Abstract
Summary and Conclusions
1. Variants with high degrees of resistance to erythromycin were not isolated from small volumes of cultures of erythromycin-sensitive bacteria which had not previously been exposed to that antibiotic. 2. When cultures of erythromycin-sensitive staphylococci (which were completely inhibited by 0.4 μg/ml in the plate-dilution test) were grown from a 10% inoculum in broth in the presence of 16 |mUg/ml of erythromycin, strains of varying resistance could be recovered after 48 hours; these required concentrations of erythromycin ranging from 0.2 to 25 |mUg/ml for complete inhibition. 3. By repeated subcultures of erythromycin-sensitive bacteria on blood agar containing graded concentrations of erythromycin it was possible to obtain strains of increased resistance to this antibiotic. The rate at which this resistance increased varied markedly with the strain. Several strains of Staphylococcus aureus, an enterococcus and a pneumococcus each increased more than 512-fold in from 3 to 12 such subcultures. Strains of only moderately increased resistance were obtained after 20 similar subcultures of a strain of hemolytic streptococcus and one of Streptococcus viridans. 4. The strains of increased resistance resulting from repeated subcultures on the erythromycin-containing agar retained that resistance after 10 further subcultures in antibiotic-free broth. 5. Strains of increased resistance to erythromycin derived by repeated subcultures in that antibiotic were almost invariably similar to their respective parent strains in their sensitivity to 8 other antibiotics; however, an erythromycin-resistant strain of type 3 pneumococcus had apparently increased in sensitivity to neomycin following its repeated subcultures in erythromycin. 6. Staphylococcal strains of markedly increased resistance to erythromycin were obtained from blood cultures of 2 patients with endocarditis following 7-10 days of treatment with this antibiotic. 7. The colonial, morphologic and biochemical characteristics of the erythromycin-resistant strains obtained by repeated subcultures in erythromycin-containing media resembled those of the respective parent strains from which they were derived in almost every instance. The strains of Staphylococcus aureus, however, lost their ability to produce coagulase and exhibited other changes in their biochemical properties following their repeated subcultures in the presence of erythromycin. Similar changes were not observed in the 2 strains of Staphylococcus aureus which had apparently become resistant during erythromycin therapy.
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