Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus
Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus
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DOI：
10.1111/j.1469-0691.2010.02956.x
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发表时间：
2010-07-01
影响因子：
14.2
通讯作者：
Stobberingh, E. E.
中科院分区：
文献类型：
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作者：
Croes, S.;Beisser, P. S.;Stobberingh, E. E.
由于目前尚不清楚β -内酰胺类抗菌剂是否能有效地对抗临界耐奥西林金黄色葡萄球菌（BORSA），当奥西林mic >= 4 mg/L时，我们评估了奥西林对临床BORSA分离株的体外杀菌活性和药效学效果。并与万古霉素、达托霉素和利奈唑胺对氧苄西林mic值>= 4 mg/L和氧苄西林mic值< 2 mg/L的BORSA的作用效果进行了比较。此外，考虑到β -内酰胺酶产生和质粒谱分析的影响，以澄清对oxacillin的反应。与ATCC 29213相比，Oxacillin对BORSA的杀伤活性减弱，因为药效学参数显示，当Oxacillin mic >= 4 mg/L时，Oxacillin对BORSA的效价明显降低（约10倍）。含有氧苄西林mic < 2 mg/L的BORSA的pbora53样质粒再生能力明显增强。综上所述，oxacillin在根除(i) oxacillin mich0 = 4 mg/L的BORSA或(ii) β -内酰胺酶分泌过量的BORSA （mich0 < 2 mg/L）方面无效。为了避免可能的治疗失败，有必要进一步研究针对不同BORSA菌株的β -内酰胺剂量策略。
P>Since it is unknown whether beta-lactam antimicrobial agents can be used effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) with oxacillin MICs >= 4 mg/L, the in vitro bactericidal activity and pharmacodynamic effect of oxacillin against clinical BORSA isolates was evaluated. Time-kill experiments with oxacillin were performed and the results compared with those obtained with vancomycin, daptomycin and linezolid against BORSA with oxacillin MICs >= 4 mg/L and BORSA with oxacillin MICs < 2 mg/L. Furthermore, the effect of beta-lactamase production and plasmid profile analysis were taken into account to clarify responses to oxacillin. Oxacillin killing activity was attenuated against BORSA compared with ATCC 29213 since the pharmacodynamic parameters revealed that the potency of oxacillin was markedly reduced (c. ten-fold) against BORSA with oxacillin MICs >= 4 mg/L. pBORa53-like plasmid-containing BORSA with oxacillin MICs < 2 mg/L showed markedly more regrowth. In conclusion, oxacillin was non-effective in the eradication of either (i) BORSA with oxacillin MICs >= 4 mg/L or (ii) beta-lactamase-hyperproducing BORSA (MICs < 2 mg/L). Further investigation into beta-lactam dosing strategies against different BORSA strains is warranted in order to avoid possible therapy failure.