鲍曼不动杆菌对替加环素的耐药性及其稳定性研究

Resistance of Acinetobacter baumannii to Tigecycline

目的了解长期抗菌药物压力及常用紫外线消毒对鲍曼不动杆菌耐药性的影响及替加环素(TGC)耐药鲍曼不动杆菌耐药性在群体中存续的能力。方法选取临床分离TGC敏感鲍曼不动杆菌3株,分别采用多步法及紫外线照射体外诱导耐药,微量肉汤稀释法检测诱导前后鲍曼不动杆菌对TGC的最低抑菌浓度(MIC)变化。选取临床分离TGC耐药鲍曼不动杆菌2株,在空白MHA平板中反复传代,测定其MIC值。最后选取TGC敏感株及TGC诱导同源耐药株进行TGC耐药株适应度代价研究。结果应用多步法成功诱导出TGC耐药株;紫外线照射虽然对TGC耐药性未发生影响,但其MIC值有上升趋势。TGC耐药鲍曼不动杆菌传代40代后菌株MIC值无明显变化。TGC敏感株及TGC诱导同源耐药株进行相同条件下培养,体外单独培养时耐药株达到对数生长期及平台期的时间均较敏感株长;混合培养时,随着连续传代,耐药株菌落数量较敏感株迅速减少,甚至耐药株被清除。结论 TGC可诱导鲍曼不动杆菌产生获得性耐药。鲍曼不动杆菌对TGC的耐药可能具有遗传稳定性。TGC耐药株较敏感株适应性下降。

Objective To determine the impact of long-term use of antibiotics and ultraviolet radiation on the resistance of Acinetobacter baumannii to tigecycline and the viability of tigecycline-resistant Acinetobacter baumannii . Methods Three strains of tigecycline sensitive Acinetobacter baumannii were selected. Tigecycline resistance was induced through multi-step method or by ultraviolet radiation. Two strains of tigecycline resistant Acinetobacter baumannii were repeatedly passaged on blank MHA plates, for the purpose of determination of minimum inhibitory concentrations （MICs） of tigecycline using broth microdilution method. The tigecycline sensitive （b38） and homologous resistant Acinetobacter baumannii （b38′） were cultured separately and conjointly to evaluate its fitness costs of tigecycline resistance. Results Tigecycline resistant strains were successfully induced using multi-step method. Ultraviolet radiation did not change the sensitivity of the three strains to tigecycline, but elevated the MICs of tigecycline. The MICs of tigecycline did not change over 40 generations. It took much more time for the resistant strains to reach logarithmic growth phase and plateau phase compared with the tigecycline sensitive strains. With repeated passage, the tigecycline resistant strains decreased rapidly, even vanished in conjointly culture. Conclusion Acinetobacter baumannii can acquire tigecycline resistance. The resistance may have genetic stability. The resistant strains have less adaptability than the sensitive strains.