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Biomedical subjects

L D Sabath

Publications and source records attributed to L D Sabath.

At least 73 records · Page 4Linked to original sources

Rapid microassays for clindamycin and gentamicin when present together and the effect of pH and of each on the antibacterial activity of the other.

Gentamicin was measured in the presence of clindamycin by using as the assay organism a strain of Staphylococcus aureus that was resistant to clindamycin; clindamycin was measured in the presence of gentamicin by using Clostridium perfringens as the assay organism. Both assays were in agar diffusion systems, were rapid (2 to 4 h), and had errors of less than 10%. Neither antibiotic antagonized or synergized with the other against a variety of organisms. The pK of clindamycin was 7.3, and the pK of gentamicin was 8.2. Gentamicin was 100 or more times as active in alkaline medium against both gram-positive and gram-negative organisms, but clindamycin showed a striking pH effect on activity only with gram-positive organisms.

Anti-Bacterial Agents↗

Susceptibility of Nocardia asteroides to 45 antimicrobial agents in vitro.

A method for preparing uniformly dispersed cultures of Nocardia asteroides for use in tests for susceptibility to antimicrobial agents is described. The minimal inhibiting concentration (MIC) of 45 agents for cultures thus prepared was determined with the use of a replica-inoculating apparatus. Minocycline at a concentration of 3.1 mug or less/ml inhibited 90% of the strains tested, and all were inhibited by 6.3 mug/ml. An erythromycin concentration of 0.8 mug or less/ml inhibited 40% of the strains, but the MIC for most of the others was > 100 mug/ml. The other agents were generally less active. Chemically related analogues varied in activity to different degrees. Also, the MIC of each antibiotic against different strains generally varied over a wide range. Sulfonamides and trimethoprim were not active against most strains in the method used. The size of the inoculum markedly affected the MIC of sulfonamides and had variable effects on other agents. Marked synergy of erythromycin with ampicillin was demonstrated for nearly all strains tested.

Anti-Bacterial Agents↗

Suppression of intrinsic resistance to methicillin and other penicillins in Staphylococcus aureus.

The pH of the medium in which staphylococcal susceptibility to penicillins was determined was found to make a profound difference (128- to 8,000-fold) in the expression of "intrinsic" resistance, whereas beta-lactamase-mediated resistance was only slightly affected by pH; methicillin-resistant staphylococci that are beta-lactamase-negative are models of pure intrinsic resistance, and the common beta-lactamase-producing organisms (methicillin-susceptible) are examples of pure beta-lactamase-mediated resistance. Methicillin-resistant staphylococci were unable to express their resistance at pH 5.2. However, growth of methicillin-resistant organisms in acid (pH 5.2) medium, followed by susceptibility testing at pH 7.4, showed no elimination of the genotype for intrinsic resistance, indicating that the pH effect was due to suppression, rather than to elimination of the gene determining the intrinsic resistance. These pH changes had little effect on the susceptibility of staphylococci that possessed neither intrinsic resistance nor beta-lactamase-mediated resistance. Thus, the suppression of "intrinsic" resistance was highly specific, and probably not the result of a change in ionization of the antibiotic, which would have been expected to affect all cells essentially equally. It is unlikely that foci of inflammation in man become sufficiently acid to suppress methicillin resistance of the staphylococci causing infection and inflammation.

Culture Media↗

Effect of pH on the activity of erythromycin against 500 isolates of gram-negative bacilli.

Erythromycin was found to be a more effective inhibitor of gram-negative bacilli in alkaline medium than in neutral or acid medium. A definite effect was noted with all of 500 recent clinical isolates of Escherichia coli, Klebsiella-Enterobacter, Pseudomonas aeruginosa, and Proteus mirabilis studied, but it was most striking with E. coli. At pH 8.5 all strains, except for 14% of those of P. mirabilis, were inhibited by concentrations of erythromycin readily achieved in urine with common therapeutic doses.

Bacteriuria↗