In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris.

OBJECTIVE: Candida auris has emerged as a health-care-associated and multidrug-resistant fungal pathogen of great clinical concern. As many as 50% of C. auris clinical isolates are reported to be resistant to amphotericin B, but no mechanisms contributing to this resistance have been identified. Here we describe a clinical case in which high-level amphotericin B resistance was acquired in vivo during therapy and undertake molecular and genetic studies to identify and characterize the genetic determinant of resistance. METHODS: Whole-genome sequencing was performed on four C. auris isolates obtained from a single patient case. Cas9-mediated genetic manipulations were then used to generate mutant strains harbouring mutations of interest, and these strains were subsequently subjected to amphotericin B susceptibility testing and comprehensive sterol profiling. RESULTS: A novel mutation in the C. auris sterol-methyltransferase gene ERG6 was found to be associated with amphotericin B resistance, and this mutation alone conferred a >32-fold increase in amphotericin B resistance. Comprehensive sterol profiling revealed an abrogation of ergosterol biosynthesis and a corresponding accumulation of cholesta-type sterols in isolates and strains harbouring the clinically derived ERG6 mutation. CONCLUSIONS: Together these findings definitively demonstrate mutations in C. auris ERG6 as the first identified mechanism of clinical amphotericin B resistance in C. auris and represent a significant step forward in the understanding of antifungal resistance in this emerging public health threat.

The role of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with mycosis fungoides.

PURPOSE: The aim of the present study is to evaluate the possible role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in the management of mycosis fungoides (MF). MATERIALS AND METHODS: Nineteen patients (mean age, 40.6 years; median age 41 years; 16 males and 3 females) with risk of secondary lymph node (LN) involvement (those with large cell transformation, tumors, erythroderma, or enlarged LNs on physical examination) were included in the study. All patients underwent PET-CT scan by injecting 0.06 mCi/kg of F18 FDG. The maximum standard uptake value (SUVmax) was recorded for each patient. RESULTS: The (18)F-FDG PET-CT was positive in 15 patients. PET-CT detected local cutaneous disease in 13 cases. The range of SUVmax is 2.8-14.1. Out of 19 patients, hypermetabolic adenopathy is found in 9 patients and visceral involvement in one. CONCLUSIONS: Although the study population is small our findings suggests that (18)F-FDG PET-CT can detect cutaneous and extracutaneous lesions in MF and may guide biopsies especially in patients with risk of secondary LN involvement.