Midwestern University, Downers Grove, Illinois, USA.
Antimicrob Agents Chemother. 2013 Aug;57(8):3923-7. doi: 10.1128/AAC.00192-13. Epub 2013 Jun 3.
Assessing clinical virulence differences between vancomycin-resistant Enterococcus faecium (VREF) strains resistant to linezolid (LRVRE) and linezolid-susceptible VRE (LSVRE) strains is difficult due to confounding patient variables. Galleria mellonella is a validated host interaction model allowing straightforward organism virulence assessment. The objective of this study was to assess the virulence of VREF in G. mellonella according to linezolid resistance and clinical outbreak status. A genetically related pair of VREF strains with and without genotypically confirmed linezolid resistance was selected for analysis. Additionally, six strains of LSVRE and two strains of LRVRE were selected according to epidemiologic outbreak status. Mortality of G. mellonella was assessed daily over a 5-day period and analyzed using Kaplan-Meier survival curves and log rank tests. Linezolid resistance did not have a significant effect on G. mellonella mortality in the genetically related pair (P = 0.93). There was no significant difference in mortality over time between strains (non-outbreak [i.e., no patient transmissions were recorded] [n = 2] versus outbreak [i.e., transmission occurred between 3 or more patients in a period of 30 days] [n = 6], P = 0.84; extensive transmission [i.e., the isolate was transmitted between at least 80 patients] [n = 2] versus limited transmission [i.e., the isolate was transmitted between fewer than 10 patients] [n = 4], P = 0.78). These results suggest that patients infected with LRVRE or outbreak strains of VREF are at no greater risk of poor outcomes mediated by organism virulence than those infected with LSVRE or non-outbreak strains.
评估耐万古霉素粪肠球菌(VREF)中对利奈唑胺(LRVRE)耐药和利奈唑胺敏感(LSVRE)菌株之间临床毒力差异具有挑战性,因为存在混杂的患者变量。桔小实蝇是一种经过验证的宿主相互作用模型,可直接评估生物体的毒力。本研究的目的是根据利奈唑胺耐药性和临床暴发状态评估 VREF 在桔小实蝇中的毒力。选择一对具有和不具有基因确认的利奈唑胺耐药性的遗传相关 VREF 菌株进行分析。此外,根据流行病学暴发状态选择了 6 株 LSVRE 和 2 株 LRVRE 菌株。在 5 天的时间内每天评估桔小实蝇的死亡率,并使用 Kaplan-Meier 生存曲线和对数秩检验进行分析。在遗传相关的对中,利奈唑胺耐药性对桔小实蝇死亡率没有显著影响(P=0.93)。不同菌株之间死亡率随时间的差异无统计学意义(无暴发[即未记录患者传播] [n=2]与暴发[即 30 天内至少 3 名患者之间发生传播] [n=6],P=0.84;广泛传播[即该分离株在至少 80 名患者之间传播] [n=2]与有限传播[即该分离株在少于 10 名患者之间传播] [n=4],P=0.78)。这些结果表明,与感染 LSVRE 或非暴发株的患者相比,感染 LRVRE 或暴发株的患者在生物体毒力介导的不良结局方面没有更高的风险。