耐药突变选择窗与抗感染药物防突变浓度

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (1): 1-7.

• 综述与讲座 • 下一篇

耐药突变选择窗与抗感染药物防突变浓度

李燕玉, 裴斐¹ 综述, 赵西林, 王睿审校

空军总医院体检队, 北京100036;
¹解放军总医院临床药理研究室, 北京 100853

收稿日期:2003-06-06 修回日期:2003-08-25 出版日期:2004-01-26 发布日期:2020-11-16
通讯作者: 王睿,女, 研究员, 博士导师, 主要从事临床抗菌药物药理、细菌耐药等研究。Tel:010-66936678 E-mail:wangrui301@95777.com
作者简介:李燕玉, 女, 副主任医师, 博士研究生。Tel:010-66928492 　E-mail:kjliyanyu@263.net；赵西林, 男, 博士, 现工作于美国公共健康研究院, 主要从事抗菌药物药理和细菌耐药研究。

Mutant selection window and mutant prevention concentration for antimicrobial agents

LI Yan-Yu, PEI Fei, ZHAO Xi-Lin, WANG Rui¹

Department of Health Examination, Air Force General Hospital of PLA, Beijing 100036, China;
¹Genearl Hospital of PLA, Beijing 100853, China

Received:2003-06-06 Revised:2003-08-25 Online:2004-01-26 Published:2020-11-16

摘要/Abstract

摘要： 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。

关键词: 防变异浓度, 突变选择窗, 抗菌药物耐药

Abstract: 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.

Key words: mutant prevention concentration, mutant selection window, antibiotic-resistance

中图分类号:

R34
R978.1

李燕玉, 裴斐, 赵西林, 王睿. 耐药突变选择窗与抗感染药物防突变浓度[J]. 中国临床药理学与治疗学, 2004, 9(1): 1-7.

LI Yan-Yu, PEI Fei, ZHAO Xi-Lin, WANG Rui. Mutant selection window and mutant prevention concentration for antimicrobial agents[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(1): 1-7.

参考文献

1 Drlica K.Antibiotic resistance:can we beat the bugs[J] ? Drug Discov Today, 2001;6:714-6
2 Levy SB.Multidrug resistance:a sign of the times[J]. N Engl J Med, 1998;38:1376-8
3 Zhao X.Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolones studies[J]. Clin Infect Dis, 2001;33:S147-56
4 Drlica K.A strategy for fighting antibiotic resistance[J]. ASM News, 2001;67:27-33
5 Drlica K.The future of fluoroquinolones[J]. Ann Med, 2000;32:585-7
6 Dong Y, Zhao X, Domagala J, et al. Effect of fluoroquilonone concentration on selection of resistant mutants of mycobacterium bovis BCG and staphylococcus aureus[J]. Antimicro Agents Chemother, 1999;43:1756-8
7 Dong Y, Zhao X, Kreiswirth BN, et al. Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2000;44:2581-4
8 Zhao X, Drlica K.Restricting the selection of antibiotic-resistant mutant bacteria:measurement and potential use of the mutant selection window[J]. J Infect Dis, 2002;185:561-5
9 Zhao J, Dong Y, Zhao X, et al. Selection of antibiotic-resistant bacterial mutants:allelic diversity among fluoroquilonone-resistant mutantions[J]. J Infect Dis, 2002;182:517-25
10 Nakamura S.Mechanisms of quinolone resistance[J]. J Infect Chemother, 1997;3:128-38
11 Baquero F, Negri MC.Strategies to minimize the development of antibiotic resistance[J]. J Chemother, 1997;9;29-37
12 Blondeau J M, Zhao X, Hansen J, et al. Mutant prevention concentration of fluoroquinolones for clinical isolates of streptococcus pneumoniae[J]. Antimicrob Agents Chemother, 2001;45:433-8
13 Hansen G, Metzler K, Drlica K, et al. Mutant prevention concentration for gemifloxacin with clinical isolates of streptococcus pneumoniae[J]. Antimicro Agents Chemother, 2003;47:440-1
14 Sindelar G, Zhao X, Liew A, et al. Mutant prevention concentration as a measure of fluoroquilonone potency against mycobacteria[J]. Antimicrob Agents Chemother, 2000;44:3337-43
15 Tao L, Zhao X, Li X, et al. Effect of chloramphenicol, erythromycin, moxifloxacin, penicillin and tetracycline concentration on the recovery of resistant mutants of mycobacterium smegmatis and staphylococcus aureus[J]. In press
16 Zhao X, Eisner W, Perl-Rosenthal N, et al. Mutant prevention concentration of garenoxacin (BMS-284756) for ciprofloxa- cin-susceptible or-resistant staphylococcus aureus[J]. Antimicrob Agents Chemother, 2003;47:1023-7
17 Li XY, Zhao XL, Drlica K.Selection of streptococcus pneumonia mutants having reduced susceptibility to moxifloxacin and levofloxacin[J]. Antimicro Agents Chemother, 2002;46:522-4
18 Tillotson G, Zhao X and Drlica K.Fluoroquilonenes as pneumococcal therpy:closing the barn door before the horse escapes[J]. Lancet Inf Dis, 2001;1:145-6
19 Drlica K, Malik M.Fluoroquilonones:action and resistance[J]. Curr Top Med Chem, 2003;3:249-82
20 Zhao XL, Chen X, Domagala J, et al. DNA topoisomerase targets of the fluoroquilonens:a strategy for avoiding bacterial resistance[J]. Proc Natl Sci USA, 1997;94:13991-6
21 Dong YZ, Chen X, Zhao XL, et al. Fluoroquinolone action against mycobacteria:effects of C-8 substituents on growth, survival and resistance[J]. Antimicro Agents Chemother, 1998;42:2978-84
22 Xu C, Kreiswirth BN, Sreevastan S, et al. Fluoroquinolones resistance associated with specific gray se mutations in clinical isolates in multidrug resistant my cobacterium tuberculosis[J]. J Infect Dis, 1996;174:1127-30
23 Vernon A, Burman W, Benator D, et al. Acquinred rifamy cin monoresistance in paients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid[J]. Lancet, 1999;353:1843-7
24 Firsov AA, Vostrov SN, Lubenko IY, et al. In vitro pharmacodynamics evaluation of the mutant selection window hypothesis using four fluoroquinolones against staphylococcus aureus[J]. Antimicrob Agents Chemother, 2003;47:1604-13
25 Pestova E, Beyer R, Cianciotto NP, et al. Contribution of topoisomerase Ⅳ and DNA grayse mutations in streptococcus pneumoniae to resistance to novel fluoroquilonones[J]. Antimicro Agents Chemother, 1999;43:2000-4
26 Sieradzki K, Roberts R, Haber S, et al. The development of the vancomy cin resistance in a patient with methicillin-resistant Staphylococuus aureus infection[J]. N Engl JMed, 1999;340:517-23
27 Craig WA.Pharmocokinetic pharmocosynamic parameters:rational for antibacterial dosing of mice and men[J]. Clin Infect Dis, 1998;26:1-12
28 Gould IM, MacKenzie FM, et al. Antibiotic exposure as a risk factor for emergence of resistance:the influence of concentration[J]. J ApplMicrob Sympo Suppl, 2002;92:78s-84s

[1]	徐丽丽，陈春林，刘桢宇，胡文. 夫西地酸联合头孢类抗生素缩小金黄色葡萄球菌耐药突变选择窗的研究[J]. 中国临床药理学与治疗学, 2016, 21(9): 995-1000.
[2]	黄瀚, 刘世坤. 对抗菌药物防突变浓度及突变选择窗两概念的探讨与思索[J]. 中国临床药理学与治疗学, 2008, 13(1): 21-24.
[3]	崔俊昌, 刘又宁, 王睿, 童卫杭, 梁蓓蓓. 左氧氟沙星药代动力学/药效动力学参数与金黄色葡萄球菌耐药的相关性研究[J]. 中国临床药理学与治疗学, 2007, 12(9): 989-992.
[4]	李朝霞, 刘又宁, 王睿, 童卫杭, 程仕虎. 左氧氟沙星联合万古霉素缩小金黄色葡萄球菌耐药突变选择窗的初步研究[J]. 中国临床药理学与治疗学, 2007, 12(8): 911-914.
[5]	李朝霞, 刘又宁, 王睿, 崔俊昌, 程仕虎, 童卫杭. 氟喹诺酮类药物对金黄色葡萄球菌及其耐药突变体的耐药性研究[J]. 中国临床药理学与治疗学, 2006, 11(6): 696-701.

耐药突变选择窗与抗感染药物防突变浓度

Mutant selection window and mutant prevention concentration for antimicrobial agents

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价