Enhancement of Antimicrobial Activity of Penicillins and Other Antibiotics in Human Serum by Competitive Serum Binding Inhibitors.

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Abstract
Summary A series of compounds, many of which had been shown in dialysis studies to be effective in displacing penicillins from binding to human serum, have been tested for ability to enhance the antimicrobial activity of various penicillins and other antibiotics in the presence of 50% human serum. Enhanced antimicrobial activity in serum was shown in the case of sulfonamides to be only partially reversible by para-amino ben-zoic acid, suggesting that augmentation of penicillin activity was due to serum displacing effects as well as to the intrinsic antibacterial activity of sulfonamides. Evidence is presented that the “R” groups of penicillins are the most important determinants of binding to serum. The specificity of the penicillin binding sites was shown by the failure of displacing agents shown to be effective against the penicillin site(s), to effect binding of novobiocin and tetracyclines, and by the lack of effect of probenecid, known to be highly bound, to displace penicillins from serum. The author is indebted to Mrs. Louise Moore and Mrs. Ann Bugg for technical assistance, and to Dr. William S. Jordan, Jr., for review of the manuscript.