Department of Pharmacy, Singapore General Hospital, Singapore, Singapore.
PLoS One. 2012;7(3):e34254. doi: 10.1371/journal.pone.0034254. Epub 2012 Mar 26.
Increasing prevalence of ertapenem-resistant, carbapenem-susceptible Enterobacteriaceae (ERE) in Singapore presents a major therapeutic problem. Our objective was to determine risk factors associated with the acquisition of ERE in hospitalized patients; to assess associated patient outcomes; and to describe the molecular characteristics of ERE.
A retrospective case-case-control study was conducted in 2009 at a tertiary care hospital. Hospitalized patients with ERE and those with ertapenem-sensitive Enterobacteriaceae (ESE) were compared with a common control group consisting of patients with no prior gram-negative infections. Risk factors analyzed included demographics; co-morbidities; instrumentation and antibiotic exposures. Two parallel multivariate logistic regression models were performed to identify independent variables associated with ERE and ESE acquisition respectively. Clinical outcomes were compared between ERE and ESE patients.
Twenty-nine ERE cases, 29 ESE cases and 87 controls were analyzed. Multivariate logistic regression showed that previous hospitalization (Odds ratio [OR], 10.40; 95% confidence interval [CI], 2.19-49.20) and duration of fluoroquinolones exposure (OR, 1.18 per day increase; 95% CI, 1.05-1.34) were unique independent predictors for acquiring ERE. Duration of 4(th)-generation cephalosporin exposure was found to predict for ESE acquisition (OR, 1.63 per day increase; 95% CI, 1.05-2.54). In-hospital mortality rates and clinical response rates were significantly different between ERE and ESE groups, however ERE infection was not a predictor of mortality. ERE isolates were clonally distinct. Ertapenem resistance was likely to be mediated by the presence of extended-spectrum β-lactamases or plasmid-borne AmpC in combination with impermeability due to porin loss and/or efflux pumps.
Prior hospitalization and duration of fluoroquinolone treatment were predictors of ERE acquisition. ERE infections were associated with higher mortality rates and poorer clinical response rates when compared to ESE infections.
在新加坡，耐厄培南、碳青霉烯敏感肠杆菌科（ERE）的发病率不断上升，这给治疗带来了很大的难题。我们的目的是确定住院患者获得 ERE 的相关危险因素；评估相关的患者结局；并描述 ERE 的分子特征。
2009 年，我们在一家三级保健医院进行了一项回顾性病例对照研究。将 ERE 患者和耐厄培南敏感肠杆菌科（ESE）患者与无革兰阴性菌感染史的普通对照组进行比较。分析的危险因素包括人口统计学特征；合并症；仪器和抗生素暴露。我们进行了两个平行的多变量逻辑回归模型，以确定分别与 ERE 和 ESE 获得相关的独立变量。比较了 ERE 和 ESE 患者的临床结局。
共分析了 29 例 ERE 病例、29 例 ESE 病例和 87 例对照。多变量逻辑回归显示，既往住院（比值比[OR]，10.40；95%置信区间[CI]，2.19-49.20）和氟喹诺酮类药物暴露时间（OR，每天增加 1.18；95%CI，1.05-1.34）是获得 ERE 的独特独立预测因素。4 代头孢菌素暴露时间的增加与 ESE 获得有关（OR，每天增加 1.63；95%CI，1.05-2.54）。ERE 和 ESE 组的住院死亡率和临床反应率有显著差异，但 ERE 感染不是死亡率的预测因素。ERE 分离株的克隆是不同的。厄培南耐药可能是由于外膜孔蛋白缺失和/或外排泵导致通透性降低，同时存在超广谱β-内酰胺酶或质粒携带的 AmpC 引起的。
既往住院和氟喹诺酮类药物治疗时间是获得 ERE 的预测因素。与 ESE 感染相比，ERE 感染与更高的死亡率和更差的临床反应率相关。
