Hughes John, Stabler Richard, Gaunt Michael, Karadag Tacim, Desai Nergish, Betley Jason, Ioannou Avgousta, Aryee Anna, Hearn Pasco, Marbach Helene, Patel Amita, Otter Jonathan A, Edgeworth Jonathan D, Tosas Auguet Olga
Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, King's College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
J Antimicrob Chemother. 2015 Dec;70(12):3191-9. doi: 10.1093/jac/dkv248. Epub 2015 Aug 27.
Both low-level mupirocin resistance (LMR) and high-level mupirocin resistance (HMR) have been identified. The aim of this study was to determine the epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used mupirocin for targeted decolonization as part of successful institutional control programmes.
All MRSA identified in three microbiology laboratories serving five central and south-east London hospitals and surrounding communities between November 2011 and February 2012 were included. HMR and LMR were determined by disc diffusion testing. WGS was used to derive multilocus sequence types (MLSTs) and the presence of HMR and LMR resistance determinants.
Prevalence of either HMR or LMR amongst first healthcare episode isolates from 795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70-8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not significantly different in isolates identified from inpatients at each microbiology laboratory, but was more common in genotypically defined 'hospital' rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was associated with inpatient stay, previous history of MRSA and age ≥65 years; HMR was associated with age ≥65 years and residential postcode outside London. LMR and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22 compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR. V588F mutation and mupA carriage had high specificity (>97%) and area under the curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations in or near the mupA gene were found in eight isolates that carried mupA but were not HMR.
Mupirocin resistance was identified in <10% of patients and varied significantly by clone, implying that changes in clonal epidemiology may have an important role in determining the prevalence of resistance in conjunction with selection due to mupirocin use.
已鉴定出低水平莫匹罗星耐药（LMR）和高水平莫匹罗星耐药（HMR）。本研究的目的是确定在五家医院的耐甲氧西林金黄色葡萄球菌（MRSA）分离株中LMR和HMR的流行病学情况，这些医院已将莫匹罗星用于目标性去定植，作为成功的机构控制计划的一部分。
纳入2011年11月至2012年2月期间在为伦敦市中心和东南部五家医院及周边社区服务的三个微生物实验室中鉴定出的所有MRSA。通过纸片扩散试验确定HMR和LMR。全基因组测序（WGS）用于推导多位点序列类型（MLSTs）以及HMR和LMR耐药决定因素的存在情况。
在795例已确诊患者的首次医疗事件分离株中，HMR或LMR的患病率为9.69%（95%置信区间7.72 - 11.96）；LMR为6.29%（95%置信区间4.70 - 8.21），HMR为3.40%（95%置信区间2.25 - 4.90）。在每个微生物实验室从住院患者中鉴定出的分离株中，莫匹罗星耐药情况无显著差异，但在基因型定义的“医院”分离株中比“社区”分离株更常见（比值比3.17，95%置信区间1.36 - 9.30，P = 0.002）。LMR与住院时间、既往MRSA病史和年龄≥65岁相关；HMR与年龄≥65岁和伦敦以外的居住邮政编码相关。LMR和HMR因克隆而异，与英国主要的MRSA克隆ST22相比，LMR在ST8、ST36和ST239/241中较低，HMR在ST8和ST36中较低。V588F突变和携带mupA对鉴别表型莫匹罗星耐药具有高特异性（>97%）和曲线下面积（>83%），但敏感性点估计周围的不确定性很大（95%置信区间52.50% - 94.44%）。在八个携带mupA但不是HMR的分离株中发现了mupA基因内或附近的突变。
在<10%的患者中鉴定出莫匹罗星耐药，且因克隆而异，这意味着克隆流行病学的变化可能在与莫匹罗星使用导致的选择共同决定耐药流行率方面发挥重要作用。
