亚组中鉴定出与 bla 相关的高风险细菌克隆。这些包括大肠杆菌序列类型（STs）405（21.8%，19/87）、167（20.7%，18/87）410（12.6%，11/87）和肺炎克雷伯菌 STs 14（35.6%，112/315）、231（15.6%，49/315）和 147（10.5%，33/315）。这些分别占 4.2%（15/358）、5.0%（18/358）、3.1%（11/358）、28.2%（101/358）、3.1%（11/358）和 7.0%（25/358）bla 产生菌的比例。本研究表明，16S RMTases 存在于英国和爱尔兰，而碳青霉烯酶在 16S RMTase 产生的肠杆菌科细菌中特别普遍。这种关联对临床环境中治疗多重耐药革兰氏阴性感染构成了威胁。
