Synergistic Antibacterial Activity of Ampicillin-Cloxacillin Mixtures Against Proteus morganii

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Synergistic antibacterial effects of mixtures of ampicillin and cloxacillin and induced penicillinases were investigated in 48 strains of Proteus. The serial tube dilution method was used to determine the minimal inhibitory concentration of ampicillin, cloxacillin, and 2:1 and 1:1 mixtures of ampicillin and cloxacillin. Production of penicillinases was determined by the cellulose acetate membrane method, with ampicillin, cloxacillin, mixtures of ampicillin and cloxacillin, penicillin G, and cephalothin as inducing agents and as substrates for penicillinase. Synergism occurred against P. morganii, but against no other species. The 1:1 ampicillin-cloxacillin combination was synergistic against 13 of 17 P. morganii strains; the 2:1 combination was synergistic against only 9 strains. Penicillinases, demonstrated in all species except P. mirabilis, hydrolyzed penicillin G and cephalothin. Although only P. vulgaris hydrolyzed ampicillin, no species of Proteus hydrolyzed cloxacillin or the ampicillin-cloxacillin mixtures. Penicillinases were, however, induced by ampicillin, cloxacillin, and the mixtures. There was no relationship between production of penicillinase and synergism with mixtures of ampicillin and cloxacillin.

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