Downs J T, Andriole V T
Yale J Biol Med. 1980 Mar-Apr;53(2):149-59.
The in vitro activity of a unique new 1-oxa cephalosporin beta-lactam antibiotic (LY 127935) was tested against clinical isolates of gram-positive and gram-negative bacteria and compared with the activities of cefoxitin, cefamandole, cephalothin, clindamycin, amikacin, tobramycin, gentamicin, ticarcillin, and carbenicillin. The new compound was observed to have a broad spectrum of antibacterial activity which far exceeded the activity of older cephalosporins against aerobic gram-negative enteric bacilli. This new compound was the most active drug tested against Klebsiella, Serratia, Enterobacter, indole-negative and positive Proteus species, and E. coli. Against clinical isolates of Pseudomonas species the new compound was more active than cefoxitin, cefamandole, cephalothin, and clindamycin, comparable to ticarcillin and carbenicillin, and less active than gentamicin, tobramycin, and amikacin. Yet, most of the Pseudomonas isolates were inhibited by 16 micrograms/ml of the new compound. Against both beta-lactamase and non beta-lactamase producing Staphylococcus aureus isolates, the new 1-oxa compound was less active than the older cephalosporins of which cephalothin and cefamandole were the most effective. The 1-oxa compound had no appreciable activity against isolates of Streptococcus faecalis. Activity of all four cephalosporins studied was decreased in the presence of an increased inoculum of Enterobacteriaceae in trypticase soy and Mueller-Hinton broth. The activity of the new compound against Pseudomonas species was also decreased by an increased inoculum in Mueller-Hinton but not in trypticase soy broth. These results indicate that this new 1-oxa compound may have great promise as a broad spectrum antibiotic and may warrant controlled clinical trials in man.
对一种独特的新型1-氧杂头孢菌素β-内酰胺抗生素（LY 127935）的体外活性进行了测试，以检测其对革兰氏阳性菌和革兰氏阴性菌临床分离株的作用，并与头孢西丁、头孢孟多、头孢噻吩、克林霉素、阿米卡星、妥布霉素、庆大霉素、替卡西林和羧苄西林的活性进行比较。观察到这种新化合物具有广谱抗菌活性，其对需氧革兰氏阴性肠道杆菌的活性远远超过了老一代头孢菌素。这种新化合物是测试药物中对克雷伯菌属、沙雷菌属、肠杆菌属、吲哚阴性和阳性变形杆菌属以及大肠杆菌最具活性的药物。对于铜绿假单胞菌临床分离株，新化合物比头孢西丁、头孢孟多、头孢噻吩和克林霉素更具活性，与替卡西林和羧苄西林相当，比庆大霉素、妥布霉素和阿米卡星活性低。然而，大多数铜绿假单胞菌分离株在16微克/毫升的新化合物作用下受到抑制。对于产生β-内酰胺酶和不产生β-内酰胺酶的金黄色葡萄球菌分离株，新型1-氧杂化合物的活性低于老一代头孢菌素，其中头孢噻吩和头孢孟多最为有效。1-氧杂化合物对粪肠球菌分离株没有明显活性。在胰蛋白酶大豆肉汤和穆勒-欣顿肉汤中，随着肠杆菌科接种量增加，所研究的四种头孢菌素的活性均降低。在穆勒-欣顿肉汤中，随着接种量增加，新化合物对铜绿假单胞菌属的活性也降低，但在胰蛋白酶大豆肉汤中未出现这种情况。这些结果表明，这种新型1-氧杂化合物作为一种广谱抗生素可能具有很大前景，可能值得在人体中进行对照临床试验。
