Martinez Marilyn, Silley Peter
Office of New Animal Drug Evaluation (HFV-130), Center for Veterinary Medicine Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA.
Handb Exp Pharmacol. 2010(199):227-64. doi: 10.1007/978-3-642-10324-7_10.
This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed.
本章概述了我们目前对抗菌药物耐药性产生机制的理解、耐药性定义的国际差异、追踪药物敏感性变化的持续努力，以及可能影响治疗干预选择的因素。后者呈现出一个复杂变量矩阵，包括药物作用机制、抗菌药物在目标患者群体中的药代动力学（PK）、细菌对抗菌药物反应的药效动力学（PD）、将影响剂量选择的PK/PD关系，以及宿主免疫系统的完整性。最后，探讨了细菌耐受性和细菌耐药性之间的差异，以及非传统抗感染治疗的潜力。
