Dailey C F, Dileto-Fang C L, Buchanan L V, Oramas-Shirey M P, Batts D H, Ford C W, Gibson J K
Pharmacology, Pharmacia, Kalamazoo, Michigan 49001, USA.
Antimicrob Agents Chemother. 2001 Aug;45(8):2304-8. doi: 10.1128/AAC.45.8.2304-2308.2001.
The efficacies of orally (p.o.) dosed linezolid and intravenously (i.v.) dosed vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits with experimental aortic-valve endocarditis were investigated. After endocarditis was established with a recent clinical MRSA isolate, rabbits were dosed for 5 days with linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of body weight or vancomycin (i.v., twice a day) at 25 mg/kg. The 25-mg/kg linezolid group had a high mortality rate and bacterial counts in the valve vegetations that were not different from those of the controls. Linezolid dosed p.o. at 50 and 75 mg/kg and i.v. vancomycin produced statistically significant reductions in bacterial counts compared to those of the untreated controls. The reduced bacterial counts and culture-negative valve rates for the animals treated with linezolid at 75 mg/kg were similar to those for the vancomycin-treated animals. Concentrations of linezolid in plasma were determined at several points in the dosing regimen. These results suggest that the efficacy of linezolid in this infection model is related to trough levels in plasma that remain above the MIC for this microorganism. At the ineffective dose of linezolid (25 mg/kg) the concentration at sacrifice was 0.045 times the MIC, whereas the concentrations of linezolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC at sacrifice, respectively. The results from this experimental model suggest that the oxazolidinone linezolid may be effective for the treatment of serious staphylococcal infections when resistance to other antimicrobials is present.
研究了口服利奈唑胺和静脉注射万古霉素对患有实验性主动脉瓣心内膜炎的兔体内耐甲氧西林金黄色葡萄球菌（MRSA）的疗效。用近期临床分离的MRSA菌株建立心内膜炎模型后，兔分别接受为期5天的利奈唑胺（口服，每日3次）治疗，剂量为25、50或75mg/kg体重，或万古霉素（静脉注射，每日2次）治疗，剂量为25mg/kg。25mg/kg利奈唑胺组死亡率高，瓣膜赘生物中的细菌计数与对照组无差异。口服50和75mg/kg利奈唑胺以及静脉注射万古霉素与未治疗的对照组相比，细菌计数有统计学意义的显著降低。75mg/kg利奈唑胺治疗的动物的细菌计数降低和瓣膜培养阴性率与万古霉素治疗的动物相似。在给药方案的几个时间点测定了血浆中利奈唑胺的浓度。这些结果表明，利奈唑胺在该感染模型中的疗效与血浆谷浓度有关，该浓度保持高于该微生物的最低抑菌浓度（MIC）。在无效剂量的利奈唑胺（25mg/kg）下，处死时的浓度为MIC的0.045倍，而50和75mg/kg组处死时血浆中利奈唑胺的浓度分别为MIC的2倍和5倍。该实验模型的结果表明，当对其他抗菌药物耐药时，恶唑烷酮类药物利奈唑胺可能对治疗严重葡萄球菌感染有效。
