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[广泛耐药菌脂多糖脂质A基因突变对多黏菌素耐药性的意义及其对治疗的影响]

[Significance of Lipopolysaccharide Lipid A Gene Mutation of Extensively Drug-resistant on Polymyxin Resistance and Its Influence on Treatment].

作者信息

Mao Hong-Bin, He Ming, He Su-Na

机构信息

Department of Clinical Pharmacy, Kaifeng People's Hospital, Kaifeng 475000, China.

Department of Clinical Pharmacy, the First Affiliated Hospital of Henan University, Kaifeng 475001, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Jan;52(1):124-128. doi: 10.12182/20210160208.

Abstract

OBJECTIVE

To explore the significance of the resistance to polymyxin resistance of the extensively drug resistant (XDRAB) lipopolysaccharide (LPS) , , and to screen appropriate combination therapy.

METHODS

In the past two years, 72 XDRAB in the secretions of our patients were selected as the research object. According to the minimum inhibitory concentration (MIC) of the XDRAB strain on polymyxin, they were included in the drug resistance group and the sensitive group. The gene sequences of strains , , were compared with the standard strains to analyze gene mutations and compared the mutation rates in the drug resistant group and the sensitive group. The efficacy of the combination drugs was evaluated by microcheckerboard dilution method, including polymyxin+imipenem group, polymyxin+meropenem group, polymyxin+cefoperazone/sulbactam group, polymyxin+levofloxacin group, and polymyxin+fosfomycin group. Calculated the fractional inhibitory concentration (FIC) index of the combined medication regimen and compared the percentage of strains that exhibited synergistic, additive, irrelevant, and antagonistic effects.

RESULTS

Tentyone were in the drug resistant group, accounting for 21 (29.17%,) and 51 were in the sensitive group, accounting for 70.83%. Some strains had mutations in , , genes. The mutation rate in the drug resistant group was 90.48%, which was significantly higher than 11.76% in the sensitive group, the difference was statistically significant ( <0.05). The combined drug sensitivity test showed, compared with the polymyxin+fosfomycin group, the mycotin+fosfomycin group had a higher percentage of strains with synergistic FIC index in the polymyxin+imipenem group, the difference was statistically significant ( <0.01).

CONCLUSION

XDRAB is resistant to polymyxin, which is related to mutations in LPS lipid A biosynthesis genes , , . Clinical treatment should adopt a combination of polymyxin+imipenem/meropenem and other drug combination to reduce the secondary infection of drug resistant bacteria.

摘要

目的

探讨广泛耐药鲍曼不动杆菌(XDRAB)脂多糖(LPS)对多黏菌素耐药的意义,并筛选合适的联合治疗方案。

方法

选取近两年本院患者分泌物中的72株XDRAB作为研究对象。根据XDRAB菌株对多黏菌素的最低抑菌浓度(MIC),将其分为耐药组和敏感组。将菌株的基因序列与标准菌株进行比较,分析基因突变情况,并比较耐药组和敏感组的突变率。采用微量棋盘稀释法评估联合用药的疗效,包括多黏菌素+亚胺培南组、多黏菌素+美罗培南组、多黏菌素+头孢哌酮/舒巴坦组、多黏菌素+左氧氟沙星组和多黏菌素+磷霉素组。计算联合用药方案的部分抑菌浓度(FIC)指数,比较呈现协同、相加、无关和拮抗作用的菌株百分比。

结果

耐药组21株,占21(29.17%),敏感组51株,占70.83%。部分菌株在、、基因发生突变。耐药组的突变率为90.48%,显著高于敏感组的11.76%,差异有统计学意义(<0.05)。联合药敏试验显示,与多黏菌素+磷霉素组相比,多黏菌素+亚胺培南组中FIC指数呈协同的菌株百分比更高,差异有统计学意义(<0.01)。

结论

XDRAB对多黏菌素耐药,这与LPS脂质A生物合成基因、、的突变有关。临床治疗应采用多黏菌素+亚胺培南/美罗培南等联合用药方案,以减少耐药菌的继发感染。

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