In vitro studies with miconazole and miconazole nitrate.
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Biomedical subjects
Publications and source records attributed to A Espinel-Ingroff.
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A radial diffusion bioassay for miconazole, which employs Candida stellatoidea as the indicator organism, is described. Results from three patients treated with the drug are presented.
The availability of active amphotericin B after filtration of the intravenous form of the drug through in-line filters was examined. Filtration through circular filters of 25-mm diameter and 0.45-micronm pore size resulted in little loss of active drug, although a marked decrease in flow occurred with time. Filtration through either circular or cylindrical filters with 0.22-micronm pores resulted both in significant losses of active drug and in marked decreases in flow. Thus, membrane filters of 0.22-micronm pore size are not suitable for use in intravenous administration of amphotericin B. The use of filters of 0.45-micronm pore size is appropriate only in situations in which decreased flow is acceptable.
A new method for the determination of minimal inhibitory and fungicidal concentrations of antifungal agents for filamentous fungi is described. 5-Fluorocytosine (5-FC) was used as a representative agent and was tested against the following genera: Allescheria, Aspergillus, Cladosporium, Fonsecaea, and Phialophora. 5-FC was found to be inhibitory but not fungicidal for many of the fungi tested, including eight of clinical origin.
The stability of solutions of amphotericin B as prepared for intravenous use in glass and polyvinyl chloride plastic (PVC) containers was studied. Four conditions were tested: contained within glass and exposed to light; contained in glass and shielded from light; contained in PVC and exposed to light; contained in PVC and shielded from light. Bioassays were performed on specimens collected from the containers periodically during 24 hours. Results of the bioassays revealed no significant loss of activity under any of the test conditions.
Variations in molecular karyotype and fluconazole susceptibility of serial yeast isolates from the oral cavities of nine patients with AIDS receiving fluconazole for single or multiple episodes of oropharyngeal candidiasis were monitored. Multiple yeast species were isolated from the initial oral specimens in six patients. Molecular karyotyping identified at least eight different DNA subtypes of C. albicans, at least eight of T. glabrata and only one DNA subtype each of C. krusei, C. tropicalis and C. parapsilosis. Among isolates of T. glabrata, fluconazole MICs in each patient were consistently within one or two dilutions, regardless of strain variations. Similarly, among five patients monitored during one course of therapy, the MICs of fluconazole of C. albicans isolates of either the same or different DNA subtypes remained within two dilutions. However, increases in MICs of fluconazole of C. albicans were observed in four patients who received two or more courses of fluconazole, three of whom had the same DNA subtype and one of whom changed from one DNA subtype to another.
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In vitro susceptibilities of 290 isolates of Candida spp to fluconazole were evaluated by a new NCCLS M44-P agar disk diffusion method that was read and interpreted automatically by the BIOMIC image-analysis plate reader system. Disk test results were compared to results obtained by a modified NCCLS M27-A broth microdilution method using RPMI-1640 supplemented with 2% dextrose. Overall agreement between both methods was 90.0%. Category agreement between the broth and disk test results for susceptible, susceptible dose-dependent and resistant disk results were 99.6%, 19.05% and 52.17%, respectively. No very major discrepancies, 1.03% major discrepancies, and 8.97% minor discrepancies were observed between results of the two test methods. This analysis suggests that results from both methods correlate highly for Candida strains susceptible to fluconazole. The lower agreement between the two methods for resistant and susceptible dose-dependent isolates was due to strains near or on that breakpoint, different media (Mueller-Hinton vs RPMI), agar vs broth, 80% vs 50% endpoints, and trailing growth near the endpoints.