喹诺酮类耐药福氏志贺菌的质粒介导耐药机制研究

Research on resistant mechanism of plasmid-mediated in quinolone-resistant Shigella flexneri

目的研究萘啶酸耐药的福氏志贺菌中质粒介导的喹诺酮类耐药基因qnrA、qnrB、qnrS、qepA、aac(6')-Ib-cr的流行状况。方法收集我院2002-2011年腹泻患者大便标本分离出的福氏志贺菌,用纸片扩散法测定13种抗菌药物的敏感性,筛选出存活的82株萘啶酸耐药的野生株。采用PCR方法检测菌株的qnrA、qnrB、qnrS、qepA、aac(6')-Ib-cr耐药基因,对PCR阳性产物进行测序确定基因型别。结果 82株萘啶酸耐药的福氏志贺株以F2a最为常见,占47.56%,对其他多种抗生素存在耐药,耐药率分别为氨苄西林95.12%、哌拉西林18.29%、头孢噻肟12.20%、头孢曲松12.20%、头孢吡肟7.50%、环丙沙星53.66%、氧氟沙星37.80%、诺氟沙星36.59%、左氧氟沙星26.83%、头孢美唑4.00%、氯霉素40.24%、复方磺胺甲恶唑77.50%和磷霉素6.10%。共检测到质粒介导耐药基因的细菌13株(15.85%),3株携带qnrB基因均为qnrB6型;8株携带qnrS基因均为qnrS1型;7株携带aac(6')-Ib-cr基因,其中有5株同时携带qnrB和aac(6')-Ib-cr。结论本地区福氏志贺菌临床分离株对喹诺酮类抗菌药物耐药较严重,存在质粒介导的耐药机制,应加强监测。

Objective To study the prevalence of resistant gene including qnrA, qnrB, qnrS, qepA, aac（σ）- Ib-cr in Shigella flexneri resistant to nalidixic acid. Methods Collecting the Shigella flexneri isolated from stool specimens of diarrhea patients during 2002--2011 in our hospital and Screening 82 wild strains resistant to nalidixic acid by using K-B method. Furthermore, the susceptibility of 13 antimicrobial agents of Shigella flexneri were tested and resistant gene including qnrA, qnrB, qnrS, qepA, aac（σ）-Ib-cr was detected by PCR. Results Among 82 resistant-nalidixic acid Shigellaflexneri, F2a is the dominant serotype and account for 47.56%. The resistant rate of resistant-nalidixic acid Shigella flexneri to other antibiotics was 95.12% in ampicillin, 18.29% in piperacillin, 12.20% in cefotaxime or ceftriaxone, 7.50% in cefepime, 53.66% in ciprofloxacin, 37.80% in ofloxacin, 26.83% in levofloxacin, 36.59% in norfloxacin,4% in Cefmetazole, 40.24% in chloramphenicol, 77.50% in sulfamethoxazole and 6.10% in fosfomycin respectively. All 13（15.85%） plasmid-mediated resistant gene including qnrB （type 6） 3 strains, qnrS （qnrS type 1） 8 strains and aac（σ）-Ib-cr 7 strains were detected in these organisms. Among them, 5 isolates carried both resistant gene qnrB and aac（6＇）-Ib-cr. Nor qnrA or qepA resistant gene was positive. Conclusion The resistance of Shigellaflexneri to quinolones is serious in our region. There are plasmid-mediated quinolone-resistance gene in Shigella flexneri isolated from clinical samples. Monitoring the resistance and resistant mechanism of Shigella flexneri should be strengthened.