BackgroundThe purpose of this study was to unveil whether azole antifungals used in agriculture, similar to the clinical azoles used in humans, can evoke resistance among relevant human pathogens like Aspergillus fumigatus, an ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles was investigated. Antifungal susceptibility testing of environmental and clinical isolates of A. fumigatus was performed according to the CLSI M38-A2 protocol. In vitro induction assays were conducted involving daily incubation of susceptible A. fumigatus isolates, at 35°C and 180 rpm, in fresh GYEP broth medium supplemented with Prochloraz (PCZ), a potent agricultural antifungal, for a period of 30 days. Minimal inhibitory concentrations (MIC) of PCZ and clinical azoles were monitored every ten days. In order to assess the stability of the developed MIC, the strains were afterwards sub-cultured for an additional 30 days in the absence of antifungal. Along the in vitro induction process, microscopic and macroscopic cultural observations were registered.ResultsMIC of PCZ increased 256 times after the initial exposure; cross-resistance to all tested clinical azoles was observed. The new MIC value of agricultural and of clinical azoles maintained stable in the absence of the selective PCZ pressure. PCZ exposure was also associated to morphological colony changes: macroscopically the colonies became mostly white, losing the typical pigmentation; microscopic examination revealed the absence of conidiation.ConclusionsPCZ exposure induced Aspergillus fumigatus morphological changes and an evident increase of MIC value to PCZ as well as the development of cross-resistance with posaconazole, itraconazole and voriconazole.

No abstract

No abstract

Acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. The main goal of this study was to assess the development of cross‐resistance between agricultural and clinical azoles by Candida spp. An in vitro induction assay was performed, for a period of 90 days, with prochloraz (PCZ) – an agricultural antifungal. Afterward, the induced molecular resistance mechanisms were unveiled. MIC value of PCZ increased significantly in all Candida spp. isolates. However, only C. glabrata developed cross‐resistance to fluconazole and posaconazole. The increased MIC values were stable. Candida glabrata azole resistance acquisition triggered by PCZ exposure involved the upregulation of the ATP binding cassette multidrug transporter genes and the transcription factor, PDR1. Single mutation previously implicated in azole resistance was found in PDR1 while ERG11 showed several synonymous single nucleotide polymorphisms. These results might explain why C. glabrata is so commonly less susceptible to clinical azoles, suggesting that its exposure to agricultural azole antifungals may be associated to the emergence of cross‐resistance. Such studies forward potential explanations for the worldwide increasing clinical prevalence of C. glabrata and the associated worse prognosis of an infection by this species.

Background: Adherence to therapy in bronchial asthma is essential for the control of the disease. Several studies show that non -adherence seems to be the result of different factors and barriers associated with the patient, but also with the prescriber. The most important are the psychological, economic and social aspects. In clinical practice, there are few resources that allow the physician to objectify the degree of compliance of his prescription. The aim of this study was to analyze the degree of adherence to therapy in asthmatic patients followed in a Hospital Immunoallergology Department. Methods:The clinical trials of 63 asthmatic patients followed at the Immunoallergology Department from January to December of 2016 (T0) and from January to December of 2017 (T1) were retrospectively studied. The number of packs prescribed to the patients by the attending physician and the number of packs actually purchased in pharmacies were analyzed in T0 and T1 by means of Electronic Medicines Prescriptions (PEM) records for the following drugs: bronchodilators (BD), inhaled corticosteroids isolated or in combination with bronchodilators (OUT), oral antihistamines (AH), leukotriene antagonists (LCRA), nasal corticosteroids (CN) and oral corticosteroids (CO). The following demographic and clinical variables were analyzed: age, sex, clinical diagnosis, atopy, allergen sensitization and specific immunotherapy treatment (ITE). Results:We found a compliance of 64.76% to the prescription. The drugs which the patients most adhere were oral corticosteroids (73%), followed by leukotriene antagonists and antihistamines (70%). When analysing associations between variables, it was observed that patients who were not under ITE had greater adhesion to the inhalers (BD and CI) (p <0.05). The asthmatic group had a positive association with adherence to the LCRA (p <0.05) and in the analysis by age, we found that the infant population had a positive association with adherence to AH (p <0.05). Conclusions: To improve adherence to therapy in asthma, it is important to address and know patient's compliance. The study of each patient's adherence based on computerized drug prescription and retrieval systems in pharmacies allows prescribing physicians to introduce this variable into the analysis of asthma control.