Johnson D M, Jones R N, Erwin M E
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Diagn Microbiol Infect Dis. 1999 Feb;33(2):87-91. doi: 10.1016/s0732-8893(98)00104-7.
SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.
SB - 265805（原LB20304）是一种新型的C - 7吡咯烷取代萘啶酮，具有广谱活性，尤其对革兰氏阳性球菌活性显著。将SB - 265805的活性与环丙沙星、格帕沙星、莫西沙星、司帕沙星及青霉素针对从北美和南美30多个医疗中心近期分离出的599株链球菌属菌株进行了比较。其中包括70株对近期上市的氟喹诺酮类药物（左氧氟沙星MIC，≥4微克/毫升）敏感性降低的菌株。所有菌株均采用参考微量稀释法在添加了溶解马血的Mueller - Hinton肉汤中进行检测。148株β溶血性链球菌（B组和C组菌株）中有16%对青霉素不敏感，而草绿色链球菌和肺炎链球菌分别有38%和42%对青霉素耐药。SB - 265805对301株肺炎球菌的效力（MIC90为0.06微克/毫升）比莫西沙星高4倍，比其他喹诺酮类药物效力高≥8倍。针对β溶血性链球菌，SB - 265805和莫西沙星活性最强（MIC90分别为0.06和0.25微克/毫升），而司帕沙星、格帕沙星和环丙沙星（MIC90为0.5 - 1微克/毫升）效力较低。SB - 265805对草绿色链球菌的MIC（MIC90为0.12微克/毫升）比司帕沙星或格帕沙星低4倍，比莫西沙星活性高2倍。一项符合NCCLS M23 - T3指南的九实验室质量控制（QC）方案显示，SB - 265805对肺炎链球菌ATCC 49619的MIC模式值为0.016微克/毫升（建议的QC范围为0.008至0.03微克/毫升）。SB - 265805纸片（5微克）的QC范围为28 - 34毫米（97.3%的合格结果）。总体而言，SB - 265805对链球菌属的体外活性优于司帕沙星、格帕沙星和莫西沙星，明显大于环丙沙星。这种抗菌效力程度值得对这种新药针对链球菌感染的潜在人体临床应用进行进一步研究。
