We have demonstrated that physiologic concentrations of calcium antagonize in vitro the bactericidal activty of polymyxin, colistin, and gentamicin on Pseudomonas aeruginosa. Our findings indicate that these antibiotics may be much less effective in vivo than one would assume on the basis of in vitro activity. Efficacy of an antibiotic is demonstrated in three essential steps: (1) in vitro studies, (2) chemotherapy of infections in experimental animals, and (3) controlled chemotherapy trials in humans. A careful review indicates that efficacy of antibiotics of Pseudomonas infections has never been demonstrated in vivo. The few published studies of chemotherapy of experimental Pseudomonas infections are inadequate, and controlled trials in patients have not been done. We propose to determine the relative efficacy in vivo of colistin, polymyxin B, gentamicin, carbenicillin, and certain other antibiotics and major combinations of antibiotics in experimental Pseudomonas infections. Our study will provide the first adequate objective evaluation of in vivo activity of these antibiotics. Pseudomonas infections often occur in patients who have compromised defense mechanisms. Little is known about the interaction between antibiotics and host defense mechanisms. Antibiotics that are most active in the normal intact animal or patient may not be the most effective in a patient with diminished host resistance. Therefore the second phase of our proposed study will be to evaluate the relative efficacy of the most active antibiotics and combinations in experimental animals that have been treated with irradiation. BIBLIOGRAPHIC REFERENCES: Davis, S.D. Activity of Gentamicin, Tobramycin, Polymyxin B, and Colistimethate in Mouse Protection Tests with Pseudomonas aeruginosa. Antimicrob. Agents. Chemother. 8:50-53, 1975. Davis, S.D. Efficacy of Modified Human Immune Serum Globulin in the Treatment of Experimental Murine Infections with Seven Immunotypes of Pseudomonas aeruginosa. J. Infect. Dis. 131: 717-721, 1975.