Bactericidal Concentrations Of Penicillin Research Articles

Penicillin therapy of experimental endocarditis induced by tolerant Streptococcus sanguis and nontolerant Streptococcus mitis.

The response of tolerant Streptococcus sanguis and nontolerant Streptococcus mitis infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 mug/ml, respectively, for S. mitis and 0.05 and 6.2 mug/ml, respectively, for S. sanguis. Time-kill studies done in vitro with penicillin concentrations of 2 and 20 mug/ml demonstrated minimal killing of the tolerant strain, with a 3 log difference in survival between the two strains after 24 and 48 h. Both strains produced endocarditis with comparable bacterial densities on the valvular vegetations. Rabbits were treated with procaine penicillin G in two dosage regimens, 80,000 or 5,000 U/kg given every 8 h. There was no difference between bacterial densities in valvular vegetations removed from rabbits infected with either strain after 2, 4, or 6 days of treatment with the high-dose regimen (serum penicillin concentration at 0.5 h, 9.4 mug/ml), despite the fact that serum bactericidal activity against the tolerant strain at 0.5 h was minimal. With the low-dose penicillin regimen (serum concentration at 0.5 h, 2.5 mug/ml), therapy was significantly less effective in the tolerant group only after 6 days of treatment. Similar results were obtained when penicillin was administered in low and high doses to prevent infection. In this animal model of infection, penicillin tolerance was associated with a diminished response to penicillin therapy only when the dose was severely restricted. In the high-dose regimen, there was no difference in the response to penicillin therapy between animals infected with either strain, despite the presence of only minimal serum bactericidal activity in the rabbits infected with the tolerant strain.

Importance of Medium in Demonstrating Penicillin Tolerance by Group B Streptococci

A total of 30 clinical isolates of group B streptococci were studied for penicillin tolerance in vitro. Minimal inhibitory and bactericidal concentrations of penicillin were determined simultaneously in three test media which have been used for group B streptococci, tryptose phosphate, Mueller-Hinton, and Todd-Hewitt broths, using a logarithmic-phase inoculum of 10(5) colony-forming units per ml. Minimal inhibitory concentrations in the three media did not differ significantly. However, minimal bactericidal concentrations were significantly higher in tryptose phosphate broth (mean, 1.04 mug/ml) than in Mueller-Hinton broth (0.22 mug/ml) or Todd-Hewitt broth (0.15 mug/ml). Similarly, ratios of minimal bactericidal to minimal inhibitory concentrations were significantly greater in tryptose phosphate broth than in Mueller-Hinton or Todd-Hewitt broth. After incubation in tryptose phosphate broth for an additional 24 h, the minimal bactericidal concentration consistently fell to levels which were only twice or equal to the minimal inhibitory concentration. This study illustrates the importance of the medium in the demonstration of penicillin tolerance and of controlling laboratory variables in the susceptibility testing of group B streptococci with penicillin.

Trimodal response of Escherichia coli and Proteus mirabilis to penicillins.

IT has been generally believed that penicillins act on Gram-negative bacilli by interfering with cell wall synthesis leading to the release of spheroplasts which then succumb to osmotic damage. Such damage is usually fatal although in conditions of suitably high osmolarity the spheroplast phenomenon is known to be reversible1. Using turbidimetric methods supported by morphological studies in the scanning electron microscope, we have recently demonstrated that Escherichia coli and Proteus mirabilis show a variety of responses to penicillins which cannot be satisfactorily explained on the basis simply of the emergence and subsequent osmotic destruction of spheroplasts2,3. With the high bacterial population densities used, large numbers of “persisters” (organisms which survive exposure to bactericidal concentrations of penicillin although their progeny remain fully sensitive4) could be recovered after prolonged exposure to penicillins, and it seemed that this survival resulted from yet another response to the agents. In this investigation we have extended our studies and have attempted to elucidate the persister phenomenon.

PENICILLIN PLASMA CONCENTRATIONS

Although there is considerable difference of opinion regarding the therapeutic efficacy of bactericidal concentrations of penicillin for a brief time as opposed to the maintenance of bacteriostatic concentrations for prolonged periods, it is not within the province of this paper to discuss the relative merits of these two approaches to penicillin therapy. Suffice it to say that there are authoritative proponents of both methods of treatment and there are good reasons for wishing to achieve very high levels, amounts measured in whole units of penicillin per cubic centimeter, and for maintenance of lower concentrations of a few hundredths to a few tenths of a unit per cubic centimeter for prolonged periods. It is the purpose of this paper to show how both of these requirements of therapy can be achieved. ORAL ADMINISTRATION OF CARINAMIDE WITH PENICILLIN GIVEN INTRAMUSCULARLY Penicillin is rapidly excreted by the

The Assimilation of Amino-acids by Bacteria: 5. The Action of Penicillin in Preventing the Assimilation of Glutamic Acid by Staphylococcus aureus

SUMMARY: The effect on glutamic acid assimilation of the addition of penicillin to growing cultures of Staphylococcus aureus is described. When Staph, aureus is grown in media containing glutamic acid this substance accumulates in steadily increasing concentration in the cells. The addition of penicillin to the medium is followed after an interval by rapidly decreasing concentration of glutamic acid within the cells. The assimilation of glutamic acid by normal washed cells is not affected by penicillin in high concentration. The assimilation of glutamic acid by cells which have grown in the presence of penicillin is impaired and may be completely inhibited. Complete inhibition of assimilation is brought about by bactericidal concentrations of penicillin, low concentrations requiring a longer time to become completely effective than high ones. The loss of assimilatory power can be correlated with loss of viability. Comparison of the general properties of normal and penicillin-inactivated cells show that the respiration, glucose oxidation, glucose fermentation and lysine assimilation of the latter are normal. The internal metabolism of glutamic acid is normal in penicillin-treated cells, but, since the passage of glutamic acid across the cell wall is blocked, is limited by the existing internal concentration.