Variability in antifungal and antiviral use in hospitalized children

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed.Infect Control Hosp Epidemiol2017;38:743–746</jats:p

Antifungal activity of lactic acid bacteria

Enrichment culture techniques produced more than 1200 isolates of lactic acid bacteria (LAB) that were screened for antifungal activity against the indicator mould Aspergillus fumigatus. Approximately 10% of the LAB were active, but only 4% had medium or strong activity in an agar plate assay. The majority of isolates with strong antifungal activity were Lactobacillus coryniformis strains, but Lactobacillus plantarum and Pediococcus pentosaceus were also frequently identified. Some of the isolates lost activity during storage but most maintained their fungal inhibitory effect. Large variations in sensitivity were observed between different moulds and yeasts. Antifungal cyclic dipeptides and phenyllactic acid were detected in culture filtrates from several of the LAB isolates. Lactobacillus coryniformis subsp. coryniformis strain Si3 produced an antifungal compound that lost activity when treated with proteinases. The antifungal peptide(s) was heat stable, with a size of approx. 3kDa and had maximum activity at pH 3.0 to 4.5. Addition of ethanol to the growth medium of strain Si3 prevented a decline in observed antifungal activity during the stationary phase. Glycerol addition to agar plates with L. coryniformis strains, overlaid with soft agar suspensions of yeast cells or fungal spores, strongly enhanced the antifungal effect. This was particularly true with spoilage moulds and yeasts, e.g. Penicillium roqueforti and Pichia anomala, not normally affected by the antifungal metabolites of L. coryniformis. Chemical and genetic data suggested that reuterin (3-hydroxypropionaldehyde) was the cause of this effect. The glycerol/diol dehydratase operon of L. coryniformis was partially elucidated and found to be similar to that Lactobacillus collinoides. Bioassay-guided isolation of new metabolites from LAB revealed that Lactobacillus plantarum MiLAB 14 produces hydroxylated fatty acids with strong antifungal effects. 3-Hydroxydecanoic acid, 3-hydroxydodecanoic acid, 3-hydroxytetradecanoic acid and 3-hydroxy-5-cis-dodecenoic acid were characterized from the supernatant of MiLAB 14. The hydroxy fatty acids had total inhibitory effects in the range 10 to >100 µg ml-1 against several moulds and yeasts

Exploring hidden dimensions of soil fungal biodiversity: A simple technique to detect soil fungi resistant to antifungal compounds

Soils are known to be ultimate and complex reservoirs of microbial diversity. The complex dimensions of bacterial and fungal diversity in tropical soils and microbial community dynamics are underexplored. Isolation techniques aimed at Actinomycetes generally employ highly selective media, powerful antibiotics and antifungal compounds to suppress undesirable bacteria and fungi. However some soil fungi may show their resistance towards these antifungal compounds. During our work to explore soil actinomycetes diversity, slides coated with Arginine Vitamin agar (AVA) incorporating a cocktail of antibiotics and antifungal compounds such as Nystatin, Cycloheximide, Terbinafin, Griseofulvin, and Fluconazole were exposed to soil environment and were retrieved at intervals of 4, 7, 15 and 28 days for detail microscopic studies of surface colonies. Along with actinomycetes the presence of unidentified aseptate and septate fungi was revealed indicating their resistance to combination and concentration of antifungals. Heat treatment of the soil was found to cause considerable decrease in fungal contamination probably due to elimination of heat labile fungi. Our results have led us to develop a simple procedure to sample the interesting and industrially useful strains of soil fungi resistant to common antifungal compounds. Some fungal strains are reported resistant to certain antifungals with resulting therapeutic failures as use of these antifungals inevitably selects resistant fungi, thereby pressing the urge for continuing and cyclical need of new antifungals (Augustin et al., 2004). This technique could prove useful to detect novel antifungal resistant strains with potential to emerge as novel human pathogens. It has not escaped our notice that the probability of such finding could also help to verify whether these fungi could utilize such antifungal compounds through use of hitherto undiscovered metabolic pathways and novel enzymes leading to identification of genes responsible for antifungal resistance

Combined antifungal resistance and biofilm tolerance: the global threat of Candida auris

The enigmatic yeast Candida auris has emerged over the last decade and rapidly penetrated our consciousness. The global threat from this multidrug-resistant yeast has generated a call to arms from within the medical mycology community. Over the past decade, our understanding of how this yeast has spread globally, its clinical importance, and how it tolerates and resists antifungal agents has expanded. This review highlights the clinical importance of antifungal resistance in C. auris and explores our current understanding of the mechanisms associated with azole, polyene, and echinocandin resistance. We also discuss the impact of phenotypic tolerance, with particular emphasis on biofilm-mediated resistance, and present new pipelines of antifungal drugs that promise new hope in the management of C. auris infection

Formulation Of Lengkuas Rhizome (Alpinia Galanga L.) Extract's Gel AS Antifungal With Hidroxy Prophyl Methyl Cellulosae (Hpmc) And Carbopol Base

Infection of Malassezia furfur on skin can be caused by bad factor. One of the materials that can be used as an antifungal is Lengkuas rhizome extract (Alpinia galanga L.). This study had purpose to determine the antifungal activity and the effectiveness of gels Lengkuas rhizome extract on pathogenic fungi using maseration method with etanol 96%. Gel making is used HPMC and carbopol base. Testing activity of extract and testing the effectiveness of the gel by disc diffusion method (Kirby-Bauer test). Screening result showed that the extract contains triterpenoids, flavonoids and essential oil. Based on the test results against Malassezia furfur, antifungal activity of the extract in the gel increased compared to extracts without formulated into a gel. But the activity increasing was not significant based on statistical analysis with one-way ANOVA test obtained a significance of 0.234 (p> 0.05)

Global Antifungal Profile Optimization of Chlorophenyl Derivatives against Botrytis cinerea and Colletotrichum gloeosporioides

Twenty-two aromatic derivatives bearing a chlorine atom and a different chain in the para or meta position were prepared and evaluated for their in vitro antifungal activity against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. The results showed that maximum inhibition of the growth of these fungi was exhibited for enantiomers S and R of 1-(40-chlorophenyl)- 2-phenylethanol (3 and 4). Furthermore, their antifungal activity showed a clear structure-activity relationship (SAR) trend confirming the importance of the benzyl hydroxyl group in the inhibitory mechanism of the compounds studied. Additionally, a multiobjective optimization study of the global antifungal profile of chlorophenyl derivatives was conducted in order to establish a rational strategy for the filtering of new fungicide candidates from combinatorial libraries. The MOOPDESIRE methodology was used for this purpose providing reliable ranking models that can be used later

Isolation, characterization and selection of bacterial isolates from a suppressive soil with beneficial traits to plants

Backgrounds This study focused on the characterization and selection of bacterial strains obtained from a suppressive soil displaying antifungal activity against the soilborne phytopathogenic fungi Rosellinia necatrix. Bacterial profile from this suppressive soil were first obtained by 16S rRNA gene sequencing, revealing a significant increase in the bacterial class Gammaproteobacteria, especially in some antagonistic representatives of Pseudomonas spp. Objectives To obtain and characterize a collection of 246 bacterial isolates obtained from this suppressive soil, in order to identify new strains with antifungal activity against fungal phytopathogens. Methods To obtain the bacterial collection, we performed an isolation on a selective medium for Pseudomonas-like microorganisms. Further characterization tests were used in order to analyse the bacterial collection, including identification of the general metabolic profile of glucose, the profiling of antifungals produced, including both the putative production of antifungal compounds and lytic exoenzymes, and the evaluation of traits related with beneficial effects on plants. Conclusions A final selection of representative strains resulted in antifungal isolates belonging to the genus Pseudomonas, but also some representatives of the genera Serratia and Stenotrophomonas. These selected strains were tested for plant protection by an in vivo experiment using avocado and wheat plants challenged by the pathogen R. necatrix, showing all of them an antifungal ability and plant disease protection. Pseudomonas-like strains isolated from suppressive soils constitute an excellent source for novel microbial biocontrol agents against soilborne fungal pathogens. This work was supported by grant AGL2014-52518-C2-1-R. Carmen Vida and Sandra Tienda are supported by a PhD fellowship from the FPI program of the Spanish Government.This work was supported by grant AGL2014-52518-C2-1-R. Carmen Vida and Sandra Tienda are supported by a PhD fellowship from the FPI program of the Spanish Government; Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in promising strategies to enhance or restore critical immune functions in allogeneic HSCT recipients. Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. This review summarizes and critically discusses the available data of immunotherapeutic strategies in allogeneic HSCT recipients suffering from invasive fungal infection