6株携带blaIMP-4基因耐碳青霉烯香坊肠杆菌耐药性研究

Study on drug resistance of six carbapenem-resistant Enterobacter xiangfangensis strains carrying blaIMP-4 gene

目的探讨新生儿重症监护病房中香坊肠杆菌(Enterobacter xiangfangensis,E.xiangfangensis)耐药特点。方法收集2019年12月至2020年2月间新生儿重症监护病房分离的6株E.xiangfangensis,采用肉汤稀释法和纸片扩散法检测其耐药性,采用illuminanovaseq 6000150 bp多长双末端测序测略进行全基因组测序,检测其耐药基因,同时收集耐药菌株感染患儿的临床资料。结果6株E.xiangfangensis来自5例早产儿,其中1例为痰培养阳性,考虑为定植,其余4例均为败血症,4例败血症患儿均具有感染的高危因素,1例早产儿住院期间出现2次E.xiangfangensis败血症。药敏试验6株E.xiangfangensis对替加环素、阿米卡星、复方新诺明均敏感,1株对环丙沙星敏感,5株对哌拉西林他唑巴坦敏感,4株对头孢哌酮钠舒巴坦敏感,2株对米诺环素敏感,所有菌株均对美罗培南等碳青霉烯类药物耐药或中介。耐药基因检测6株均携带β-内酰胺类耐药基因blaIMP-4、laACT-55、喹诺酮类耐药基因qnrS 1,5株携带氨基糖苷类耐药基因aac(6')-Ib4,5株同时携带喹诺酮类耐药基因qnrS 1和磺胺类耐药基因sul 1,5株同时携带喹诺酮类耐药基因oqxA 9和oqxB 9。多位点序列分型提示6株E.xiangfangensis序列型均为148型。结论E.xiangfangensis对碳青霉烯类药物耐药不一定是耐碳青霉烯药物基因表达引起,需根据细菌的耐药特点合理选择抗生素,减少耐药菌的产生,而不是优先选择碳青霉烯类抗生素。

Objective To explore the drug resistance characteristics of Enterobacter xiangfangensis(E.xiangfangensis)infection in neonatal intensive care unit.Methods Six strains of E.xiangfangensis were isolated from newborns in neonatal intensive care unit from December 2019 to February 2020.These strains were tested for drug resistance using both broth dilution method and disc diffusion method,and 150bp multiple insert size paired-end sequencing was performed using the Illuminanovaseq 6000 to detect drug resistant genes.Meanwhile,clinical data of the children infected with the drug-resistant strains were collected.Results Six strains of E.xiangfangensis were derived from 5 premature infants.One of them was positive in sputum culture,which was considered as colonization.The other 4 infants were sepsis,and 4 cases of sepsis had high risk factors for infection.A premature infant experienced E.xiangfangensis septicemia twice during hospitalization.Drug susceptibility test showed that 6 strains of E.xiangfangensis were sensitive to tigacycline,amikacin and cotrimoxazole.Sensitivity to ciprofloxacin was observed in 1 strain,sensitivity to piperacillin tazobactam was observed in 5 strains,sensitivity to cefoperazone sodium sulbactam was observed in 4 strains,and sensitivity to minocycline was observed in 2 strains.All strains were resistant or intermediate to carbapenems such as meropenem.Identification of the drug resistant genes showed thatβ-lactam resistance genes blaIMP-4 or laACT-55 and quinolone resistance gene qnrS 1 were identified in all 6 strains,aminoglycoside resistance gene aac(6')-Ib4 was found in 5 strains,quinolone resistance gene qnrS 1 and sulfonamide resistance gene sul 1 coexisted in 5 strains,quinolone resistance genes oqxA 9 or oqxB9 also coexisted in 5 strains.Multilocus sequence typing showed that all the 6 strains of E.xiangfangensis had the same sequence type of 148.Conclusions E.xiangfangensis resistance to carbapenems may not be caused by the expression of carbapenem-resistant genes.Antibiotics should be selected reasonably according to the characteristics of bacterial resistance to reduce the generations of resistant bacteria,rather than blindly selecting the carbapenem antibiotics.