Why this was so striking to me? Up to this point, I was stamping plates with about 32 microorganisms, 32 different strains of B. fragilis and they're growing up at very high concentrations of all the new experimental penicillins plus combinations of beta lactamase inhibitors that were made in the project. I finally got this compound. I stamped the organisms on a plate containing the compound. Of course, it was a mixture of the compound and penicillin. The results were so striking that I thought I didn't stamp the plate because there was nothing growing on that plate! We don't get many chances to say, "Wow! Eureka!" Well, I didn't say eureka but certainly wow! I looked at this thing and I said, "That's right. We've got a compound that potentially could restore the activity ot penicillin, resulting in a combination that might be extremely effective against an anaerobic infection due to B. fragilis." Sure enough, it went on to be known as Unasyn, a very well known drug that has been used to saved a lot of lives and cure nasty infections following surgery.
By the way, in addition to making money, of course, for pharmaceutical firms, it is very satisfying when we can take something like this and we see clinical response, knowing that lives are being saved. In this particular example, we were also very fortunate to get this clinical response. I'm not going to say but very little about pharmacokinetics (the study of serum levels of active compound following dosing). But even though the clinical picture looked very good, we were just lucky that when you injected sublactam and the penicillin, the serum peaks (maximum concentration achieved in serum) overlapped. If they didn't overlap and we didn't get this type of ratio which we needed to be effective, we might have had to inject one drug at one time and the other drug later and try to find out just where they do overlap. We were lucky with this one.
Here is just another graphic representation. This is ampicillin over here plus this sublactam that blocks the enzyme. Here is the concentration along this bar. We can see practically everything is 100% inhibited by the time we reach 3.1 of the ampicillin or the sublactam. I can't even read that. But it's the combination--well, oh, it's 1:1. This is just a graphic representation of the drug by itself. It's all these organisms here when it fails because once you get above that level, you can't really go any higher and achieve higher blood levels with penicillin.
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