临床株鲍曼不动杆菌gyrA和parC突变与氟喹诺酮的耐药性及其突变风险因素分析

Risk Factors for gyrA and parC Mutations and Analysis of the Correlation between Quinolone Resistance and gyrA and parC Mutations in Clinical Isolates of Acinetobacter Baumannii

目的:探讨gyrA和parC基因突变在本机构临床分离株鲍曼不动杆菌(Acinetobacter baumannii,AB)的流行情况,分析其与氟喹诺酮类药物耐药的相关性,并明确AB菌gyrA和parC基因突变的风险因素。方法:收集龙岩第一医院2017年9月-2018年12月期间住院的下呼吸道AB菌感染住院病人39例,分离并培养AB菌,E-test方法检测各菌株的左氧氟沙星和环丙沙星敏感性。PCR和直接测序法检测AB菌的gyrA和parC基因突变。结果:39株临床株AB菌中,22株(56.4%)发生了gyrA和parC双基因突变,3株(7.7%)存在gyrA单基因突变,2株(5.1%)存在parC单基因突变;且gyrA和parC双基因突变株左氧氟沙星MIC≥64,环丙沙星MIC≥16,gyrA或parC单基因突变左氧氟沙星MIC≥8,环丙沙星MIC≥2。携带gyrA和parC突变AB菌组病人较携带无突变组病人住院时间长(P<0.05),且呼吸机、气管插管、血液制品及抗生素的使用率更高(P<0.05);其中抗生素的使用率作为gyrA和parC突变独立风险因素存在(P<0.05)。结论:gyrA和parC基因双突变株是本机构AB菌对左氧氟沙星和环丙沙星耐药的主要流行株,亦是其对左氧氟沙星和环丙沙星高浓度耐药的主要原因,住院抗生素的使用率是AB菌gyrA和parC突变的独立风险因素。

Objective:To explore the prevalence state of the gyrA and parC mutations of Acinetobacter baumannii clinical isolates in this institution,to analyze the the correlation between the gyrA and parC mutations and fluoroquinolone resistance,and to definite the risk factors for gyrA and parC mutations in A.baumannii wild strains and mutant strains.Methods:A retrospective study of 39 lower respiratory tract A.baumannii-infected cases,identified in Fujian Longyan first hospital from September 2017 to December 2018 was conducted,isolation and culture the A.baumannii,levofloxacin and ciprofloxacin’s sensitibility test of 39 A.baumannii was determined by microdilution quantitative minimum inhibitory concentration(MIC)method.And PCR and sequencing were performed for detection of mutation in gyrA and parC genes.Results:Of 39 isolates,22 isolates(56.4%)with the double mutations in gyrA and parC were resistant to levofloxacin with a MIC of≥64μg/ml and ciprofloxacin with a MIC≥16μg/ml;3(7.7%)isolates had one mutation in gyrA,2(5.1%)isolates had one mutation in parC,one mutation in gyrA or parC were resistant to levofloxacin with a MIC of≥8μg/ml and ciprofloxacin with a MIC≥2μg/ml,mutations of the gyrA and parC in A.baumannii may be associated with length of hospital stay,ventilator use,endotracheal intubation,infusion of blood products,and the use of antibiotics(P<0.05),and the use of antibiotics is the independent risk factors(P<0.05).Conclusion:Isolates with double mutations of gyrA and parC genes is the major epidemic strains in this institution which was resistant to levofloxacin and ciprofloxacin,and which also associated with higher level resistance of levofloxacin and ciprofloxacin.And the use of antibiotics is the independent risk factors.