C. auris is an emerging fungal pathogen with high prevalence of resistance to current antifungal agents. Central nervous system infection with C. auris has been infrequently described. We describe here an adult with nosocomial CSF shunt infection due to multi drug resistant C. auris. Systemic therapy with echinocandin and flucytosine failed. Fortunately, administration of daily intraventricular caspofungin 10 mg for 10 days in conjunction with systemic voriconazole resulted in both clinical and microbiological cure.

Since it has been considered that Candida species in food or drinks may, following ingestion, enter the bloodstream and cause fungaemia, the presence of these yeast species in traditional alcoholic beverages may be of some clinical significance. Thus we attempted to assess virulence factors and antifungal susceptibility profile of Candida strains and other potential pathogenic yeasts isolated from palm wine and sorghum beer (tchapalo). Of the 23 yeast isolates from palm wine, phospholipase, esterase and haemolysin production was revealed amongst 69.6%, 65.2% and 100% isolates respectively with high activity belonging to Candida tropicalis strains. All the isolates were biofilm producers at variable degree but none showed proteinase activity. When the isolates were tested for their susceptibility to five antifungal agents, we found that ketoconazole (91.3%) followed by fluconazole (78.3%) and amphotericin B (73.9%) were the most potent agents. Of the 14 isolates from tchapalo, 57.1%, 87.5% and 57.1% exhibited phospholipase, haemolysin and esterase activity respectively. They did not also show proteinase activity while 87.5% produced biofilm. The majority of the isolates were susceptible to azoles (92.7%) and amphotericin B (85.3%) but they were 5-flucytosine resistant like palm wine strains.

Cryptococcosis is a fungal infection that is typically associated with acquired immunodeficiency syndrome (AIDS). The advent of highly active antiretroviral therapy has decreased the frequency of this infection, but has led to the emergence of atypical cases of immune reconstitution inflammatory syndrome (IRIS). Here, we describe the case of a 40-year-old man who was diagnosed with HIV infection and cryptococcal meningitis. He was successfully treated with antifungals and then started antiretroviral therapy. The patient returned to the hospital 15 months later complaining of fever, pain, and neck swelling. A computed tomography (CT) scan revealed a conglomerate of necrotic lymph nodes in the supraclavicular region. He underwent biopsy and histology showed granulomatous inflammation with fungal elements, consistent with Cryptococcus. He tested positive for serum cryptococcal antigen. The patient was treated with liposomal amphotericin and flucytosine. After induction therapy, he was re-started on fluconazole. The final fungal cultures were negative. We attributed our patient's clinical presentation to "paradoxical" IRIS, which was associated with his previously treated cryptococcosis. Near resolution of the supraclavicular mass was noted at the 3-month follow-up.

FLC family, a conserved fungus-specific family of integral membrane proteins, has been demonstrated to play important roles in flavin transport, growth, and virulence in several fungi but not yet in Cryptococcus neoformans. In this study, we have identified the single homologue of flavin adenine dinucleotide transporter in the opportunistic pathogen C. neoformans. The computational and phylogenetic analysis confirmed the fungal specificity of cryptococcal Flc1 protein, thus providing a promising drug target for clinical treatment of cryptococcosis. Disruption of FLC1 conferred sensitivity to 1% Congo red and 0.02% SDS, as well as leading to impaired chitin distribution in cell wall as observed with Calcofluor White staining, which collectively indicated the roles of FLC1 in maintenance of cell wall integrity. Further investigations revealed the defects of flc1Δ mutant in resistance to poor nutrition and elevated temperatures, and the ability to undergo invasive growth under nutrient-depleted conditions was reduced as well in flc1Δ mutant, suggesting the roles of Flc1 in response to environmental stresses. More importantly, our results showed that flc1Δ mutant exhibited severe susceptibility to antifungal aminoglycosides (hygromycin B and geneticin) and amphotericin B, but developed multidrug resistance to flucytosine and rapamycin, which provided great hints for therapeutic failure of cryptococcosis in clinic with the standard combination therapy. Finally, typical virulence factors including melanin biosynthesis and capsule formation in flc1Δ mutant were reduced as well, indicating the possible involvement of Flc1 in virulence.

Cryptococcal infection has been documented in 2.8% of solid-organ transplant recipients, with the median time to disease onset being 21 months. Renal transplant recipients account for the majority of cases. Most patients present with central nervous system or disseminated disease, with only a minority having cutaneous manifestations. We present the case of a 47-year-old female renal transplant recipient who presented with refractory acute cellulitis 7 months after transplant. She had received thymoglobulin induction and was on a maintenance immunosuppressive regimen of tacrolimus, mycophenolic acid, and prednisone (5 mg/d). She did not respond to broad-spectrum antibacterial therapy for presumed bacterial cellulitis. Skin and soft tissue biopsies subsequently showed the presence of yeast; Cryptococcus neoformans was recovered in culture. Blood cultures, chest radiography, and cerebrospinal fluid sampling were negative, which resulted in a diagnosis of multifocal soft tissue cryptococcosis, a form of disseminated disease. Serum cryptococcal antigen testing was strongly positive (≥ 1:2560). The patient's immunosuppression was reduced, and she received treatment with liposomal amphotericin B and flucytosine for 2 weeks, which resulted in symptomatic improvement. This was followed by 1 year of consolidation and subsequent maintenance therapy with fluconazole. This case should increase awareness of the broader differential diagnosis of soft tissue infection in immunocompromised patients. Her case mimicked bacterial cellulitis, which delayed administration of effective therapy. Although our patient was initially diagnosed via biopsy, early clinical suspicion and serum cryptococcal antigen testing can lead to the correct diagnosis more rapidly. As transplant patients return to their community providers, heightened vigilance for unusual infections and presentations is warranted. The possibility of a cryptococcal cause for acute soft tissue infection should be considered, even in the absence of pulmonary or central nervous system involvement.