The significant increase in the use of antifungal agents, both for the treatment of candidiasis and invasive aspergillosis and as azole fungicides in agricultural crop protection has resulted in the emergence of resistant clinical isolates, particularly to triazoles and echinocandins. Notably, among isolates that were primarily sensitive to fluconazole such as Candida parapsilosis and Candida tropicalis have witnessed an emerging resistance development. Also for echinocandins, the occurrence of Candida isolates with lower susceptibility to these drugs has been reported, which is possibly due to its broad clinical use. Triazole resistance among Aspergillus fumigatus and other Aspergillus species is commonly found in European and Asian countries. Specific mutations are associated with azole resistance in A. fumigatus and these mutations are now reported globally from six continents. Therefore, we highlight the need to conduct antifungal resistance surveillance studies using clinical isolates of Candida and Aspergillus in different geographical regions and monitoring of the infection rates in distinct population groups for early detection of resistance to these drugs and implementation of efficient policies for infection control and treatment.

f Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 g/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis.

BackgroundCandidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil.MethodsThis was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection.ResultsWe identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %.ConclusionsThe clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

Background:We identified auranofin as an antimicrobial compound utilizing a highthroughput screen using a Caenorhabditis elegans-Staphylococcus aureus infection model. Results/methodology: Treatment of infected nematodes with auranofin resulted in a prolonged survival rate of 95%, reached with 0.78 μg/ml. Further investigation of the antimicrobial activity of auranofin found inhibition against S. aureus, Enterococcus faecium and Enterococcus faecalis. Importantly, the fungal pathogens Cryptococcus neoformans was also effectively inhibited with an MIC at 0.5 μg/ml. Auranofin appears to target the thioredoxin system. Conclusion: This work provides extensive additional data on the antibacterial effects of auranofin that includes both reference and clinical isolates and reports a novel inhibition of fungal pathogens by this compound.

We identified a case of breakthrough candidemia in a 25-year-old patient receiving micafungin prophylaxis (50 mg/day). Five Candida glabrata isolates were obtained from blood cultures and were classified as multidrug-resistant isolates, since all of them exhibited high MICs for echinocandin and azole drugs. A mutation (S663F) in hot spot 1 of the FKS2 gene was found in all five isolates. This mutation yielded a 1,3-␤-D-glucan synthase enzyme with highly reduced sensitivities to echinocandin drugs.

Cardiovascular diseases are the most common cause of mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases; thus, anti-inflammatory and antioxidant agents that modulate redox balance have become research targets so as to evaluate their molecular mechanisms of action and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant properties due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also has prominent anti-inflammatory activity, possibly interrelated with its antioxidant effect, and is also involved in the modulation of lipid and glucose metabolism. Considering the potential beneficial effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, the aim of the present review was to describe the molecular and cellular mechanisms associated with the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, particularly atherosclerosis. The beneficial properties and safety profile of astaxanthin indicate that this compound may be used for preventing progression or as an adjuvant in the treatment of cardiovascular diseases.

The epidemiology of candidemia varies geographically, and there is still scarce data on the epidemiology of candidemia in Latin America (LA). After extensive revision of medical literature, we found reliable and robust information on the microbiological aspects of candidemia in patients from 11 out of 21 medical centers from LA countries and 1 out of 20 from Caribbean countries/territories. Based on 40 papers attending our search strategy, we noted that C. albicans remains the most common species causing candidemia in our region, followed by C. parapsilosis and C. tropicalis. In Argentina, Brazil, and Colombia, a trend towards an increase in frequency of C. glabrata candidemia was observed. Although resistance rates to fluconazole is under 3%, there was a slight increase in the resistance rates to C. albicans, C. parapsilosis and C. tropicalis isolates. Echinocandin resistance has been reported in a few surveys, but no single study confirmed the resistant phenotype reported by using molecular methods. We highlight the importance of conducting continuous surveillance studies to identify new trends in terms of species distribution of Candida and antifungal resistance related to episodes of candidemia in LA. This information is critical for helping clinicians to prevent and control Candida bloodstream infections in their medical centers.