Fluconazole-resistant Candida parapsilosis complex candidemia and analysis of mutations in the ERG11 gene from Pakistan.

BACKGROUND: Recent reports of the emergence of fluconazole resistance in Candida parapsilosis species complex poses a challenge, more specifically in settings where echinocandin-based treatment regime is not feasible. OBJECTIVE: This study reported emergence of fluconazole resistance in C. parapsilosis species complex strains isolated from blood cultures. MATERIALS AND METHODS: This retrospective observational study was conducted from 2018 to 2020 at a tertiary care laboratory from Pakistan. Fluconazole-resistant C. parapsilosis species complex fungemia cases were identified from laboratory database and clinical details were collected. Identification of C. parapsilosis species complex was done using API 20C AUX and Cornmeal Tween80 agar morphology. Minimum inhibitory concentrations (MICs) were determined using Sensititre YeastONE and interpretation was done with CLSI M60 ED1:2017. ERG11 gene region was amplified and sequenced by Sanger sequencing and analysed by MEGA 11 Software. RESULTS: A total of 13 (8.5%) fluconazole-resistant isolates were identified from 152 C. parapsilosis species complex candidemia cases. Fluconazole MICs of resistant isolates ranged between 8 and 256 µg/mL. Analysis of ERG11 gene revealed nonsynonymous mutations at position Y132F in 86% of the fluconazole-resistant isolates. Diabetes and hospitalization were important risk factors for candidemia with fluconazole-resistant C. parapsilosis complex. CONCLUSION: This is the first report of the emergence and molecular mechanisms of fluconazole resistance in C. parapsilosis species complex from Pakistan. Y132F mutation in the ERG11 gene was the most common mutation in fluconazole-resistant strains. These findings are concerning and necessitate better diagnostics, newer antifungals, ongoing surveillance and further insights on resistance mechanisms in the country.

Breast development and disorders in children and adolescents.

Breast masses are infrequently encountered in pediatric and adolescent populations. Most breast masses in children are benign entities arising from embryological defects which can be managed once breast development is complete. Diagnostic and management dilemmas arise when fibroepithelial lesions of the breast are seen in clinical practice. Differentiation between a fibroadenoma and a phyllodes tumor is important to guide management. Breast cancer in children under 18 years of age is extremely rare and invasive diagnostic testing and aggressive management is only recommended when clinical suspicion of malignancy is very high. Patient and caregiver counseling plays an important role in the management of these diseases. While adult-onset breast diseases have been studied very closely, there is a dearth of literature on pediatric breast anomalies. This review aims to provide a scoping overview of the available literature on benign, fibroepithelial, and malignant lesions of the breast in pediatric and adolescent populations to help guide physicians and surgeons with decision-making regarding the diagnosis and management of pediatric breast diseases.