Structures and biological activities of tobramycin‐ticarcillin adducts

Aminoglycosides and penicillins chemically interact when they are combined in vitro or in vivo. The resulting adducts are considered to be biologically inactive. The major adducts formed in the interaction between tobramycin and ticarcillin have been recently isolated in pure form in our laboratory. On the basis of mass, infrared, and proton magnetic resonance spectra, the major adducts appeared to be amides formed by an attack of the B‐lactam carbonyl group of ticarcillin by an amino group of tobramycin. All other moieties of ticarcillin were intact except that the β‐lactam ring was opened and was rotated by 120–130°. The minimum inhibitory concentrations (MICs) of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 μg/mL for Staphylococcus aureus and Escherichia coli, and 160.0, 0.5, and 8.0 μg/mL for Pseudomonas aeruginosa. Thus, the major adducts possessed some antimicrobial activity, but not enough to be active in the treatment of infections. As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some cross‐reactivity in the assay of tobramycin. However, it was insufficient to cause significant error in the measurement of tobramycin in human serum.