Factors which influence synergism by neomycin and oxytetracycline

Six strains of enteropathogenic gram-negative bacteria were tested for susceptibility to neomycin or oxytetracycline alone and combined in fixed ratios. The minimal inhibitory concentration for the combination was less than one-half of that expected if the antibiotic activities were simply additive. Neomycin alone was more effective against bacteria multiplying in the presence of abundant oxygen, whereas oxytetracycline alone was more effective against bacteria multiplying in relatively anaerobic environments; when combined, the antibiotics complemented each other by their opposing optima for activity. Oxygen concentration, pH, and neomycin activity are related, and the depression of acid production by oxytetracycline is believed to be partially responsible for the synergistic activity of this pair of antibiotics.