环丙沙星耐药的铜绿假单胞菌临床特征及耐药机制

Clinical characteristics and resistance mechanism of ciprofloxacin-resistant Pseudomonas aeruginosa

目的了解新疆阿克苏地区临床分离的环丙沙星耐药的铜绿假单胞菌感染临床特征,临床常见抗生素的耐药情况,初步探讨环丙沙星耐药的铜绿假单胞菌耐药机制。方法收集2017年1月至2018年4月在新疆生产建设兵团第一师医院临床分离的标本,按照法国梅里埃微生物鉴定分析系统操作规范进行菌种鉴定,对环丙沙星耐药的铜绿假单胞菌行药敏分析,分析其临床特点、临床常用抗生素的耐药情况,运用PCR的方法扩增环丙沙星耐药的铜绿假单胞菌的gyrA、gyrB、parC、parE基因,对各基因的产物进行测序以明确基因的突变情况。结果共收集14株临床环丙沙星耐药的铜绿假单胞菌,痰标本为主,主要来自ICU、呼吸科。分离出环丙沙星耐药铜绿假单胞菌的患者平均年龄(63.07±21.71)岁,平均住院日最短5 d,最长276 d,中位数162 d,死亡率为21.43%。对临床常用的抗生素哌拉西林/舒巴坦、妥布霉素、阿米卡星、头孢他啶、头孢吡肟、庆大霉素、亚胺培南、美罗培南敏感,对复方新诺明、头孢曲松、头孢呋辛、头孢唑啉、氨苄西林耐药。7株为多重耐药株。14株菌株中7株gyrA基因发生Thr83→Ile,2株中gyrB基因发生Ser466→Phe,1株parC基因发生Glu91→Lys,没有parE基因发生氨基酸的改变。结论环丙沙星耐药的铜绿假单胞菌感染患者住院日长,病死率高。我院铜绿假单胞菌对环丙沙星耐药的主要耐药机制是铜绿假单胞菌染色体DNA的gyrA基因第83位密码子突变。

Objective To understand the clinical characteristics of ciprofloxacin-resistant Pseudomonas aeruginosa infection in Aksu, Xinjiang, and the resistance of commonly used antibiotics, and to explore the resistance mechanism of ciprofloxacin-resistant Pseudomonas aeruginosa. Methods Clinical isolates from Xinjiang Production and Construction Corps First Division Hospital from January 2017 to April 2018 were collected and identified by VITEK2 compact automatic microbial analysis system. Drug sensitivity of ciprofloxacin-resistant Pseudomonas aeruginosa was analyzed, and its clinical characteristics and drug resistance to commonly used antibiotics were analyzed. The gyrA, gyrB,parC and parE genes of Pseudomonas aeruginosa were amplified by PCR and then sequenced to identify the mutation of the genes. Results A total of 14 strains of ciprofloxacin-resistant Pseudomonas aeruginosa were collected, mainly from sputum samples from Intensive Care Unit(ICU) and Respiratory Department. The average age of the patients with ciprofloxacin-resistant Pseudomonas aeruginosa isolates was(63.07±21.71) years, the average hospitalization duration lasted from 5 days to 276 days(with a median of 162 days), and the mortality rate was 21.43%.Antibiotic-susceptibility tests showed that most ciprofloxacin-resistant Pseudomonas aeruginosa were sensitive to piperacillin/sulbactam, tobumycin,amicacin, ceftazidime, cefpime, gentamicin, imipenem, meropenem, and resistant to compound neotamine, ceftriaxone,cefuroxime, cefazolin and ampicillin. Seven of the strains were multidrug resistant. Further analysis revealed that the resistant strains had mutation in gyrA(Thr83→Ile) of 7 strains, in gyrB(Ser466→Phe) of 2 cases, and in parC(Glu91→Lys) of 1 case, with no mutation detected in parE gene. Conclusion Ciprofloxacin-resistance Pseudomonas aeruginosa infections is related to long hospitalization duration and high mortality. The main mechanism of its resistance to ciprofloxacin is the mutation of codon 83 of gyrA gene in chromosomal DNA of Pseudomonas aeruginosa.