PubMed · 9097377
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
G A Sarosi. 1997. Cryptococcal pneumonia.. https://pubmed.ncbi.nlm.nih.gov/9097377/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Clinical isolates of Candida auris show a high prevalence of resistance to Amphotericin B (AmB)-an uncommon trait in most Candida species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in C. auris laboratory strains but are rarely seen in clinical isolates. In this study, we experimentally evolved two drug-susceptible Clade II isolates of C. auris to develop AmB resistance. The evolved strains displayed a four to eight fold increase in MIC50 compared to the parental cells. We analyzed changes in their karyotype, genome, lipidome, and transcriptome associated with this acquired resistance. In one lineage, AOX2 was upregulated, and its deletion reversed the AmB resistance phenotype. The aox2Δ mutant also failed to evolve AmB resistance under experimental conditions. In the same lineage, restoring the UPC2 S332R and RTG3 S101T mutations to the wild-type allele restored AmB susceptibility. In another lineage, the ergosterol and sphingolipid pathways were observed to play a critical role, and upregulation of the ERG genes elevated the total sterol content, while significant downregulation of HSX11 (glucosylceramide synthase) resulted in lower levels of glucosylceramides. To our knowledge, this study is the first to show that AmB resistance in C. auris can be acquired through mechanisms both dependent on or independent of sterol content modulation, highlighting Aox2 and Upc2 as key regulators of amphotericin resistance.
Selective decontamination of the digestive tract (SDD) is a strategy designed to prevent or minimize the impact of infections by potentially pathogenic micro-organisms in critically ill patients requiring long-term mechanical ventilation. SDD is a four-component protocol to control the three types of infections occurring in intensive care patients: (a) a parenteral antibiotic, cefotaxime, for a few days to prevent primary endogenous infections that generally occur 'early'; (b) the topical antimicrobial drugs colistine (polymyxin E), tobramycin and amphotericin B (together: PTA) used throughout the stay in the intensive care unit (ICU) to prevent secondary endogenous infections developing in general 'late'; (c) a high standard of hygiene to prevent exogenous infections that may occur throughout the ICU stay; (d) surveillance samples of throat and rectum to distinguish between the three types of infection, to monitor compliance and efficacy of treatment and to detect emergence of resistance at an early stage. The most recent and rigorous meta-analysis examined 33 randomized SDD trials involving 5727 patients. It shows significant reductions, in overall mortality by 20% and in the incidence of lower airway infections by 65%. It failed to detect any report on the emergence of resistance and associated superinfections and/or out-breaks in the 33 studies covering a period of more than 10 years. Using the criterion of cost-per-survivor, four recent randomised trials showed that it is cheaper to produce a survivor using SDD than with the traditional approach.