Program in Pathobiology, Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, China.
Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
Clin Infect Dis. 2018 Feb 10;66(5):676-685. doi: 10.1093/cid/cix885.
mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1-positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1-positive 3GC-R strains.
Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized.
Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1-positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1-positive 3GC-R Enterobacteriaceae (P < .001). mcr-1-positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1-positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1-associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs.
The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.
肠杆菌科中 mcr-1 介导的粘菌素耐药性令人担忧，因为粘菌素被用于治疗多药耐药肠杆菌科感染。我们在中国广州鉴定了人类粪便 mcr-1 阳性率和 mcr-1 阳性、第三代头孢菌素耐药（3GC-R）肠杆菌科定植的趋势，并研究了 mcr-1 阳性 3GC-R 菌株中 mcr-1 的遗传背景。
收集 3 家医院（2011-2016 年）住院和门诊患者的粪便标本。使用迭代顺序回归评估 mcr-1 携带趋势。对 mcr-1 阳性分离株的亚群进行测序（全基因组测序[WGS]，Illumina），并对 mcr-1 的遗传背景（侧翼区，质粒）进行分析。
共收集 8022 份粪便标本，497 份（6.2%）为 mcr-1 阳性，182 份（2.3%）携带 mcr-1 阳性 3GC-R 肠杆菌科。我们观察到 mcr-1（0%[2011 年 4 月]至 31%[2016 年 3 月]）和最近（自 2014 年 1 月以来；0%[2011 年 4 月]至 15%[2016 年 3 月]）人类携带 mcr-1 阳性 3GC-R 肠杆菌科的显著增加（P <.001）。mcr-1 阳性 3GC-R 分离株通常为多药耐药。对 mcr-1 阳性 3GC-R 分离株（70 株大肠埃希菌，3 株肺炎克雷伯菌）进行 WGS 显示细菌株多样性；mcr-1 与常见质粒骨架（IncI、IncHI2/HI2A、IncX4）相关，有时与多个质粒相关；mcr-1 染色体整合频繁；mcr-1 相关插入序列 ISApl1 的高迁移率。序列数据与动物/人类宿主之间的质粒传播一致。
mcr-1 广泛存在于多药耐药性大肠埃希菌中，对人类定植构成临床威胁；不同的遗传机制（菌株/质粒/插入序列）促进了 mcr-1 的传播，并将促进其持续存在。
