The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration.Rapamycin cured systemic candidosis in mice: PD50 s. c. was 9.5 mg/kg; PDso p. o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PDso values of <0.25 mg and >4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91 % cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment.
The antibiotics, polymyxin A B C D and E, have been described in the recent literature. Their antibacterial spectra are similar. They differ from one another in amino acid content. It is the purpose of this presentation to describe our studies of the antibacterial activity, pharmacology, untoward reactions, and clinical experience with polymyxin B and polymyxin E.5
IN VITRO ACTIONWe found that the susceptibility to polymyxin of 78 strains of ten different genera by the tube dilution test (Table I) is marked against Salmonella, Shigella, Klebsiella, microorganisms of the coli aerogenes groups, and most importantly, Pseudomonas. Brucella and many staphylococci are moderately sensitive, while Proteus and hemolytic streptococci are refractory. It is of interest that a strain of Pseudomonas, which developed high resistance to streptomycin in three daily transfers, did not become resistant to polymyxin after 27 transfers. Size of inoculum and human serum reduced but slightly polymyxin activity. The concentration of polymyxin required to inhibit Klebsiella and Pseudomonas is not reduced significantly by the addition of subinhibitory amounts of streptomycin, aureomycin, sulfadiazine or penicillin, either singly or in several combinations. Polymyxin antagonizes the cumulative streptomycinpenicillin action on Proteus.
SUMMARYA bacteriological study was made of blood specimens taken repeatedly during a 2-year period from a child with subacute bacterial endocarditis who received intensive treatment with antibiotics. The conventional bacillary form of Corynebacterium sp. was present in the blood and bone marrow of the patient before the beginning of antibiotic therapy and on occasions when the administration of antibiotics was suspended. These were the periods when the patient showed overt symptoms of clinical illness. When antibiotic therapy was adequate to produce clinical remission of symptoms, the infecting organism was not eradicated, but persisted in the blood in a small granule-like form that could be demonstrated and cultured only by highly specialized techniques. The cultural procedures required to bring about reversion of the granule-like form to the conventional bacillary form and the morphology of the various transitional forms that the organism assumed during the reversion process are described and illustrated.
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