耐药突变选择窗与抗感染药物防突变浓度

防变异浓度 (MPC)是指抗菌药物防止细菌选择第一步耐药突变的最低浓度 ,MPC与MIC(最小抑菌浓度 )的浓度范围为突变选择窗 (MSW )。当血清或组织液药物浓度低于MIC时 ,治疗无效但也不会导致细菌耐药突变体的富集 ;超过MPC时细菌要生长须同时具备两种或以上突变 ,因而不仅治疗成功并且也很难出现耐药突变体的选择性扩增 ;处于窗内时将选择出耐药突变菌 ,即使临床治疗成功率很高。该理论为有效抑制细菌耐药及制定抗菌药物应用策略提供了新的思路和参考依据。

Mutant selection window and mutant prevention concentration for antimicrobial agents

Mutant prevention concentration (MPC) is the lowest concentration threshold that restricts the selection of all single step (next step) mutant subpopulations; and mutant selection window (MSW) is a concentration range extending from MIC to MPC, within which resistant mutants are predominately enriched. When serum drug level is below MIC, no mutant will be enriched because selective pressure is absent, and it will be hardly selected while above MPC mutants because double mutations are required for growth; when within MSW however, mutants are most likely to be selectively enriched even though the clinical treatment may be effective. This theory may provide new approaches for drastically reducing selection of resistance and formulating new strategies for proper antimicrobial use during therapy.