In vitro analysis of resistance selection by linezolid in vancomycin-susceptible and -resistant Enterococcus faecalis and Enterococcus faecium

被引:19
作者
Allen, George P. [1 ]
Bierman, Betsy C. [1 ]
机构
[1] Oregon Hlth & Sci Univ, Coll Pharm, Oregon State Univ, Portland, OR 97239 USA
关键词
Mutant prevention concentration; Linezolid; Antimicrobial resistance; Enterococci; STAPHYLOCOCCUS-AUREUS; QUINUPRISTIN-DALFOPRISTIN; PHARMACODYNAMIC MODEL; COMBINATION; FLUOROQUINOLONES; INTERMEDIATE; GENTAMICIN; DAPTOMYCIN; STABILITY; INFECTION;
D O I
10.1016/j.ijantimicag.2008.12.011
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The pharmacodynamics of resistance development to linezolid has not been extensively studied, especially when a large bacterial inoculum is exposed to this agent. We simulated the usual therapeutic dose of linezolid, 600 mg intravenously every 12 h [estimated maximum concentration, area under the concentration-time curve (AUC) and half-life of 10.4 mg/L, 61.9 mu g h/mL and 4.8 h, respectively], in an in vitro pharmacodynamic model and investigated the applicability of the mutant selection window (MSW) to linezolid against vancomycin-susceptible and -resistant Enterococcus faecalis and Enterococcus faecium. Four strains were studied, including vancomycin-susceptible (ATCC 29212) and -resistant (ATCC 51299) E. faecalis and vancomycin-susceptible (GP33) and -resistant (GP32) E. faecium. The minimum inhibitory concentration (MIC) for all strains was 2 mg/L; mutant prevention concentration (MPC) values were 4 mg/L for ATCC 29212 and GP33 and 8 mg/L for ATCC 51299 and GP32. Linezolid failed to achieve bactericidal action against ATCC 29212 and GP33 [AUC/MIC = 30.95, AUC/MPC = 15.48, %T(MSW) (% of the dosing interval that concentrations fall in the MSW)= 40%] and ATCC 51299 and GP32 (AUC/MIC = 30.95, AUC/MPC = 7.74, %T(MSW) = 80.1%). Linezolid-resistant subpopulations (MIC = 8 mg/L) of all isolates were selected. Our data suggest that linezolid resistance in enterococci will continue to emerge upon continued use of this antimicrobial. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
引用
收藏
页码:21 / 24
页数:4
相关论文
共 23 条
[1]   In vitro activities of daptomycin, arbekacin, vancomycin, and gentamicin alone and/or in combination against glycopeptide intermediate-resistant Staphylococcus aureus in an infection model [J].
Akins, RL ;
Rybak, MJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (07) :1925-1929
[2]   In vitro activities of quinupristin-dalfopristin and cefepime, alone and in combination with various antimicrobials, against multidrug-resistant staphylococci and enterococci in an in vitro pharmacodynamic model [J].
Allen, GP ;
Cha, R ;
Rybak, MJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (08) :2606-2612
[3]  
[Anonymous], M100S18 CLSI S
[4]   Linezolid resistance in Staphylococcus aureus:: Gene dosage effect, stability, fitness costs, and cross-resistances [J].
Besier, Silke ;
Ludwig, Albrecht ;
Zander, Johannes ;
Brade, Volker ;
Wichelhaus, Thomas A. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (04) :1570-1572
[5]   Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae [J].
Blondeau, JM ;
Zhao, XL ;
Hansen, G ;
Drlica, K .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (02) :433-438
[6]   Pharmacokinetic/pharmaeodynamic factors influencing emergence of resistance to linezolid in an in vitro model [J].
Boak, Lauren M. ;
Li, Jian ;
Rayner, Craig R. ;
Nation, Roger L. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (04) :1287-1292
[7]   Enterococcus faecalis resistant to linezolid:: Case series and review of the literature [J].
Burleson, BS ;
Ritchie, DJ ;
Micek, ST ;
Dunne, WM .
PHARMACOTHERAPY, 2004, 24 (09) :1225-1231
[8]   A comparative in-vitro evaluation of resistance selection after exposure to teicoplanin, vancomycin, linezolid and quinupristin-dalfopristin in Staphylococcus aureus and Enterococcus spp. [J].
Drago, L. ;
Nicola, L. ;
De Vecchi, E. .
CLINICAL MICROBIOLOGY AND INFECTION, 2008, 14 (06) :608-611
[9]   Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid [J].
Gonzales, RD ;
Schreckenberger, PC ;
Graham, MB ;
Kelkar, S ;
DenBesten, K ;
Quinn, JP .
LANCET, 2001, 357 (9263) :1179-1179
[10]   In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis [J].
Kaatz, GW ;
Seo, SM .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (03) :799-801