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Pneumonia caused by Pseudomonas aeruginosa occurs frequently in critically ill patients and is associated with a mortality rate of 70 per cent. An aerosol of polymyxin B was administered (2.5 mg per kilogram per day) to the upper airways of 292 patients in a respiratory-surgical intensive-care unit during a seven-month period, in an attempt to prevent Ps. aeruginosa pneumonia. Although only one of the patients studied acquired pneumonia due to Ps. aeruginosa, 10 others acquired pneumonia caused by a polymysinx-resistant organism. Seven pneumonias were caused by organisms not frequently pathogenic to man (flavobacteria, serratia and Streptococcus faecalis). The mortality rate for acquired pneumonia in this study, 64 per cent, is greater than that in previous studies in which either no polymyxin or cyclic polymyxin therapy was used. Continuous use of polymyxin B aerosol appears to be a dangerous form of therapy.

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The three imidazole antimycotics clotrimazole, miconazole, and ketoconazole all inhibit the demethylation of lanosterol to ergosterol, resulting in inhibition of growth of Saccharomyces cerevisiae; this is a fungistatic action. At higher concentrations clotrimazole and miconazole are fungicidal, whereas ketoconazole is not. The fungicidal action reflects direct membrane damage by the imidazoles. Evidence for this is that ketoconazole is markedly less active than the other imidazoles in its ability to allow methylene blue entry into cells and to disrupt liposome model membranes. The possible clinical significance of these findings is discussed.

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The mechanism of the antifungal action of the imidazole antimycotics, miconazole ano clotrimazole, on Saccharomyces cerevisiae was explored. When grown aerobically both drugs were fungistatic at low concentrations and fungicidal at high concentrations. When grown anaerobically the fungistatic effect was not seen, but killing still occurred at high concentrations. The fungistatic effect correlated with inhibition of ergosterol synthesis and elevated lanosterol/ergosterol ratios in the organisms. The fungicidal effect involved rapid membrane damage and was unrelated to the imidazole-induced block in ergosterol synthesis. These agents each have 2 distinct antifungal actions.