Genetically related micafungin-resistant Candida parapsilosis blood isolates harbouring novel mutation R658G in hotspot 1 of Fks1p: a new challenge?

BACKGROUND: Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. OBJECTIVES: To determine the prevalence of echinocandin resistance and the underlying mechanism for a large collection of C. parapsilosis blood isolates and to determine whether the echinocandin-resistant isolates were clonally related. METHODS: C. parapsilosis blood isolates (n = 213) were subjected to antifungal susceptibility testing (CLSI M27), for micafungin, anidulafungin, amphotericin B and, if appropriate, caspofungin. Hotspot (HS) 1 and HS2 of FKS1 were sequenced for all isolates (n = 213) and microsatellite typing was performed for echinocandin-resistant isolates. RESULTS: All isolates were susceptible to amphotericin B and two isolates were intermediate to anidulafungin (MIC = 4 mg/L), while micafungin resistance was noted in four isolates (MIC >8 mg/L); three of which were also fluconazole resistant and therefore were MDR. Interestingly, micafungin-resistant isolates, but not those intermediate to anidulafungin, carried novel mutation R658G in HS1 of Fks1p; three of which also harboured Y132F+K143R in Erg11. The first isolate (MICR1) was recovered in November 2017 from a patient admitted to paediatric gastroenterology who showed therapeutic failure under caspofungin treatment. MICR2-MICR4 were collected during 2018-19 and were recovered from three echinocandin-naive paediatric-surgery patients; the isolates shared the same genotype. CONCLUSIONS: Herein, for the first time (to the best of our knowledge), we identified micafungin-resistant C. parapsilosis blood isolates harbouring a novel mutation in HS1 of FKS1, which was likely attributable to in vitro micafungin resistance and in vivo caspofungin therapeutic failure. The acquisition of micafungin-resistant C. parapsilosis isolates in echinocandin-naive patients likely implicates clonal expansion, as supported by the close genetic relatedness of MICR2-MICR4.

Nutritional Experiences of Parents of Children Who Had Gastric Transposition Surgery.

This study aimed to understand the postoperative nutritional experiences of parents of children who had undergone gastric transposition surgery after corrosive esophageal injury. The study had a descriptive qualitative research design, and used a structured interview form as a result of the COVID-19 pandemic. The population of the study consisted of the parents of 12 children who had undergone gastric transposition surgery at the pediatric surgery clinic of a university hospital in an urban area in Turkey. Thematic analysis was conducted on the transcripts using the MAXQDA program. Four main themes emerged and five supporting sub-themes were identified. The main themes were what we experienced in the postoperative nutrition process, coping with how we live, what we want to know, and our recommendations to healthcare professionals. Family-centered care should be a main focus when caring children who have had gastric transposition surgery, and children and their parents should be supported by a multidisciplinary team.