Tam Vincent H, Schilling Amy N, Melnick David A, Coyle Elizabeth A
Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX 77030, USA.
Diagn Microbiol Infect Dis. 2005 Jun;52(2):145-51. doi: 10.1016/j.diagmicrobio.2005.02.010.
Suppression of resistance in a dense population of Pseudomonas aeruginosa has been shown with optimized quinolone exposures. However, relevance to the beta-lactams is questionable because of the unknown impact of the inoculum effect. We explored the bactericidal activity of various beta-lactams and their propensity to suppress spontaneous resistance. Minimal killing and resistance selection was seen with piperacillin, most likely due to the inoculum effect. Moderate and significant killing was seen at 24 h with ceftazidime and meropenem, respectively; however, regrowth and selective resistance amplification was apparent at 48 h. Our results suggest that different beta-lactam subclasses have a distinct killing profile and propensity to suppress resistance against a dense population of P. aeruginosa. The pharmacodynamics of each subclass of agent should be examined individually, and investigations longer than 24 h may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression.
已表明在优化喹诺酮暴露条件下，可抑制高密度铜绿假单胞菌群体中的耐药性。然而，由于接种物效应的影响未知，其与β-内酰胺类药物的相关性存在疑问。我们探究了各种β-内酰胺类药物的杀菌活性及其抑制自发耐药性的倾向。哌拉西林的杀菌和耐药性选择作用最小，这很可能是由于接种物效应。头孢他啶和美罗培南分别在24小时时出现中度和显著杀菌作用；然而，在48小时时明显出现再生长和选择性耐药性扩增。我们的结果表明，不同的β-内酰胺类亚类具有独特的杀菌模式和抑制针对高密度铜绿假单胞菌群体耐药性的倾向。每种药物亚类的药效学应单独进行研究，可能需要超过24小时的研究来全面评估药物暴露与耐药性抑制可能性之间的关系。
