Greenwood D, O'Grady F
Chemotherapy. 1975;21(6):330-41. doi: 10.1159/000221878.
Several penicillins known to be stable to enterobacterial beta-lactamases were tested in combination with beta-lactamase-sensitive penicillins and cephalosporins in a turbidimetric system. Nafcillin was found to be the best beta-lactamase inhibitor amongst agents presently available commercially, but the related, new semi-synthetic penicillin BRL 1437 (2-isopropoxy-1-naphthylpenicillin) was consistently found to be superior. Using 103 ampicillin-resistant coliform bacilli and antibiotic levels achievable in urine, cephalothin or cephaloridine alone achieved long-term suppression of growth (greater than 20 h) of 16 and 13% of strains, respectively, while the additional presence of BRL 1437 suppressed growth for longer than 20 h of 81% of the remaining strains. Even where 'success' was not achieved according to these stringent criteria, regrowth was significantly delayed by the presence of BRL 1437. Suppression of growth for longer than 20 h by BRL 1437 plus cephalothin was achieved with all of the 46 Escherichia coli strains tested. Antibiotic combinations were also studied in an in vitro model which stimulates the hydrokinetic features of the urinary bladder. Suppression of the growth of two highly resistant E. coli strains was achieved in this system, for therapeutically acceptable periods of time, with combinations of cephalothin or cephaloridine with BRL 1437, but not nafcillin.
在比浊法系统中，对几种已知对肠杆菌β-内酰胺酶稳定的青霉素与对β-内酰胺酶敏感的青霉素及头孢菌素进行了联合测试。发现萘夫西林是目前市售药物中最佳的β-内酰胺酶抑制剂，但一直发现相关的新型半合成青霉素BRL 1437（2-异丙氧基-1-萘基青霉素）更胜一筹。使用103株耐氨苄西林的大肠埃希菌以及尿液中可达到的抗生素水平，单独使用头孢噻吩或头孢利定分别能使16%和13%的菌株实现长期生长抑制（超过20小时），而添加BRL 1437能使其余81%的菌株生长抑制超过20小时。即使按照这些严格标准未取得“成功”，BRL 1437的存在也能显著延迟细菌再生长。在所测试的46株大肠埃希菌中，BRL 1437加头孢噻吩均能实现超过20小时的生长抑制。还在一个模拟膀胱流体动力学特征的体外模型中研究了抗生素联合用药情况。在该系统中，头孢噻吩或头孢利定与BRL 1437联合用药能在治疗可接受的时间段内抑制两种高度耐药的大肠埃希菌菌株生长，但与萘夫西林联合则不能。
