在产生VIM的PBP-3定向治疗中,Pseudomonas aeruginosa产生了细菌转换器,在伪装中持续存在
Nicholas M Smith1, Katie Rose Boissonneault1, Patricia N Holden1
1Division of Clinical and Translational Therapeutics, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
International journal of antimicrobial agents
|June 30, 2024
概括
产生金属β-乳糖酶 (MBL) 的Pseudomonas aeruginosa是一种公共卫生威胁,可以转化为持久形式. 基于阿兹特雷的疗法减少了细菌的数量,但在停止治疗后,P. aeruginosa迅速恢复到杆状.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 产生金属β-乳糖酶 (MBL) 的Pseudomonas aeruginosa对公众健康构成重大风险.
- 这种病原体表现出表型可塑性,导致抗生素有效性降低.
研究的目的:
- 量化阿兹特雷诺姆基疗法对产生VIM-2的P. aeruginosa的杀死效果.
- 为了记录P. aeruginosa的形态变化,促进持久性.
主要方法:
- 在9天内使用空洞纤维感染模型 (HFIM) 与产生VIM-2的P. aeruginosa.
- 测试了各种治疗手臂,包括阿兹特雷诺姆,塞夫塔齐迪姆/阿维巴克坦,波利米克辛B和组合.
- 采用实时成像来观察持续的细胞逆转.
主要成果:
- 观察到光密度和细菌数量之间的差异,表明表型变化.
- 阿兹特雷南单一治疗导致120小时后的CFU/mL为0,但仍然存在显著的OD计数差异.
- 在停止治疗后,P. aeruginosa在2小时内迅速从丝状转变为杆状.
结论:
- 有效管理生产MBL的P. aeruginosa需要一个全面的战略.
- 这一战略必须优先考虑最大限度地杀死细菌,并最大限度地减少耐药,持久的亚群.
- 消除药物诱导的表型变形体对于成功治疗至关重要.
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