STRUCTURES AND BIOLOGICAL-ACTIVITIES OF TOBRAMYCIN-TICARCILLIN ADDUCTS

Aminoglycosides and penicillins chemically interact when they are comb ined in vitro or in vivo. The resulting adducts are considered to be b iologically inactive. The major adducts formed in the interaction betw een tobramycin and ticarcillin have been recently isolated in pure for m in our laboratory. On the basis of mass, infrared, and proton magnet ic resonance spectra, the major adducts appeared to be amides formed b y an attack of the beta-lactam carbonyl group of ticarcillin by an ami no group of tobramycin. All other moieties of ticarcillin were intact except that the beta-lactam ring was opened and was rotated by 120-130 degrees. The minimum inhibitory concentrations (MICs)of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 mu g/mL for Staph ylococcos aureus and Escherichia coil and 160.0, 0.5(i) and 8.0 mu g/m L for Pseudomonas aeruginosa. Thus, the major adducts possessed some a ntimicrobial activity, but not enough to be active in the treatment of infections: As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some crossreactivity in the assay of tobramyc in. However, it was insufficient to cause Significant error in the mea surement of tobramycin in human serum.