Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore.
Clin Infect Dis. 2017 May 15;64(suppl_2):S68-S75. doi: 10.1093/cid/cix113.
Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore.
Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters.
Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected.
Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.
自 2010 年以来，新加坡碳青霉烯类耐药肠杆菌科（CRE）的发病率一直在上升。我们分析了新加坡成年住院患者中 CRE 的临床和分子流行病学。
根据 2010 年至 2015 年期间公立医院向国家公共卫生实验室提交的强制性数据，估算出每 100000 个患者日有阳性临床和监测培养物的独特患者（每 100000 个患者日）的季度发病率。2013 年 12 月至 2015 年 4 月期间，从 6 家公立医院前瞻性招募 CRE 阳性成年住院患者。研究对象回答了标准化的流行病学问卷，并提供了用于本研究的样本。进一步从研究对象的电子病历中提取了更多临床信息。对研究分离株进行全基因组测序以确定传播簇。
2010 年至 2012 年底首次增加后，成年住院患者 CRE 临床培养的发病率在 2013 年（范围：7.73 至 10.32 每 100000 个患者日）趋于稳定。我们前瞻性地招募了 249 名患者。他们的中位年龄为 65 岁，108 名（43%）为女性，161 名（64.7%）为产碳青霉烯酶肠杆菌科（CPE）。多变量分析显示，先前使用碳青霉烯类药物（比值比：3.23；95%置信区间：1.67-6.25）和血液恶性肿瘤（比值比：2.85；95%置信区间：1.10-7.41）与非产碳青霉烯酶 CRE（NCPE）（n = 88）相比，与 CPE（n = 161）患者相比，与产碳青霉烯酶 CRE（CPE）（n = 161）患者相比。在 249 名患者的 430 株 CRE 分离株中，307 株（71.3%）为 CPE，其中 154 株（50.2%）为 blaKPC 阳性，97 株（31.6%）为 blaNDM 阳性，42 株（13.7%）为 blaOXA 阳性。肺炎克雷伯菌（n = 180，41.9%）、大肠杆菌（n = 129，30.0%）和阴沟肠杆菌（n = 62，14.4%）是主要的肠杆菌科细菌。WGS（n = 206）显示出不同的细菌菌株类型（STs）。主要的 blaKPC 阳性质粒为 pHS102707（n = 62，55.4%），主要的 blaNDM 阳性质粒为 pNDM-ECS01（n = 46，48.9%）。检测到涉及 13 名患者的 5 个传播群。
自 2010 年引入以来，成年住院患者的临床 CRE 趋势呈快速上升后趋于稳定，这可能是由于感染预防措施和抗菌药物管理的实施。需要进一步研究以了解 CPE 的传播动态。
