Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Int J Antimicrob Agents. 2011 Oct;38(4):301-6. doi: 10.1016/j.ijantimicag.2011.04.023. Epub 2011 Jul 20.
NXL103 (linopristin/flopristin, 30/70) is a novel oral streptogramin combination with activity against a large variety of multidrug-resistant Gram-positive pathogens. The objective of this study was to evaluate the in vitro activity of NXL103 in comparison with oral comparators (clindamycin and linezolid). Six clinical isolates [four meticillin-resistant Staphylococcus aureus (MRSA) and two Streptococcus pyogenes] were exposed for 48 h in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model at a starting inoculum of ca. 10(6) colony-forming units (CFU)/mL. Antimicrobial simulations included NXL103 500 mg every 12 h, linezolid 600 mg every 12 h and clindamycin 450 mg every 6 h. Bactericidal and static effects were defined as ≥3log(10) and <3log(10) CFU/mL kill from the starting inoculum, respectively. Experiments were performed in duplicate to ensure reproducibility, and differences between regimens were evaluated by analysis of variance (ANOVA) with Tukey's post-hoc test. NXL103 exhibited lower minimum inhibitory concentrations than comparators, with values ≤0.06 mg/L for S. pyogenes and 0.125-0.25 mg/L for MRSA isolates. In the PK/PD model, NXL103 demonstrated significantly better activity than linezolid and clindamycin (P<0.05), achieving sustained bactericidal activity within <2 h against S. pyogenes strains and between 7.3-32 h against MRSA isolates. In contrast, linezolid only exhibited a static effect, whereas clindamycin achieved 3log(10) kill at 6h against the unique clindamycin-susceptible S. pyogenes strain evaluated. In conclusion, at therapeutic concentrations NXL103 exhibits promising activity against both MRSA and S. pyogenes strains, including clindamycin-resistant organisms. Further in vitro and in vivo experiments are warranted to explore the therapeutic benefit of NXL103 for the treatment of Gram-positive skin and soft-tissue infections.
NXL103（林可霉素/克林霉素，30/70）是一种新型的口服糖肽类抗生素，对多种耐多药革兰阳性病原体具有活性。本研究旨在评估 NXL103 的体外活性，并与口服对照药物（克林霉素和利奈唑胺）进行比较。在一个起始接种量约为 10（6）菌落形成单位（CFU）/mL 的体外药代动力学/药效学（PK/PD）模型中，对 6 株临床分离株（4 株耐甲氧西林金黄色葡萄球菌[MRSA]和 2 株酿脓链球菌）进行了 48 小时的暴露。抗菌模拟包括 NXL103 500mg 每 12 小时、利奈唑胺 600mg 每 12 小时和克林霉素 450mg 每 6 小时。杀菌和静态效果分别定义为起始接种量减少≥3log（10）和<3log（10）CFU/mL。实验重复进行两次以确保重现性，并通过方差分析（ANOVA）和 Tukey 事后检验评估方案之间的差异。NXL103 的最低抑菌浓度低于对照药物，酿脓链球菌的浓度为≤0.06mg/L，耐甲氧西林金黄色葡萄球菌分离株的浓度为 0.125-0.25mg/L。在 PK/PD 模型中，NXL103 的活性明显优于利奈唑胺和克林霉素（P<0.05），对酿脓链球菌菌株在<2 小时内达到持续杀菌活性，对耐甲氧西林金黄色葡萄球菌分离株在 7.3-32 小时内达到杀菌活性。相比之下，利奈唑胺仅表现出静态作用，而克林霉素对唯一评估的克林霉素敏感的酿脓链球菌菌株在 6 小时时达到 3log（10）的杀菌效果。总之，在治疗浓度下，NXL103 对耐甲氧西林金黄色葡萄球菌和酿脓链球菌菌株均表现出良好的活性，包括对克林霉素耐药的菌株。需要进一步的体外和体内实验来探索 NXL103 治疗革兰阳性皮肤和软组织感染的治疗益处。
