基于防突变浓度的新型药动学-药效学-突变选择窗同步模型在临床用药上的指导作用

摘要/Abstract

摘要： 文章综述了抗菌药药动学/药效学(PK/PD)模型的发展,详细阐述新型药动物学/药效学模型在抑制细菌耐药突变上的作用,为合理用药及新药研发提供指导,并指出了临床应用所存在的问题。

Abstract: Development history of pharmacokinetic/pharmacodynamic(PK/PD) model for antimicrobial drugs was reviewed in the present article, including the important role of new PK/PD model in inhibition bacterial resistance mutation, intruction in the rational design of drug regimen and new drug investigation. In addition, problems of clinical application of PK/PD model were also discussed.

Key words: PK/PD model; mutant selection window; resistance; rational drug administration

中图分类号:

S859

廖雪玲, 张炳旭, 丁焕中. 基于防突变浓度的新型药动学-药效学-突变选择窗同步模型在临床用药上的指导作用[J]. , 2013, 40(1): 199-203.

LIAO Xue-ling, ZHANG Bing-xu, DING Huan-zhong. Instruction Function in Drug Administration on the New PK-PD-MSW Modeling Based on Mutant Prevent Concentration[J]. China Animal Husbandry & Veterinary Medicine, 2013, 40(1): 199-203.

参考文献

1 刘明涛,盛美艳,张芸,等. 环丙沙星联合妥布霉素对兔铜绿假单胞菌环丙沙星耐药突变选择窗的影响[J]. 中华医学杂志,2011, 91(20): 1427~1431.
2 刘洋,徐刚,王敏,等. 酒石酸泰乐菌素联合阿莫西林钠缩小猪链球菌耐药突变选择窗的研究[J]. 中国预防兽医学报,2010, 32(1): 65~67.
3 孙恩华,刘明涛,毕少杰,等. 美罗培南及头孢他啶与其他抗菌药物联合应用对铜绿假单胞菌耐药突变选择窗的研究[J]. 中华医院感染学杂志,2011, 21(4): 631~633.
4 Almeida D, Nuermberger E, Tyagi S, et al. In vivo validation of the mutant selection window hypothesis with moxifloxacin in a murine model of tuberculosis[J]. Antimicrobial Agents and Chemotherapy, 2007, 51(12):4261~4266.
5 Baquero F, Neqri M C. Strategies to minimize the development of antibiotic resistance[J]. Journal of Chemotherapy, 1997, 9(5): 29~37.
6 Blonedau J M, Hansen G, Metzler K, et al. The role of PK/PD parameters to avoid selection and increase of resistance: Mutant prevention concentration[J]. Journal of Chemotherapy, 2004, 16(3): 1~19.
7 Craig W A. Pharmaconamics of antimicrobials: General concepts and applications. In: Nightingale C, Murakawa T, Ambrose P, eds. Antimicrobial pharmacodynamics in theory and clinical practice, New York: Murcel Dekker, 2002.
8 Credito K, Kosowska-Shick K, McGhee P, et al. Comparative study of the mutant prevention concentrations of moxifloxacin, levofloxacin, and gemifloxacin against Pneumococci[J]. Antimicrobial Agents and Chemotherapy, 2009, 54(2):673~677.
9 Croisier D, Etienne M, Piroth L, et al. In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: Impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants[J]. Journal of Antimicrobial Chemotherapy, 2004, 54(3):640~647.
10 Cui J C, Liu Y N, Wang R, et al. The mutant selection window in rabbits infected with Staphylococcus aureus[J]. The Journal of Infectious Diseases, 2006, 194(11): 1601~1608.
11 Drlica K, Zhao X. Mutant selection window hypothesis updated[J]. Clinical Infectious Disease, 2007, 44(5):681~688.
12 Drlica K. The mutant selection window and antimicrobial resistance[J]. Journal of Antimicrobial Chemotherapy, 2003, 52(1):11~17.
13 Ferran A A, Kesteman A S, Toutain P L, et al. Pharmacokinetic/pharmacodynamic analysis of the influence of inoculum size on the selection of resistance in Escherichia coli by a Quinolone in a mouse thigh bacterial infection model[J]. Antimicrobial Agents and Chemotherapy, 2009, 53(8): 3384~3390.
14 Firsov A A, Vostrov S N, Lubenko I Y, et al. In vitro pharmacodynamic evaluation of the mutant selection window hypothesis using four fluoroquinolones against Staphylococcus aureus[J]. Antimicrobial Agents and Chemotherapy, 2003, 47(5):1604~1613.
15 Gloede J, Scheerans C, Derendorf H, et al. In vitro pharmacodynamic models to determine the effect of antibacterial drugs[J]. Journal of Antimicrobial Chemotherapy, 2009, 65(2):186~201.
16 Jacobs M R, Felmingham D, Appelbaum P C, et al. The alexander project 1998~2000: Susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents[J]. Journal of Antimicrobial Chemotherapy, 2003, 52(2):229~246.
17 Jumbe N, Louie A, Deziel M R, et al. Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy[J]. Journal of Clinical Investigation, 2003, 112(2):275~285.
18 Liang B B, Bai N, Cai Y, et al. Mutant prevention concentration-based pharmacokinetic/pharmacodynamic indices as dosing targets for suppressing the enrichment of levofloxacin-resistant subpopulations of Staphylococcus aureus[J]. Antimicrobial Agents and Chemotherapy, 2011, 55(5):2409~2412.
19 Liu Y, Cui J C, Wang R, et al. Selection of rifampicin-resistant Staphylococcus aureus during tuberculosis therapy: Concurrent bacterial eradication and acquisition of resistance[J]. Journal of Antimicrobial Chemotherapy, 2005, 56(6):1172~1175.
20 Mallk M, Hoatam G, Chavda K, et al. Novel approach for comparing the abilities of quinolones to restrict the emergence of resistant mutants during quinolone exposure[J]. Antimicrobial Agents and Chemotherapy, 2009, 54(1):149~156.
21 Nielsen E I, Cars O, Friberg L E. Pharmacokinetic/Pharmacodynamic (PK/PD) indices of antibiotics predicted by a semimechanistic PKPD model: A step toward model-based dose optimization[J]. Antimicrobial Agents and Chemotherapy, 2011, 55(10):4619~4630.
22 Pope C F, O’Sullivan D M, Mchugh T D, et al. A practical guide to measuring mutation rates in antibiotic resistance[J]. Antimicrobial Agents and Chemotherapy, 2008, 52(4):1209~1214.
23 Sindelar G, Zhao X, Liew A, et al. Mutant prevention concentration as a measure of fluoroquinolone potency against Mycobacteria[J]. Antimicrobial Agents and Chemotherapy, 2000, 44(12):3337~3343.
24 Yuan Z, Ledesma K R, Singh R, et al. Quantitative assessment of combination antimicrobial therapy against multidrug-resistant bacteria in a murine pneumonia model[J]. The Journal of Infectious Diseases, 2010, 201(6):889~897.
25 Zhou J F, Dong Y Z, Zhao X L, et al. Selection of antibiotic-resistant bacterial mutants: Allelic diversity among fluoroquinoloue-resistant mutations[J]. The Journal of Infectious Diseases, 2000, 182(8): 517~525.
26 Zinner S H, Lubenko I U, Gilbert D, et al. Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin concentrations inside and outside the mutant selection window: Related changes in susceptibility, resistance frequency and bacterial killing[J]. Journal of Antimicrobial Chemotherapy, 2003, 52(4):616~622.

[1]	于堃, 赵杰, 马芹, 石艳红, 张筱, 刘子涵, 张新婷, 汪建华, 李玉峰. 商品肉鸭致病性肠炎沙门菌的分离鉴定及耐药性与致病性分析[J]. 中国畜牧兽医, 2025, 52(5): 2353-2363.
[2]	龙宝琴, 王辉翔, 余林金, 哈尔勒哈·阿曼太, 陈浩然, 许梦娇, 史陇兴, 李有文. 2株鹌鹑源肺炎克雷伯菌的分离鉴定及生物学特性分析[J]. 中国畜牧兽医, 2025, 52(5): 2364-2378.
[3]	武佳鑫, 孙月, 毛伟, 刘淑英, 尹凯雯, 张志丹, 韩凯凡, 赵红霞. 羊呼吸道溶血性曼氏杆菌的分离鉴定及其致病性和耐药性研究[J]. 中国畜牧兽医, 2025, 52(5): 2421-2431.
[4]	蔺冰冰, 赵洪哲, 关娜, 乌日古木拉, 其根, 张杨, 温永俊, 王凤雪. 内蒙古部分地区牛源产气荚膜梭菌的分离鉴定及耐药性分析[J]. 中国畜牧兽医, 2025, 52(4): 1873-1883.
[5]	尹凯雯, 毛伟, 曹金山, 孙月, 董海燕, 韩凯凡, 王博, 李培锋, 张志丹, 樊宏亮, 郭宇, 赵红霞. 内蒙古地区牛呼吸道感染的主要病原菌及支原体分离鉴定及耐药性和毒力基因检测[J]. 中国畜牧兽医, 2025, 52(3): 1328-1341.
[6]	李娜, 刘重阳, 张靖靖, 玛丽雅其其格, 珠娜, 陆斌, 海鹰. 1株羊源D型产气荚膜梭菌的分离鉴定及耐药性分析[J]. 中国畜牧兽医, 2025, 52(3): 1352-1359.
[7]	李扬, 徐晶晶, 张小玉, 李娜娜, 余星雨, 冷青文, 李彦芳, 屈勇刚. 新疆某规模化奶牛场乳源金黄色葡萄球菌的分离鉴定、耐药分析及毒力基因检测[J]. 中国畜牧兽医, 2025, 52(3): 1370-1382.
[8]	戴婷婷, 陈海玉, 段楚楚, 刘荣昌, 李宇蓉, 严淑涵, 陈梦诗, 刘露薇, 包银莉, 程艳青, 林炜明, 黄翠琴, 郑新添. 鸡源携带多黏菌素耐药基因mcr-1大肠杆菌耐药性与毒力基因相关性分析[J]. 中国畜牧兽医, 2025, 52(3): 1393-1404.
[9]	刘泽武, 樊月圆, 袁嘉芮, 格桑卓嘎, 班旦, 白卫兵, 茶金龙, 四朗玉珍, 富国文. 1株羊源伪结核棒状杆菌的分离鉴定及耐药性分析[J]. 中国畜牧兽医, 2025, 52(3): 1405-1415.
[10]	李娜娜, 余星雨, 侯宫明珠, 李扬, 郭亚奇, 郑培, 李彦芳, 梁晏, 何高明, 屈勇刚. 猪源霍氏肠杆菌的分离鉴定及其耐药性、致病性分析[J]. 中国畜牧兽医, 2025, 52(1): 376-388.
[11]	廖慧群, 赵美, 曾国辉, 苏仁伟, 邓衔柏. 林麝源肺炎克雷伯菌耐药性及毒力基因分析[J]. 中国畜牧兽医, 2025, 52(1): 411-421.
[12]	马振, 王隆胜, 唐泽宇, 闵鹏飞, 赵健豪, 孟凡奇, 薛书江, 贾立军. 珲春敬信湿地候鸟白额雁恶臭假单胞菌的分离鉴定及药物敏感性分析[J]. 中国畜牧兽医, 2025, 52(1): 461-469.
[13]	赵星, 梁军, 李阳, 杨丹娇, 陈朝喜. 河曲马源大肠杆菌耐药相关基因检测及外排泵抑制剂对其生物被膜的影响[J]. 中国畜牧兽医, 2024, 51(8): 3603-3614.
[14]	焦凤超, 雷震, 李迎晓, 武娴, 曲哲会. 一株孔雀源奇异变形杆菌全基因组测序及毒力与耐药性分析[J]. 中国畜牧兽医, 2024, 51(7): 3030-3040.
[15]	陈亦杏, 张美琳, 李仕楷, 杨智灿, 李宛珈, 陈济铛, 朱婉君, 张济培. 广东部分地区鸭疫里默氏杆菌的分离鉴定和耐药性分析[J]. 中国畜牧兽医, 2024, 51(7): 3185-3194.