Motohiro T, Tanaka K, Koga T, Shimada Y, Tomita N, Nishiyama T, Ishimoto K, Tominaga K, Iriki T, Harada M
Jpn J Antibiot. 1985 Feb;38(2):481-506.
MICs of BRL 25000, a combination of a newly developed beta-lactamase inhibitor CVA and AMPC in the ratio of 1 to 2, were determined against a number of bacterial strains and compared with those of AMPC, CVA, CEX and CCL. The 98 bacterial strains tested included 2-S. aureus, 23-H. influenzae, 25-E. coli, 22-K. pneumoniae and 26-P. mirabilis. In pharmacokinetic studies, BRL 25000 medium granules were administered to groups of 3 male subjects, aged between 7 years 8 months and 9 years 5 months, at doses of 10, 15 and 20 mg/kg, 2 hours after a meal. The resultant serum and urine concentrations and drug recoveries were measured. Furthermore, BRL 25000 was administered to a total 43 patients (2-pharyngitis, 8-tonsillitis, 3-bronchitis, 2-pneumonia and 28-urinary tract infection) whom clinically evaluable. An average daily dosage of 45.3 mg/kg was given, in 3 or 4 divided doses, for a period of 8 days on average. Clinical and bacteriological effects as well as side effects were studied. In the microbiological studies on 98 clinical strains, including beta-lactamase negative bacteria, BRL 25000 showed MICs against the Gram-positive cocci (2-S. aureus) superior to the other 4 drugs at inoculum sizes of 10(8) and 10(6) cells/ml. For the Gram-negative bacilli, against H. influenzae at inoculum sizes of 10(8) and 10(6) cells/ml, BRL 25000 was inferior in the small MIC range but superior in the large MIC range to AMPC, and was superior to the other 3 drugs. Against E. coli at an inoculum of 10(8) cells/ml, BRL 25000 showed antibacterial activity next to AMPC and CCL whilst at an inoculum of 10(6) cells/ml, it was inferior in the small MIC range but superior in the large MIC range to AMPC and CEX and was inferior to CCL but superior to CVA. Against K. pneumoniae at an inoculum of 10(8) cells/ml, BRL 25000 was equal to AMPC, CVA and CEX but inferior to CCL, whilst at an inoculum of 10(6) cells/ml, it was inferior to CCL but superior to the other 3 drugs. Against P. mirabilis at inoculum sizes of 10(8) and 10(6) cells/ml, BRL 25000 was inferior in the small MIC range but equal or superior in the large MIC range to AMPC, and was superior to CVA and CEX.(ABSTRACT TRUNCATED AT 400 WORDS)
测定了新型β-内酰胺酶抑制剂CVA与阿莫西林（AMPC）以1:2比例组合的BRL 25000对多种细菌菌株的最低抑菌浓度（MIC），并与AMPC、CVA、头孢克肟（CEX）和氯碳头孢（CCL）的MIC进行比较。所检测的98株细菌包括2株金黄色葡萄球菌、23株流感嗜血杆菌、25株大肠杆菌、22株肺炎克雷伯菌和26株奇异变形杆菌。在药代动力学研究中，将BRL 25000的中等颗粒剂在餐后2小时以10、15和20mg/kg的剂量给予3组年龄在7岁8个月至9岁5个月之间的男性受试者。测定了血清和尿液中的药物浓度以及药物回收率。此外，对43例临床可评估的患者（2例咽炎、8例扁桃体炎、3例支气管炎、2例肺炎和28例尿路感染）给予BRL 25000。平均每日剂量为45.3mg/kg，分3或4次给药，平均给药8天。研究了临床和细菌学效果以及副作用。在对包括β-内酰胺酶阴性细菌在内的98株临床菌株的微生物学研究中，在接种量为10⁸和10⁶个细胞/ml时，BRL 25000对革兰氏阳性球菌（2株金黄色葡萄球菌）的MIC优于其他4种药物。对于革兰氏阴性杆菌，在接种量为10⁸和10⁶个细胞/ml时，BRL 25000在小MIC范围内低于AMPC，但在大MIC范围内优于AMPC，且优于其他3种药物。在接种量为1×10⁸个细胞/ml时，BRL 25000对大肠杆菌的抗菌活性仅次于AMPC和CCL，而在接种量为10⁶个细胞/ml时，它在小MIC范围内低于AMPC和CEX，但在大MIC范围内优于它们，且低于CCL但优于CVA。在接种量为10⁸个细胞/ml时，BRL 25000对肺炎克雷伯菌的效果与AMPC、CVA和CEX相当，但低于CCL，而在接种量为10⁶个细胞/ml时，它低于CCL但优于其他3种药物。在接种量为10⁸和10⁶个细胞/ml时，BRL 25000在小MIC范围内低于AMPC，但在大MIC范围内与AMPC相当或优于AMPC，且优于CVA和CEX。（摘要截断于400字）
