Ingo Haller

Mode of action of clotrimazole: implications for therapy.

Ergosterol is an essential constituent of the fungal cytoplasmic membrane. Clotrimazole and other azoles interfere with the ergosterol biosynthesis in a concentration-dependent fashion. Although low concentrations exhibit only a partially inhibitory effect, high concentrations may completely block ergosterol synthesis. Reduction of fungal growth and inhibition of growth and fungicidal action during prolonged incubation are the corresponding effects at the cellular level that are a consequence of ergosterol depletion. The inoculum effect, the influence of the incubation period, and the influence of nutrient media, three factors that often complicate susceptibility testing in vitro, can also be explained by the mode of action of azole compounds. Another interesting characteristic of azole antifungals was revealed by the observation that hyphae and pseudomycelia of Candida albicans are much more susceptible to azoles than are yeast cells. Even 1% of the minimum inhibitory concentration of clotrimazole may totally inhibit mycelial growth in vitro. This may be of clinical importance, since germination was reported to enhance adherence of C. albicans to buccal and vaginal epithelial cells.

Zur Resistenzlage von Staphylococcus aureus: β-Laktamasebildung und Empfindlichkeit gegenüber verschiedenen penicillinen sowie erythromycin

Abstract The actual resistance of Staphylococcus aureus from different clinics in Bielefeld was examined on the basis of 155 strains freshly isolated from clinical specimens during a period of two months. Sensitivity of these strains was assessed by minimum inhibitory concentrations (MICs) as determined by agar dilution method. As expected oxacillin proved to be the most effective compound according to its stability to β-lactamases. Ampicillin and amoxicillin were nearly as active as penicillin G, while propicillin exhibited a higher activity than penicillin G against those strains which were moderately sensitive to penicillin G. MICs of erythromycin were similar to those of propicillin and most of the highly penicillin resistant strains proved to be resistant to erythromycin too. When comparing the acylureidopenicillins and ticarcillin nearly identical MIC values resulted for azlocillin, mezlocillin and piperacillin; ticarcillin was found to be slightly less active. The qualitative assay for β-lactamase activity performed after induction with methicillin demonstrated strong correlation between presence or absence of β-lactamases and sensitivity of the bacteria to penicillin G. β-lactamase activity could be found in almost all strains with MIC ≧ 0.25 μg/ml for penicillin G. These results are discussed with respect to the recommendations for susceptibility testing.