The effect of some penicillins on Mycobacterium tuberculosis.
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Biomedical subjects
Publications and source records attributed to V Lorian.
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Thirty-seven per cent of 126 strains of Staphylococcus aureus, when tested on sheep blood-agar with sensitivity discs containing cephalothin, carbenicillin, oxacillin, penicillin, and cycloserine, produced rings of beta-hemolysis surrounding zones of inhibition of bacterial growth. Each strain capable of producing a ring of beta-hemolysis did so with at least two of the mentioned antibiotics. None of the other 15 antibiotics tested was associated with a ring of beta-hemolysis surrounding any of the zones of inhibition. It appears, therefore, that the beta-hemolysis observed was produced by certain strains of S. aureus only in association with certain antibiotics.
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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.
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Rifampin inhibited 20 strains of Mycobacterium tuberculosis in concentrations of 0.005 to 0.02 mug/ml in 7H-9 broth with Tween 80 and killed all or nearly all of the inoculum in four to eight times greater concentrations. In the same medium without Tween 80, as well as on 7H-10 agar, about 16 to 64 times these amounts were required to produce the same effect. Rifampin was also active against M. kansasii and some of the nonchromogenic mycobacteria. The incidence of mycobacterial cells resistant to rifampin within the cultures studied was in the range of one to four per 10(8) to 10(9) colony-forming units with concentrations of 4 to 125 mug of rifampin per ml. Only one of the Battey cultures and that of M. fortuitum yielded cells resistant to rifampin at 125 mug/ml but not at 500 mug/ml. The same strains yielded more than double that number of organisms resistant to streptomycin and up to 100 times more organisms resistant to isoniazid. All three drugs stopped the growth or reduced the mycobacterial population in growing cultures after contact for 24 to 48 hr. Complete inhibition of growth was produced by rifampin at 1.0 mug/ml in an average of 6 days and by streptomycin at 5.0 mug/ml in 3 days. After an average contact of 10.7 days with rifampin, five of seven strains resumed growth and all strains began regrowth after exposure to streptomycin for 9.4 days. The marked susceptibility of M. tuberculosis and of atypical mycobacteria to rifampin in vitro and the relatively low incidence of resistant mutants suggests that this agent may have clinical usefulness in the treatment of tuberculosis and some other mycobacterioses.
A group of 2,081 sputum specimens were planted on Direct Cord Reading Agar. A total of 330 (16%) of these specimens produced positive cultures, 312 strains of Mycobacterium tuberculosis and 18 strains of atypical mycobacteria. The strains of M. tuberculosis showed visible cords on plates in 283 (90.8%) of the isolates and no atypical mycobacteria showed cording. The specimens from the newly admitted patients yielded, in 12 days, 59% of their total positives; 97.6% of these strains, identified as M. tuberculosis with the standard methods recommended by the National Communicable Diseases Center, exhibited cording visible directly on the agar. It is suggested that, for practical purposes, a colony exhibiting cording could be tentatively reported as "M. tuberculosis to be confirmed."
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The antibacterial activity of erythromycin was markedly enhanced by alkalinization of the culture medium or urine within the clinical range (pH 6.0 to 8.2). This effect was demonstrated against recent isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., and Pseudomonas aeruginosa, as well as against Staphylococcus aureus and Streptococcus faecalis. The urine of normal volunteers was made alkaline by ingestion of sodium bicarbonate or acetazolamide (Diamox) during administration of 1.0 g of erythromycin every 8 hr; such urine was capable of inhibiting E. coli and K. pneumoniae even when diluted up to (in one instance) 128 times with broth of the same pH as the urine. Undiluted urine of the same subjects, without alkalinization, was seldom capable of inhibiting these organisms. The range of pH (6.6 to 8.6) over which the antibacterial effect was enhanced coincided with that over which there was decreasing ionization of a basic group.
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After 5 days of treatment, sputa were analyzed from 40 patients treated with sodium fusidate and 20 patients treated with naficillin. There was a significant decrease in the number of staphylococci, but no significant change in the other flora. The quantitative bacteriological analysis of sputum specimens proved to be a useful laboratory procedure for providing information on the in vivo effectiveness of specific antibacterial therapy in respiratory infections.
In a comparison of Lowenstein's medium with two agar media, 7H10 without and with the addition of Triton WR 1339, 4,100 sputa were planted on all three, yielding 803 (19.6%) positive cultures. The addition of Triton WR 1339 to the 7H10 medium made it possible to observe the cord formation directly on the isolation plates and did not alter, in any respect, the results obtained with the basic 7H10 medium. The agar media produced much earlier and more positive cultures than Lowenstein's medium. A greater number of cultures showed drug resistance on Lowenstein's medium as compared with the agar media.