医院获得性肺炎的铜绿假单胞菌QRDR基因突变分析

QRDR Mutations in Fluoroquinolon-Resistant Pseudomonas aeruginosa and Its Relationship with the Usage of Antibiotics in Nosocomial Pneumonia

目的探讨医院获得性肺炎的铜绿假单胞菌氟喹诺酮耐药决定域(QRDR)基因突变及其与临床用药的关系。方法对2006年1月至2007年12月上海交通大学医学院附属新华医院医院获得性肺炎患者痰中分离得到的铜绿假单胞菌84株,采用限制性长度多态性分析(RFLP)结合基因测序检测所得菌株QRDR的基因突变,并结合临床用药情况进行分析。结果50株耐药菌经检测发现QRDR区存在突变42株,占84.0%。GyrBSer464发生突变34株,占68.0%。GyrBSer464突变组与非突变组比较,对应的患者分离菌株之前使用β-内酰胺类的情况存在差异(OR=11.3,P=0.003及OR=3.5,P=0.023)。喹诺酮类药物在采集前30d内的使用时间也存在差异(P=0.038)。结论铜绿假单胞菌对喹诺酮的耐药性与QRDR区突变的发生相一致,耐药菌株突变类型以GyrBSer464突变为主,可能与喹诺酮类和β-内酰胺类的使用有关。

Objective To investigate the mutations of quinolone resistance determinational region （QRDR） in fluoroquinolon-resistant Pseudomonas aeruginosa strains isolated from patients with nosocomial pneumonia. Methods Eight-four Pseudomonas aeruginosa strains isolated from patients with nosocomial pneumonia in Xinhua Hospital during January 2006 to December 2007, from whom fluoroquinolon-resistant resisitant （case） and fluoroquinolon-susceptible （control） Pseudomona aeruginosa were identified. The mutation of QRDR was tested by restriction fragment length polymorphism （RFLP） and gene sequencing. The relationship between QRDR mutations and clinical prescription was analyzed. Results Mutation in QRDR was found in 42 isolates among the 50 fluoroquinlon-resisitant isolates （ 84.0% ） , while no mutation was found in fluoroquinlon-susceptible isolates. The mutation in GyrB Ser464 was found in 34 isolates （68.0%）. There was statistical difference in the usage of β-lactams between the GyrB-Ser464-mutated group and the non-GyrB-Ser464-mutated group （ OR = 11.3, P = 0. 003 and OR = 3.5, P = 0. 023 ） , also in the time of fluoroquinolon usage before isolated （ P = 0. 038 ）. Conclusions The mutation of QRDR is contributing to fluoroquindor-resisitance of Pseudomona aeruginosa, most of which lies in GyrB Ser464. Abuse of β-lactams and fluoroquinolon may be the risk factors of mutation in GyrB Ser464.