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Biomedical subjects

S M Heman-Ackah

Publications and source records attributed to S M Heman-Ackah.

10 recordsLinked to original sources
PubMed1976

Comparison of tetracycline action on Staphylococcus aureus and Escherichia coli by microbial kinetics.

Cultures of tetracycline-treated Staphylococcus aureus exhibited monophasic steady-state growth curves similar to that observed for tetracycline-treated Escherichia coli. Apparent growth rate constants of the respective drug-treated cultures showed the same formal dependence on drug concentration, which was linear at a low concentration but asymptotically approached zero at higher concentration levels and implied the saturation of a limited number of receptor sites engaged in microbial protein synthesis. The relative potency of tetracycline action of S. aureus/E. coli was 6.50:1 at 37.5 degrees C and pH 7.05. This is attributed to relative differences in drug permeation and/or binding affinity for biophase receptors in the respective organisms. It is concluded from kinetic dependencies of growth inhibition of the cultures that tetracycline has the same mode of action on S. aureus and E. coli. It is bacteriostatic at concentrations below the minimal inhibitory concentration level but bactericidal at the higher concentration levels.

Culture Media↗
PubMed1975

Microbial kinetics of drug action against gram-positive and gram-negative organisms. II: Effect of clindamycin on Staphylococcus aureus and Escherichia coli.

Clindamycin-affected Staphylococcus aureus cultures show biphasic steady-state generation curves. An initial (phase I) generation of the clindamycin-affected Staph. aureus is followed by an ultimate (phase II) generation at the same dose level. The phase I apparent generation rate constant is greater than the phase II apparent generation rate constant and suggests the development of resistant Staph. aureus mutants to clindamycin action after a finite period of drug-bacteria contact at any subcompletely inhibitory concentration level. It is rationalized that the increased resistance to drug action in mutant strains is due to a comparatively reduced ribosomal binding affinity for clindamycin. In contrast, clindamycin-affected Escherichia coli cultures show monophasic steady-state generation curves at all concentration levels; E. coli cultures do not develop resistance to clindamycin action. The dependence of the apparent generation rate constant on drug concentration yields a sigmoidal curve, which is coincident by a potency factor for the phase I and phase II generations of clindamycin-affected Staph. aureus and suggests a common mechanism of action for both generation phases. That of clindamycin-affected E. coli yields an asymptote curve, which indicates a different mechanism of action. Clindamycin possesses both a bacteriostatic and a bactericidal action on initial and mutant resistant strains of Staph. aureus, whereas its action on E. coli is only bacteriostatic. Consequently, clindamycin has a minimum inhibitory concentration (MIC) against E. coli that is about 1000 times the MIC value against Staph. aureus at 37.5 degrees. The effect of pH changes in broth media on generation inhibition of both Staph. aureus and E. coli by clindamycin action indicates that the unprotonated fraction of drug concentration contributes to the activity, possibly because of its ready penetration through cell membranes.

Clindamycin↗
PubMed1975

Microbial kinetics of drug action against gram-positive and gram-negative organisms. III: Effect of lincomycin and clindamycin combinations on Staphylococcus aureus and Escherichia coli.

The functional dependencies of apparent first-order generation rate constants kapp, of drug-affected cultures on drug concentrations indicate that lincomycin and clindamycin possess the same mechanism of action, which is bacteriostatic, against Staphylococcus aureus. Clindamycin also possesses another mechanism of action, which is bactericidal, at high concentration levels. However, clindamycin possesses only one of the two mechanisms of lincomycin action, which is bacteriostatic, against Escherichia coli. The relative potency of action of a clindamycin-lincomycin combination against Staph. aureus is variable, and the effective ratio ranges between 5:1 and 9:1; the effective ratio against E. coli is fixed at 6:1 over a wide concentration range. This difference is attributed to differences in bioavailability and/or binding characteristics of the drugs for bioreceptors, as a consequence of structural modifications in the drug molecules, and to differences in modes of action in the respective organisms. Mixtures containing equipotent fractions of clindamycin and lincomycin show "equivalence" or "indifference" of effects on Staph. aureus. The combined action of the mixtures can be quantitatively predicted from the separate dose-response curves of either component drug alone. Therefore, it is concluded that clindamycin and lincomycin may bind to the same receptor site that is engaged in microbial protein synthesis to inhibit the generation of Staph. aureus. However, combinations of clindamycin and lincomycin are less active than the a priori equipotent concentration of either drug alone in their action against E. coli, demonstrating unequivocally an antagonism of effects. Furthermore, the degree of antagonism is dependent on the order of addition of the drugs, which is attributed to the possibility that clindamycin and lincomycin bind differently on active and allosteric loci of the same receptor site functionally engaged in protein synthesis in E. coli. A rational approach to the quantification and prediction of combined antibiotic action must, therefore, be based not only on the kinetics and mechanisms of action as well as on the dose-response relationship over a wide concentration range for the separate antibiotics but also on the strain and species of the test organism.

Clindamycin↗
PubMed1973

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↗