Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Chemotherapy. 2009;55(6):414-7. doi: 10.1159/000263228. Epub 2009 Dec 2.
Antibacterial activity of three members of a benzoxazine series of histidine kinase inhibitors ( 4a , 4b and 6 ) was studied on standard strains, and with 4b also on clinical isolates of enterococci.
Susceptibility to each compound was tested using a broth macrodilution method with a range of dilutions from 0.016 to 128 microg/ml on four standard strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299).
Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 microg/ml, S. aureus ATCC 43300 at 32 microg/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 microg/ml, while 4a and 6 did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5-16 microg/ml.
Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.
研究了苯并恶嗪系列组氨酸激酶抑制剂（4a、4b 和 6）的三个成员对标准菌株和 4b 对临床分离粪肠球菌的抗菌活性。
使用肉汤微量稀释法，在四个标准菌株（大肠杆菌 ATCC 25922、铜绿假单胞菌 ATCC 27853、金黄色葡萄球菌 ATCC 29213 和粪肠球菌 ATCC 29212）和 4b 对 52 株临床分离粪肠球菌（7 株万古霉素敏感粪肠球菌、15 株万古霉素敏感屎肠球菌和 30 株万古霉素耐药屎肠球菌）的 0.016 至 128 μg/ml 范围内的一系列稀释度进行了药敏试验，此外，在两个额外的标准菌株（金黄色葡萄球菌 ATCC 43300 和粪肠球菌 ATCC 51299）上也进行了药敏试验。
两种化合物均不抑制大肠杆菌 ATCC 25922 或铜绿假单胞菌 ATCC 27853 的生长。化合物 4b 在 8 μg/ml 时抑制金黄色葡萄球菌 ATCC 29213、32 μg/ml 时抑制金黄色葡萄球菌 ATCC 43300、16 μg/ml 时抑制粪肠球菌 ATCC 29212 和粪肠球菌 ATCC 51299 的生长，而 4a 和 6 在更高浓度时则抑制生长。对于临床分离的粪肠球菌，4b 的最低抑菌浓度范围为 0.5-16 μg/ml。
化合物 4b 有望成为治疗万古霉素敏感和耐药肠球菌的潜在有用的抗菌药物。
