Antifungal Type Research Articles

Epidemiology and Outcome of Candidemia in ICU, Mashhad, a 6-Year Multi-Center Study

Background and aim: candidemia is a state that usually happens in immunocompromised patients. Thus it is more prevalent in ICU patients. This status brings mortality and morbidity; however, the outcome is various in different ICU care settings. The aim of this study is to assess epidemiology of outcome of candidemia in ICU in Mashhad during a 6-year period. Method: in a cross-sectional study between 2012 and 2018 in different ICU centers affiliating with Mashhad University of Medical Sciences, data of candidemia patients were extracted from hospital information system. These data were demographic, past medical history, result of the culture, and antifungal treatment. Result: totally, 55 patients (22 men and 33 women) were included in the study. The mean age of the patients was 45.9±1.9 years. Furthermore, the mean duration of hospitalization and the mean duration of ICU care were 43 and 37 days, respectively. Five patients had a history of immunosuppressive treatment and four patients were prescribed antifungal treatment in their past medical history (all with fluconazole and none with Itraconazole). Eighteen patients received caspofungin, eleven Amphotericin B treatment, and two fluconazole with no significant difference in outcome of the patients regarding antifungal type. In case of coincident antibiotic treatment, Carbapenems were prescribed in 43 patients, Glycopeptides in 48 patients, 25 patients had Cephalosporin treatment, and 13 patients had Fluoroquinolone treatment with no significant difference regarding the antibiotic type. Conclusion: The mortality percent of candidemia in ICU was 69.1 within mean time of 37 days. Furthermore, there was no significant difference in outcome of the patients regarding using Caspofungin or Amphotericin. Timely initiation of antifungal regarding to the culture result may bring better outcomes.

Development of a Novel Evaluation System of Tip Growth for Antifungal Compounds with the Use of Candida Albicans

Mycosis is an infection to human caused by fungi, such as mold and yeast. Among mycosis, deep mycosis which infects organs and tissues, has become a particularly serious problem. To treat those deep mycosis, chemotherapy with antifungal agents is used. However, the types of antifungals are few and the treatment options are limited. Since fungi and humans have similar cell structures, existing antifungal agents have also been reported to have side effects on humans. Furthermore, the emergence of resistant fungi has become a problem due to the long-term use of the drug.From those problems, development of an antifungal agent having a new mechanism of action is required. Therefore, our laboratory focused on tip growth, a growth method specific to fungi. Tip growth elongates the cell by repeating the decomposition and synthesis of the cell wall (β-1,3-D-Glucan). It has been reported that the cell wall-degrading enzyme β-1,3-D-Glucanase (BGL2) involved in this tip growth is vesicular transported from the inside of the cell to the growth point. We consider that targeting vesicle transport during tip growth will provide selective toxicity to fungi. The purpose of this study is to develop novel antifungal agents targeting vesicle transport during fungal tip growth. An evaluation system for visualizing vesicle transport was constructed by fusing green fluorescent protein GFP downstream of BGL2 to be transported to the growth point by expression of the protein in Saccharomyces cerevisiae (the results of the localization were shown in Fig.1).Using this evaluation system, vesicle transport inhibitory activity was screened for 100 kind herbal medicine extract. As a result, vesicle transport inhibitory activity was observed in 8 types.In addition, we attempted to construct a similar evaluation system using Candida albicans and aimed to evaluate fungi that form hyphae that cause actual mycosis.Fig.1 Confocal laser scanning microscope image of an evaluation system for antifungal compounds using S. cerevisiae.(a) Localization of BGL2-EmGFP to growth point.(b) Localization of BGL2-EmGFP to the division site.(C) Intracellular distribution of BGL2-EmGFP treated with vesicle transport inhibitor. Figure 1

The antifungal pipeline: the need is established. Are there new compounds?

Our review summarizes and compares the temporal development (eras) of antifungal drug discovery as well as antibacterial ventures. The innovation gap that occurred in antibacterial discovery from 1960 to 2000 was likely due to tailoring of existing compounds to have better activity than predecessors. Antifungal discovery also faced innovation gaps. The semi-synthetic antibiotic era was followed closely by the resistance era and the heightened need for new compounds and targets. With the immense contribution of comparative genomics, antifungal targets became part of the discovery focus. These targets by definition are absolutely required to be fungal- or even lineage (clade) specific. Importantly, targets need to be essential for growth and/or have important roles in disease and pathogenesis. Two types of antifungals are discussed that are mostly in the FDA phase I-III clinical trials. New antifungals are either modified to increase bioavailability and stability for instance, or are new compounds that inhibit new targets. One of the important developments in incentivizing new antifungal discovery has been the prolific number of publications of global and country-specific incidence. International efforts that champion global antimicrobial drug discovery are discussed. Still, interventions are needed. The current pipeline of antifungals and alternatives to antifungals are discussed including vaccines.

The Effectiveness of Antifungal Controlling Aspergillus Niger Growth on Plasterboard

Good indoor environmental quality is desired for a healthy indoor environment. The microbial growth under indoor environments contribute to the poor indoor environmental quality that can cause various of health problems. In this study, the applications of three types of antifungals to prevent microbial migration, subsequent growth and bio-deterioration of the substrates. The aim of this research was to evaluate the coating-bio resistance in remediation of indoor fungal using three types of antifungals with different types of wall finishing materials. The treatment was exposed to optimum temperature and relative humidity at 30°C and 90% respectively. The potassium sorbate, zinc salicylate and calcium benzoate are tested against Aspergillus niger which is collected from indoor rooms. This study has revealed the growth of A. niger are more affected by the potassium sorbate on thick wallpaper, which is the percentage growth are 47%.

Antifungal type 1 responses are upregulated in IL-10-deficient mice

C57BL/6 mice are highly resistant to infections caused by Candida albicans and Aspergillus fumigatus. To elucidate the role of IL-10 produced by C57BL/6 mice during these infections, parameters of infection and immunity to it were evaluated in IL-10-deficient and wild-type mice with disseminated or gastrointestinal candidiasis or invasive pulmonary aspergillosis. Unlike parasitic protozoan infection, C. albicans or A. fumigatus infection did not induce significant acute toxicity in IL-10-deficient mice, who, instead, showed reduced fungal burden and fungal-associated inflammatory responses. The increased resistance to infections as compared to wild-type mice was associated with upregulation of innate and acquired antifungal Th1 responses, such as a dramatically higher production of IL-12, nitric oxide (NO) and TNF-α as well as IFN-γ by CD4 + T cells. Pharmacological inhibition of NO production greatly reduced resistance to gastrointestinal candidiasis, thus pointing to the importance of IL-10-dependent NO regulation at mucosal sites in fungal infections. These results are reminiscent of those obtained in genetically susceptible mice, in which IL-10 administration increased, and IL-10 neutralization decreased, susceptibility to C. albicans and A. fumigatus infections. Collectively, these observations indicate that the absence of IL-10 augments innate and acquired antifungal immunity by upregulating type 1 cytokine responses. The resulting protective Th1 responses lead to a prompt reduction of fungal growth, thus preventing tissue destruction and lethal levels of proinflammatory cytokines.

Phenotype and genotype of Candida albicans strains isolated from pregnant women with recurrent vaginitis.

Fourteen out of 80 pregnant women receiving prenatal care presented signs and symptoms of recurrent vaginal candidiasis. Candida albicans strains were isolated from 12 patients (85.7%), and these were submitted to morphotyping (morphological characteristics of the colony), antifungal typing (pattern of sensitivity to amphotericin B, 5-fluorcytosine, myconazole, ketoconazole and fluconazole) and genotyping (electrophoretic migration of DNA fragments digested with EcoRI and HinfI). Alteration of morphotype and antifungal type was observed in 50% of the patients, but the genotype of the strains isolated from the same patients at different times was identical in all subjects. The predominant morphotypes presented continuous fringes and the basic changes observed among antifungal types was the emergence of strains resistant to myconazole, which was the drug used for the treatment of the first episode of vaginitis. We conclude that recurrent vaginal candidasis is caused by the persistence of a single yeast genotype that undergoes morphological and behavioral changes in the presence of antifungal agents due to the selective pressure to which it is submitted.