Restricting the selection of antibiotic-resistant mutants: A general strategy derived from fluoroquinolone studies
Restricting the selection of antibiotic-resistant mutants: A general strategy derived from fluoroquinolone studies
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DOI：
10.1086/321841
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发表时间：
2001-09-15
影响因子：
11.8
通讯作者：
Drlica, K
中科院分区：
文献类型：
--
作者：
Zhao, XL;Drlica, K
对氟喹诺酮类药物的研究已经产生了一种限制选择耐药性突变体的通用方法。该策略基于使用需要细胞获得2个并发耐药突变以进行生长的抗生素浓度。该浓度被称为“突变预防浓度”（MPC），因为即使当接种>10（10）个细胞时也没有回收抗性菌落。抗性突变体仅在从生长抑制开始的点（近似为最小抑制浓度）延伸至MPC的浓度范围（突变体选择窗口）内选择。突变体选择窗口的尺寸可以以多种方式减小，包括调整抗生素结构和剂量方案。如果大于或等于2种抗菌药物的标准化药代动力学曲线超过抑制生长的浓度，则可以关闭窗口以防止通过联合治疗进行突变体选择。这些原则的应用可以大大限制耐药病原体的选择。
Studies with fluoroquinolones have led to a general method for restricting the selection of antibiotic-resistant mutants. The strategy is based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth. That concentration has been called the "mutant prevention concentration" (MPC) because no resistant colony is recovered even when >10(10) cells are plated. Resistant mutants are selected exclusively within a concentration range (mutant selection window) that extends from the point where growth inhibition begins, approximated by the minimal inhibitory concentration, up to the MPC. The dimensions of the mutant selection window can be reduced in a variety of ways, including adjustment of antibiotic structure and dosage regimens. The window can be closed to prevent mutant selection through combination therapy with greater than or equal to2 antimicrobial agents if their normalized pharmacokinetic profiles superimpose at concentrations that inhibit growth. Application of these principles could drastically restrict the selection of drug-resistant pathogens.