LaPlante Kerry L, Rybak Michael J, Leuthner Kimberly D, Chin Judy N
Anti-Infective Research Laboratory, Pharmacy Practice-4148, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA.
Antimicrob Agents Chemother. 2006 Apr;50(4):1298-303. doi: 10.1128/AAC.50.4.1298-1303.2006.
We inoculated an in vitro pharmacodynamic model simultaneously with clinical isolates of methicillin-resistant Staphylococcus aureus and an enterocin-producing enterococcus (vancomycin-resistant Enterococcus faecalis, ampicillin susceptible) at 7 log10 CFU/ml to examine enterocin effects and antimicrobial activity on staphylococci. The investigated antimicrobial regimens were 100 mg arbekacin every 12 h (q12h), 6 mg daptomycin per kg of body weight/day, 600 mg linezolid q12h, and 100 mg tigecycline q24h alone and in combination (daptomycin, linezolid, and tigecycline) with arbekacin. Simulations were performed in triplicate; bacterial quantification occurred over 48 h, and development of resistance was evaluated throughout. When we evaluated the impact of antimicrobial activity against S. aureus alone, daptomycin demonstrated bactericidal activity (>or=3 log10 CFU/ml kill), whereas arbekacin, linezolid, and tigecycline displayed bacteriostatic activities (<3 log10 CFU/ml kill). In the mixed-pathogen model, early and distinctive stunting of S. aureus growth was noted (1.5 log CFU/ml difference) in the presence of enterocin-producing E. faecalis compared to growth controls run individually (P=0.02). Most noteworthy was that in the presence of enterocin-producing E. faecalis, bactericidal activity was observed with arbekacin and tigecycline and with the addition of arbekacin to linezolid. Antagonism was noted for the combination of tigecycline and arbekacin against S. aureus in the presence of enterocin-producing E. faecalis. Our research demonstrates that the inhibitory effect of E. faecalis contributed significantly to its overall antimicrobial impact on S. aureus. This contribution was enhanced or improved compared to the activity of each antimicrobial alone. Further research is warranted to determine the impact of polymicrobial infections on antimicrobial activity.
我们以7 log10 CFU/ml的浓度，同时将耐甲氧西林金黄色葡萄球菌的临床分离株和一株产肠球菌素的肠球菌（耐万古霉素粪肠球菌，对氨苄西林敏感）接种到体外药效学模型中，以研究肠球菌素对葡萄球菌的作用及抗菌活性。所研究的抗菌方案包括每12小时（q12h）使用100 mg阿贝卡星、每日每千克体重使用6 mg达托霉素、每12小时使用600 mg利奈唑胺、每24小时使用100 mg替加环素，以及这些药物单独使用或与阿贝卡星联合使用（达托霉素、利奈唑胺和替加环素）。模拟实验重复进行三次；在48小时内进行细菌定量，并始终评估耐药性的发展。当我们单独评估抗菌活性对金黄色葡萄球菌的影响时，达托霉素表现出杀菌活性（杀灭≥3 log10 CFU/ml），而阿贝卡星、利奈唑胺和替加环素表现出抑菌活性（杀灭<3 log10 CFU/ml）。在混合病原体模型中，与单独进行的生长对照相比，在存在产肠球菌素的粪肠球菌的情况下，观察到金黄色葡萄球菌生长出现早期且明显的生长迟缓（差异为1.5 log CFU/ml）（P=0.02）。最值得注意的是，在存在产肠球菌素的粪肠球菌的情况下，阿贝卡星和替加环素以及在利奈唑胺中添加阿贝卡星时均观察到杀菌活性。在存在产肠球菌素的粪肠球菌的情况下，观察到替加环素和阿贝卡星联合使用对金黄色葡萄球菌有拮抗作用。我们的研究表明，粪肠球菌的抑制作用对其对金黄色葡萄球菌的总体抗菌影响有显著贡献。与每种抗菌药物单独的活性相比，这种贡献得到了增强或改善。有必要进一步研究以确定多重微生物感染对抗菌活性的影响。
