ESBL colonization and acquisition in a hospital population: The molecular epidemiology and transmission of resistance genes

A prospective cohort study (German Clinical Trial Registry, No. 00005273) was performed to determine pre-admission colonization rates, hospital acquisition risk factors, subsequent infection rates and colonization persistence including the respective molecular epidemiology and transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE). A total of 342 EPEs were isolated from rectal swabs of 1,334 patients on admission, at discharge and 6 months after hospitalization. Inclusion criteria were patients’ age > 18 years, expected length of stays > 48 hours, external referral. The EPEs were characterized by routine microbiological methods, a DNA microarray and ERIC-PCR. EPE colonization was found in 12.7 % of admitted patients, with the highest rate (23.8 %) in patients from nursing homes. During hospitalization, 8.1 % of the patients were de novo EPE colonized, and invasive procedures, antibiotic and antacid therapies were independent risk factors. Only 1/169 patients colonized on admission developed a hospital-acquired EPE infection. Escherichia coli was the predominant EPE (88.9 %), and 92.1% of the ESBL phenotypes could be related to CTX-M variants with CTX-M-1/15 group being most frequent (88.9%). A corresponding β-lactamase could not be identified in five isolates. Hospital-acquired EPE infections in patients colonized before or during hospitalization were rare. The diversity of the EPE strains was much higher than that of the underlying plasmids. In seven patients, transmission of the respective plasmid across different species could be observed indicating that the current strain-based surveillance approaches may underestimate the risk of inter-species transmission of resistance genes.

本研究为一项前瞻性队列研究，已在德国临床试验注册中心（German Clinical Trial Registry）完成注册，注册号为00005273，旨在探究产超广谱β-内酰胺酶（extended-spectrum β-lactamase, ESBL）肠杆菌科（EPE）的入院前定植率、医院获得性危险因素、后续感染率、定植持续时间，及其对应的分子流行病学特征与传播速率。本研究共从1334例患者的直肠拭子样本中分离得到342株EPE，采样时点分别为入院时、出院时及出院后6个月。本研究的纳入标准为：患者年龄大于18岁、预计住院时长超过48小时且为外部转诊患者。研究采用常规微生物学检测方法、DNA微阵列技术及ERIC-PCR对分离得到的EPE进行分型鉴定。入院患者的EPE总体定植率为12.7%，其中来自养老机构的患者定植率最高，达23.8%。住院期间，共有8.1%的患者新发EPE定植；侵入性操作、抗菌药物治疗及抗酸剂治疗为新发定植的独立危险因素。仅1/169例入院时已发生EPE定植的患者，后续出现了医院获得性EPE感染。大肠埃希菌（Escherichia coli）为最主要的EPE菌株，占总分离株的88.9%；92.1%的ESBL表型与CTX-M型酶变体相关，其中CTX-M-1/15群最为常见，占比达88.9%。另有5株分离株未检测到对应的β-内酰胺酶。入院前或住院期间已定植的患者发生医院获得性EPE感染的情况较为罕见。EPE菌株的遗传多样性远高于其携带质粒的多样性。在7例患者中观察到了携带的质粒跨不同菌种传播的现象，这提示当前基于菌株的耐药监测策略可能低估了耐药基因跨物种传播的风险。