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Management.

Abstract

The management of invasive fungal infection utilizes a variable multidisciplinary approach involving antifungals, appropriate surgery and immuno-correction. Conventional amphotericin B has been the mainstay of treatment but newer pathogens and poor outcomes has led to new formulations of this drug as well as to new and novel antifungals.

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BibTeXRIS

M Ellis, M Richardson. 2000. Management.. https://doi.org/10.12968/hosp.2000.61.9.1417

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Multi-Omics Analysis of Experimentally Evolved Candida auris Isolates Reveals Modulation of Sterols, Sphingolipids, and Oxidative Stress in Acquired Amphotericin B Resistance.

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Amphotericin B↗

Effects of membrane partitioning and other physical chemical properties on the apparent potency of "membrane active" compounds evaluated using red blood cell lysis assays.

The membrane-destabilizing properties of Amphotericin B and Zwittergent were used as benchmark compounds for examining in detail their membrane-altering effects in a series of human red blood cell lysis assays. The procedures included examining dose responses and the effects of different cell concentrations on potency in rbc lysis assays. In order to enhance detection of subtle membrane effects, we also used a range of NaCl concentrations to osmotically stress the rbc's. Using the benchmark compounds, a set of conditions was developed for examination of subtle membrane effects that may be applied to series of compounds with suspected membrane-perturbation activity. A group of experiments was defined that allow detection of the most important membrane-modifying behaviors among a diverse group of compounds. From an initial screen of bacterial growth inhibition over 150 compounds were examined for membrane-altering properties using the limited experimental protocols developed from the benchmark compounds. Several dose-response patterns were observed as useful for classifying compounds based on their tendency to alter membrane integrity and to partition into the lipids of membranes, as well as their propensity to form aggregates or precipitates. The methods may prove generally useful for distinguishing compounds whose primary activity is membrane destabilization from more interesting and useful pharmacological mechanisms of action.

Amphotericin B↗