泛耐药鲍曼不动杆菌LPS脂质A基因突变介导多黏菌素耐药及治疗方案调整

  目的  探讨泛耐药鲍曼不动杆菌（XDRAB）脂多糖（LPS）脂质A生物合成基因lpx A、lpx C、lpx D突变对多黏菌素耐药的意义，并筛选合适的联合治疗方案。  方法  选择近两年患者呼吸道分泌物中的72株XDRAB为研究对象。根据XDRAB菌株对多黏菌素的最小抑菌浓度（MIC）分别将其纳入耐药组和敏感组；PCR扩增lpx A、lpx C、lpx D基因序列，分析突变情况，比较耐药组和敏感组突变率；采用微量棋盘稀释法评价联合用药药效，分为多黏菌素+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、多黏菌素+磷霉素组。计算联合用药方案部分抑菌（FIC）指数，比较表现协同、相加、无关、拮抗作用的菌株百分比。  结果  获得XDRAB菌株共72株，其中耐药组共21株，占29.17%，敏感组共51株，占70.83%；部分菌株存在lpx A、lpx C、lpx D基因突变；耐药组基因突变率为90.48%，高于敏感组的11.76%，差异有统计学意义（P<0.05）。联合药敏实验结果显示，多黏菌素+亚胺培南组协同作用百分比高于多黏菌素+磷霉素组，无关作用百分比低于多黏菌素+磷霉素组（P<0.01）。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+左氧氟沙星组协同作用及无关作用百分比比较，差异无统计学意义（P>0.05）。  结论  XDRAB对多黏菌素存在耐药现象，与lpx A、lpx C、lpx D突变有关，临床治疗推荐多黏菌素+亚胺培南等联合用药方案，以减少耐药菌二次感染。

Significance of Lipopolysaccharide Lipid A Gene Mutation of Extensively Drug-resistant Acinetobacter baumanii on Polymyxin Resistance and Its Influence on Treatment

  Objective  To explore the significance of the resistance to polymyxin resistance of the extensively drug resistant Acinetobacter baumannii (XDRAB) lipopolysaccharide (LPS) lpx A, lpx C, lpx D 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 lpx A, lpx C, lpx D 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 lpx A, lpx C, lpx D 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 (P<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 (P<0.01).  Conclusion  XDRAB is resistant to polymyxin, which is related to mutations in LPS lipid A biosynthesis genes lpx A, lpx C, lpx D. Clinical treatment should adopt a combination of polymyxin+imipenem/meropenem and other drug combination to reduce the secondary infection of drug resistant bacteria.