Findlay Jacqueline, Hopkins Katie L, Loy Richard, Doumith Michel, Meunier Danièle, Hill Robert, Pike Rachel, Mustafa Nazim, Livermore David M, Woodford Neil
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London NW9 5EQ, UK.
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
J Antimicrob Chemother. 2017 May 1;72(5):1340-1349. doi: 10.1093/jac/dkx012.
OXA-48-like carbapenemases have spread worldwide since 2001. We analysed patient and microbiological data for UK isolates with these enzymes as confirmed by the national reference laboratory from November 2007 to December 2014.
MICs were determined using BSAC agar dilution. Isolates with reduced susceptibility or resistance to at least one carbapenem and high-level resistance to both piperacillin/tazobactam (MICs ≥64 mg/L) and temocillin (MICs ≥128 mg/L) were screened by PCR for bla OXA-48-like genes. The genomes of about half of the isolates were sequenced, with MLST types, resistance genes and plasmid replicon types inferred. Patient data provided by sending laboratories were reviewed.
Isolates ( n = 741) with OXA-48-like carbapenemases were submitted from 111 UK laboratories, representing 536 patients. Almost all (99%; 736 of 741) were Enterobacteriaceae, predominantly Klebsiella pneumoniae (55%; 408), and most (80%; 595) were from inpatients. WGS of 351 non-duplicate isolates identified bla OXA-48 as the most common variant, found in two-thirds (235 of 351) of isolates, followed by bla OXA-181 (68), bla OXA-232 (32), bla OXA-244 (10), bla OXA-484 (5) and bla OXA-245 (1). Among K. pneumoniae (163 of 351), Escherichia coli (114 of 351) and Enterobacter cloacae (42 of 351), 119 STs were identified. Mapping analyses revealed that 63% (222 of 351) of isolates harboured plasmids that shared >99% identity to one of four known plasmids [pOXA-48a (44%; 154 of 351), pOXA-232 (10%; 34 of 351), pOXA181 (9%; 30 of 351) and pKP3-A (1%; 4 of 351)]; the remaining 37% of isolates harboured bla OXA-48-like in unknown environments.
OXA-48-like carbapenemases are an increasing problem in the UK. This study highlights both the role of successful plasmids and the polyclonal nature of their dissemination.
自2001年以来,OXA - 48样碳青霉烯酶已在全球范围内传播。我们分析了2007年11月至2014年12月期间英国分离株的患者和微生物学数据,这些分离株经国家参考实验室确认为携带这些酶。
采用英国抗菌化疗学会(BSAC)琼脂稀释法测定最低抑菌浓度(MIC)。对至少对一种碳青霉烯类药物敏感性降低或耐药,且对哌拉西林/他唑巴坦(MIC≥64mg/L)和替莫西林(MIC≥128mg/L)均呈高水平耐药的分离株进行bla OXA - 48样基因的PCR筛查。对约一半的分离株进行全基因组测序,推断其多位点序列分型(MLST)类型、耐药基因和质粒复制子类型。对送检实验室提供的患者数据进行了审查。
来自英国111家实验室的741株携带OXA - 48样碳青霉烯酶的分离株,代表536例患者。几乎所有(99%;741株中的736株)为肠杆菌科细菌,主要是肺炎克雷伯菌(55%;408株),且大多数(80%;595株)来自住院患者。对351株非重复分离株进行全基因组测序(WGS),确定bla OXA - 48是最常见的变异型,在三分之二(351株中的235株)的分离株中发现,其次是bla OXA - 181(68株)、bla OXA - 232(32株)、bla OXA - 244(10株)、bla OXA - 484(5株)和bla OXA - 245(1株)。在肺炎克雷伯菌(351株中的163株)、大肠埃希菌(351株中的114株)和阴沟肠杆菌(351株中的42株)中,共鉴定出119种序列型(ST)。图谱分析显示,63%(351株中的222株)的分离株携带与四种已知质粒之一(pOXA - 48a,44%;351株中的154株;pOXA - 232,10%;351株中的34株;pOXA181,9%;351株中的30株;pKP3 - A,1%;351株中的4株)具有>99%同一性的质粒;其余37%的分离株在未知环境中携带bla OXA - 48样基因。
OXA - 48样碳青霉烯酶在英国正成为一个日益严重的问题。本研究突出了成功质粒的作用及其传播的多克隆性质。