Anderegg Tamara R, Jones Ronald N
The JONES Group/JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
Int J Antimicrob Agents. 2004 Jan;23(1):6-10. doi: 10.1016/j.ijantimicag.2003.05.007.
Rapid expansion of antimicrobial resistance has led to the development of new antimicrobial agents. AZD2563 is a novel oxazolidinone that has activity similar to linezolid and the potential for extended dosing intervals. Recent Gram-positive clinical organisms (1572 strains) were tested including four oxazolidinone-resistant enterococci. Strains processed were: 313 Staphylococcus aureus, 299 coagulase-negative staphylococci, 305 enterococci, 305 Streptococcus pneumoniae, 300 other streptococci (beta-haemolytic and viridans group) and 50 other rarely isolated Gram-positive species. The methods (agar and broth dilution, disk diffusion) of the National Committee for Clinical Laboratory Standards (NCCLS; M7-A6, M2-A8) were followed and linezolid was used as a control agent. A tentative MIC breakpoint (<or=2mg/l) for AZD2563 was based on the manufacturer's recommendation, preliminary pharmacodynamic information and similarity to the current linezolid interpretive criteria. Correlation between AZD2563 MIC values and zone diameters around 30 microg AZD2563 disks indicated a 99.9% categorical agreement and all intermethod errors were minor. Comparison of agar dilution to broth microdilution MIC results for AZD2563 showed 100.0% agreement +/- one log(2) dilution step (89.2% of MIC results were identical). Scattergrams suggest that all Gram-positive organisms could be accurately tested using the same interpretive criteria: susceptible at <or=2mg/l (>or=20 mm), intermediate at 4 mg/l (17-19 mm) and resistant at >or=8 mg/l (<or=16 mm). These tentative AZD2563 interpretive guidelines should facilitate in vitro susceptibility testing during clinical trials and detect all oxazolidinone-resistant isolates.
抗菌药物耐药性的迅速扩展促使了新型抗菌药物的研发。AZD2563是一种新型恶唑烷酮类药物，其活性与利奈唑胺相似，且具有延长给药间隔的潜力。对近期的革兰氏阳性临床菌株（1572株）进行了检测，包括4株对恶唑烷酮耐药的肠球菌。所检测的菌株包括：313株金黄色葡萄球菌、299株凝固酶阴性葡萄球菌、305株肠球菌、305株肺炎链球菌、300株其他链球菌（β溶血性和草绿色链球菌群）以及50株其他罕见的革兰氏阳性菌。采用了美国国家临床实验室标准委员会（NCCLS；M7-A6、M2-A8）的方法（琼脂和肉汤稀释法、纸片扩散法），并以利奈唑胺作为对照药物。基于制造商的建议、初步的药效学信息以及与当前利奈唑胺解释标准的相似性，确定了AZD2563的暂定最低抑菌浓度（MIC）断点（≤2mg/l）。AZD2563的MIC值与含30μg AZD2563纸片周围抑菌圈直径之间的相关性显示，分类一致性为99.9%，所有方法间误差均较小。AZD2563琼脂稀释法与肉汤微量稀释法MIC结果的比较显示，一致性为100.0%±一个对数（2）稀释步长（89.2%的MIC结果相同）。散点图表明，使用相同的解释标准可以准确检测所有革兰氏阳性菌：MIC≤2mg/l（抑菌圈直径≥20mm）为敏感，4mg/l（抑菌圈直径17 - 19mm）为中介，MIC≥8mg/l（抑菌圈直径≤16mm）为耐药。这些暂定的AZD2563解释指南应有助于临床试验期间的体外药敏试验，并检测出所有对恶唑烷酮耐药的分离株。
