Deshpande Lalitagauri, Rhomberg Paul R, Fritsche Thomas R, Sader Helio S, Jones Ronald N
The JONES Group/JMI Laboratories, North Liberty, IA, USA.
Diagn Microbiol Infect Dis. 2004 Sep;50(1):73-5. doi: 10.1016/j.diagmicrobio.2004.04.011.
BAL9141, the active principle of prodrug BAL5788, is a parenteral cephalosporin active against oxacillin-resistant Staphylococcus aureus. Previous studies have reported the cidal action of BAL9141 towards limited numbers of isolates by time-kill methods. We tested >100 staphylococci, streptococci, and Gram-negative isolates by broth microdilution methods to determine the antibacterial activity of BAL9141 and to compare minimum inhibitory concentrations (MICs) with minimum bactericidal concentrations (MBCs). Among the 53 staphylococcal isolates, all but one (98%) had a, MBC:MIC ratio < or =2. Forty-five percent (five strains) of the penicillin-nonsusceptible Streptococcus pneumoniae isolates had an MBC:MIC ratio >4. Among 22 Enterobacteriaceae, 73% of isolates had MBC:MIC ratios of 2 or less; three strains with ratios greater than 4 were Serratia marcescens. BAL9141 displayed a predominant bactericidal activity against the majority of Gram-positive and -negative species, including resistant subsets, making it an attractive candidate for further development.
前体药物BAL5788的活性成分BAL9141是一种肠道外头孢菌素,对耐苯唑西林金黄色葡萄球菌具有活性。以往研究通过时间杀菌法报道了BAL9141对数量有限的分离株的杀菌作用。我们采用肉汤微量稀释法对100多株葡萄球菌、链球菌和革兰氏阴性菌分离株进行了检测,以确定BAL9141的抗菌活性,并比较最小抑菌浓度(MIC)和最小杀菌浓度(MBC)。在53株葡萄球菌分离株中,除1株外(98%),所有菌株的MBC:MIC比值均≤2。45%(5株)对青霉素不敏感的肺炎链球菌分离株的MBC:MIC比值>4。在22株肠杆菌科细菌中,73%的分离株的MBC:MIC比值为2或更低;3株比值大于4的菌株为粘质沙雷氏菌。BAL9141对大多数革兰氏阳性和阴性菌,包括耐药亚群,均表现出主要的杀菌活性,使其成为进一步开发的有吸引力的候选药物。