Fursova Nadezhda K, Astashkin Eugeny I, Knyazeva Anastasia I, Kartsev Nikolay N, Leonova Ekaterina S, Ershova Olga N, Alexandrova Irina A, Kurdyumova Natalia V, Sazikina Svetlana Yu, Volozhantsev Nikolay V, Svetoch Edward A, Dyatlov Ivan A
State Research Center for Applied Microbiology and Biotechnology, Obolensk, 142279, Moscow Region, Russia.
The Burdenko Neurosurgery Institute, Moscow, 125047, Russia.
Ann Clin Microbiol Antimicrob. 2015 Nov 2;14:46. doi: 10.1186/s12941-015-0108-y.
The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a great problem of healthcare worldwide. Study of the spread for bla OXA-48-like genes coding epidemically significant carbapenemases among hospital pathogens is important for the regional and global epidemiology of antimicrobial resistance.
Antibacterial resistant isolates of Klebsiella pneumoniae (n = 95) from 54 patients, P. mirabilis (n = 32) from 20 patients, Enterobacter aerogenes (n = 6) from four patients, and Enterobacter cloacae (n = 4) from four patients were collected from January, 2013 to October, 2014 in neurosurgical intensive care unit (ICU) of the Burdenko Neurosurgery Institute, Moscow. Characteristics of the isolates were done using susceptibility tests, PCR detection of the resistance genes, genotyping, conjugation, DNA sequencing, and bioinformatic analysis.
Major strains under study were multi drug resistant (MDR), resistant to three or more functional classes of drugs simultaneously-98.9 % K. pneumoniae, 100 % P. mirabilis, one E. aerogenes isolate, and one E. cloacae isolate. Molecular-genetic mechanism of MDR in K. pneumoniae and P. mirabilis isolates were based on carrying of epidemic extended-spectrum beta-lactamase bla CTX-M-15 gene (87.2 and 90.6 % accordingly), carbapenemase bla OXA-48-like gene (55.3 and 23.3 % accordingly), and class 1 (54.8 and 31.3 % accordingly) and class 2 (90.6 % P. mirabilis) integrons. The bla OXA-48-like-positive K. pneumoniae were collected during whole two-year surveillance period, while P. mirabilis and Enterobacter spp. carrying bla OXA-48-like genes were detected only after four and 18 months after the research start, respectively. The bla OXA-48-like gene acquisition was shown for P. mirabilis isolates collected from five patients and for E. cloacae isolate collected from one patient during their stay in the ICU, presumably from bla OXA-48-like-positive K. pneumoniae. The source of the bla OXA-244 gene acquired by E. aerogenes isolates and the time of this event were not recognized.
The expanding of CPE in the surveyed ICU was associated with the spread of bla OXA-48 and bla OXA-244 carbapenemase genes documented not only among K. pneumoniae, well-known bacterial host for such genes, but among P. mirabilis, E. aerogenes, and E. cloacae.
产碳青霉烯酶肠杆菌科细菌（CPE）的传播是全球医疗保健领域的一个重大问题。研究医院病原体中编码具有重要流行病学意义的碳青霉烯酶的bla OXA-48样基因的传播情况，对于区域和全球抗菌药物耐药性流行病学研究具有重要意义。
2013年1月至2014年10月期间，从莫斯科布尔坚科神经外科研究所神经外科重症监护病房（ICU）收集了54例患者的肺炎克雷伯菌抗菌药物耐药分离株（n = 95）、20例患者的奇异变形杆菌（n = 32）、4例患者的产气肠杆菌（n = 6）和4例患者的阴沟肠杆菌（n = 4）。通过药敏试验、耐药基因的PCR检测、基因分型、接合试验、DNA测序和生物信息学分析对分离株进行特征分析。
主要研究菌株为多重耐药（MDR），同时对三类或更多功能类别的药物耐药——98.9%的肺炎克雷伯菌、100%的奇异变形杆菌、1株产气肠杆菌分离株和1株阴沟肠杆菌分离株。肺炎克雷伯菌和奇异变形杆菌分离株中MDR的分子遗传机制基于携带流行的超广谱β-内酰胺酶bla CTX-M-15基因（分别为87.2%和90.6%）、碳青霉烯酶bla OXA-48样基因（分别为55.3%和23.3%）以及1类（分别为54.8%和31.3%）和2类（奇异变形杆菌为90.6%）整合子。bla OXA-48样阳性的肺炎克雷伯菌是在整个两年监测期内收集到的，而携带bla OXA-48样基因的奇异变形杆菌和肠杆菌属分别在研究开始后的4个月和18个月才被检测到。在5例患者的奇异变形杆菌分离株和1例患者的阴沟肠杆菌分离株入住ICU期间，显示获得了bla OXA-48样基因，推测来自bla OXA-48样阳性的肺炎克雷伯菌。未明确产气肠杆菌分离株获得bla OXA-244基因的来源及该事件发生的时间。
在所调查的ICU中，CPE的传播与bla OXA-48和bla OXA-244碳青霉烯酶基因的传播有关，这些基因不仅在肺炎克雷伯菌（此类基因常见的细菌宿主）中存在，在奇异变形杆菌、产气肠杆菌和阴沟肠杆菌中也有发现。
