Carolyn E. Hughes

In vitro activities of amphotericin B in combination with four antifungal agents and rifampin against Aspergillus spp.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility with a microtiter plate system in buffered yeast-nitrogen base and in buffered minimal essential medium. Isolates were tested against amphotericin B, flucytosine, rifampin, ketoconazole, ICI 153,066, and Bay n 7133 and against combinations of amphotericin B with each of the other five drugs. Combinations of amphotericin B and rifampin were the most active against all three species of Aspergillus. Flucytosine combined with amphotericin B produced little or no reduction of the MICs at which 90% of the strains were inhibited compared with amphotericin B alone. With one exception, the addition of ketoconazole, ICI 153,066, or Bay n 7133 to amphotericin B did not consistently alter the MICs. The addition of ICI 153,066 markedly increased the MICs of amphotericin B against the A. flavus isolates in both media. When the azoles were tested alone, Bay n 7133 was the most active against A. fumigatus, but was two- to fivefold less active against A. flavus. Ketoconazole was the most active azole against A. flavus.

Efficacy of routine fiberoptic endoscope cleaning and disinfection for killing Clostridium difficile.

We have evaluated a standard procedure for cleaning and disinfection of endoscopes for efficacy in eradicating a spore-forming bacterial organism, Clostridium difficile. Initially, 23 endoscopes were cultured for the presence of C. difficile after hanging in storage for at least 24 hours after cleaning and disinfection. All cultures were negative. Subsequently, endoscopes used in 15 patients who had stool cultures positive for C. difficile were cultured immediately after use and again after cleaning and disinfection with 2% alkaline glutaraldehyde for 5 min. Ten of 15 (67%) endoscopes were culture positive for C. difficile immediately after use. After cleaning and disinfection, all of the endoscopes were culture negative except one, which yielded two negative cultures and two cultures showing late growth of rare C. difficile colonies, but contamination could not be ruled out. In vitro exposure to 2% alkaline glutaraldehyde for 5 min resulted in 99% or greater killing of C. difficile spores. We conclude that cleaning and a minimum of 5 min of disinfection with 2% alkaline glutaraldehyde are likely to be effective in killing C. difficile vegetative organisms and spores on endoscopes.

Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four- or eightfold lower in the presence of 5 or 15 micrograms of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.

Irrelevance of growth phase with respect to the Bay n 7133 and ICI 153,066 susceptibilities of Candida albicans

Miconazole at 10(-5)-10(-4) M can kill Candida albicans in the logarithmic phase, but ketoconazole, the only established oral antifungal azole, cannot. Lethal potential in relation to growth phase was studied with Bay n 7133 and ICI 153,066, two recently developed oral triazoles. Each was strictly fungistatic regardless of phase of growth and was almost identical in effect to ketoconazole.

High-pressure liquid chromatographic assay of Bay n 7133 in human serum.

A high-pressure liquid chromatographic method that includes a Sep-Pak (Waters Associates, Inc., Milford , Mass.) preparation of human serum was employed for the quantitative assay of Bay n 7133. Drug levels of 0.1 to 20 micrograms/ml could be detected. No interference from amphotericin B was found in the chromatographic analysis of Bay n 7133.