Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore 169608, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, Singapore 117549, Singapore.
Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore 169608, Singapore; Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Int J Antimicrob Agents. 2019 May;53(5):657-662. doi: 10.1016/j.ijantimicag.2019.03.011. Epub 2019 Mar 14.
Increasing resistance to polymyxin, a last-line antibiotic, is a growing public health concern worldwide. The primary objective of this study was to identify predictors for the isolation of polymyxin-resistant (PR) carbapenem-resistant Enterobacteriaceae (CRE) among hospitalized patients. The secondary objective was to describe the clinical outcomes of patients with PR-CRE infections. A retrospective case-control study including patients admitted to Singapore General Hospital between June 2012 and June 2016 was conducted. Cases were defined as patients who had clinical cultures from which a PR-CRE was isolated. Controls were randomly selected from patients with polymyxin-susceptible (PS) CRE admitted during the same period, and frequency-matched to site of isolation. We included 37 PR cases and 111 PS controls. Polymyxin resistance was detected predominantly in Enterobacter spp. (54.1%) and Klebsiella pneumoniae (43.2%). Multilocus sequence typing showed little clonal relatedness among the isolates. mcr-1 was detected in two PR-CRE isolates. Multivariable analyses showed that PR-CRE isolation was associated with prior polymyxins (adjusted odds ratio (OR), 21.31; 95% confidence interval (CI), 3.04-150.96) and carbapenem exposures (OR 3.74; CI 1.13-12.44), when adjusted for time at risk and bacteria species. In PR-CRE patients with infections, the 30-day all-cause in-hospital mortality was 50.0% as compared to 38.1% in patients with PS-CRE (P = 0.346). Prior polymyxin and carbapenem exposures were independent risk factors for isolation of PR-CRE. Outcomes of PR-CRE and PS-CRE infections were similar in this study.
对多粘菌素这种最后一线抗生素的耐药性日益增强，是全球日益严重的公共卫生问题。本研究的主要目的是确定住院患者中分离出多粘菌素耐药（PR）碳青霉烯类耐药肠杆菌科（CRE）的预测因素。次要目的是描述 PR-CRE 感染患者的临床结局。这是一项回顾性病例对照研究，纳入了 2012 年 6 月至 2016 年 6 月期间在新加坡总医院住院的患者。病例定义为从其临床培养物中分离出 PR-CRE 的患者。对照组随机从同期住院的多粘菌素敏感（PS）CRE 患者中选择，并按分离部位与病例相匹配。我们纳入了 37 例 PR 病例和 111 例 PS 对照。多粘菌素耐药主要见于肠杆菌属（54.1%）和肺炎克雷伯菌（43.2%）。多位点序列分型显示，分离株之间的克隆相关性很小。在 2 株 PR-CRE 分离株中检测到 mcr-1。多变量分析显示，在调整风险时间和细菌种类后，PR-CRE 分离与先前使用多粘菌素（调整后的优势比（OR）21.31；95%置信区间（CI）3.04-150.96）和碳青霉烯类药物暴露（OR 3.74；CI 1.13-12.44）有关。在 PR-CRE 感染患者中，30 天全因院内死亡率为 50.0%，而 PS-CRE 患者为 38.1%（P=0.346）。先前使用多粘菌素和碳青霉烯类药物是分离出 PR-CRE 的独立危险因素。在本研究中，PR-CRE 和 PS-CRE 感染的结局相似。
