Antibiotic Combinations and Resistance to Antibiotics: Penicillin-Erythromycin and Streptomycin-Erythromycin Combinations in vitro.

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Abstract
1. During 20 subcultures on blood agar containing increasing concentrations of penicillin or erythromycin each of 7 strains of Staphylococcus aureus increased markedly in resistance to the homologous antibiotic without affecting its sensitivity to the other agent. The combination of penicillin and erythromycin exerted slightly more than an additive effect on the parent strains. During 20 parallel subcultures on agar containing both antibiotics, the organisms retained their original sensitivity to penicillin alone but most of them increased slightly in resistance to the 2 agents in combination and to erythromycin alone, while one strain increased markedly in resistance to the latter agent. Coagulase production by these staphylococci remained unaltered following the exposures to these antibiotics except for 2 strains which lost this property after they became resistant to penicillin. 2. By serial transfers of several strains of staphylococci and of a strain of enterococcus in broth and/ or on the surface of blood agar containing increasing concentrations of erythromycin or streptomycin, high degrees of resistance developed against the homologous antibiotic, but cross-resistance to the other agent did not develop. Cross-resistance to neomycin was demonstrated in the strains of staphylococci which had increased in resistance to streptomycin following subcultures with the latter agent used either alone or in combination with erythromycin; such cross-resistance to neomycin did not occur in the strains which had become resistant to erythromycin following exposures to that antibiotic alone. The biological characteristics of the staphylococci, including coagulase production, remained unaltered following the development of resistance to either streptomycin or erythromycin, except for decreased production of pigment and less active growth of the resistant strains. The development of resistance to both erythromycin and streptomycin was delayed and depressed when the organisms were repeatedly subcultured in the combination of the 2 antibiotics.