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Biomedical subjects

E R Garrett

Publications and source records attributed to E R Garrett.

At least 73 records · Page 4Linked to original sources

Microbial kinetics and dependencies of individual and combined antibiotic inhibitors of protein biosynthesis.

The generation rate constants for the steady-state growth of antibiotic-inhibited Escherichia coli have the same formal dependency on concentration for deoxylincomycin, lincomycin (phase I), erythromycin, clindamycin, and U24729A. They may be kinetically classified as a group A, in which the first three compounds comprise a subgroup A(1) and the latter two a subgroup A(2). Generation rate constants initially decrease linearly with concentration but asymptotically approach zero at higher concentrations. With tetracycline or chloramphenicol, the generation rate decreases linearly with all concentrations, and these compounds may be kinetically classified as group B. Combining an antibiotic from group A with one from group B gives a response equal to that obtained with equivalent amounts of each antibiotic alone, and there are no significant effects from the order of antibiotic addition. However, combinations of an A(1) with an A(2) antibiotic are antagonistic, and there are significant effects from the order of addition. The dependencies of generation rate constants in the presence of these antibiotics can be rationalized by a receptor site model that considers varying degrees of the rate of drug transfer and drug inactivation in the organism.

Anti-Bacterial Agents↗

Effect of novobiocin and its combination with tetracycline, chloramphenicol, erythromycin, and lincomycin on the microbial generation of Escherichia coli.

Inhibition of the steady-state generation of Escherichia coli by the bacteriostatic antibiotic novobiocin is linearly related to drug concentration in the range of 0 to 30 mug/ml. Increased cell sizes result because the drug inhibits cell division. The generation rate dependence on drug concentration depends on the nonionized fraction of novobiocin and is invariant with inoculum size or medium composition. However, the antibacterial activity of novobiocin decreases as the concentration of nutrients and Mg(2+) increases, although the inhibitory action of novobiocin on generation rate remains unchanged for concentrations of Mg(2+) above 8.1 x 10(-4) M. Novobiocin is synergistic in combinations with tetracycline in broth, but not when the Mg(2+) was maintained at 4.05 x 10(-3) M. Combinations of novobiocin with the 50S ribosomal subunit inhibitors chloramphenicol, erythromycin, or lincomycin are antagonistic, and the degree of growth inhibition is determined only by that component of the binary combination that would have the greater potency if it were acting alone.

Cell Division↗