Prevention Of Fungal Infections Research Articles

Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole.

Voriconazole is the cornerstone of the treatment and prevention of fungal infections. While there is a good correlation between CYP2C19 genotype and voriconazole exposure during prophylactic treatment, no correlation was found in patients with invasive aspergillosis. Proinflammatory cytokines result in inhibition of CYP2C19 enzyme activity (and may result in phenoconversion). Here we investigated the relationship between inflammation, CYP2C19 genotype-predicted-phenotype, and CYP2C19 activity in patients receiving voriconazole. Data were obtained from two prospective studies investigating voriconazole treatment (NCT02074462 and NCT00893555). Dose-corrected voriconazole plasma concentration and C-reactive protein (CRP) were used as proxies for CYP2C19 activity and inflammation, respectively. After data extraction and synthesis, data from 39 patients with paired voriconazole and CRP measurements were available. The distribution of CYP2C19 genotype-predicted metabolizer phenotypes was 31% intermediate (IM), 41% normal (NM), and 28% rapid metabolizer (RM). During inflammation, dose-corrected voriconazole levels were increased by 245%, 278%, and 486% for CYP2C19 NMs IMs and RMs, respectively. Patients with moderate or high CRP levels (>50 mg/L) were phenoconverted to a lower metabolizer phenotype irrespective of their CYP2C19 genotype. In a subgroup analysis of eight patients with longitudinal data available with and without inflammation, the pattern of the dose-corrected voriconazole and CRP measurements were similar, with CYP2C19 activity following decreasing or increasing CRP levels. In conclusion, voriconazole plasma concentrations increase during inflammation due to downregulation of CYP2C19 activity. While this effect appears largest for CYP2C19 RMs, no clinically relevant differences were observed between the CYP2C19 genotypes.

NEW STRATEGIES IN COMBATING FUNGAL PATHOGENS

Background. The relevance of the research is driven by the emerging trend of increasing resistance to existing drugs for the treatment of fungal infections. Addressing this issue is only possible by developing new formulations of antifungal agents or improving existing ones; studying the mechanisms of interaction of drugs with fungal cell walls and their exopolysaccharide matrices; refining delivery methods of antifungal agents, such as DectiSomes, for maximum effectiveness and minimizing side effects; expanding understanding of the immune response mechanisms to fungal infections and developing vaccines for the prevention of these diseases. The research aims to improve methods of diagnosis, treatment, and prevention of fungal infections to enhance the quality of life for patients and reduce the overall impact of these diseases on public health. Aim: To evaluate new treatment strategies for fungal infections to increase the effectiveness of antifungal agents, reduce their toxicity, and slow down the development of resistance. Materials and Methods: The materials for this study included publications of results from contemporary scientific research on the topic. The methods used for conducting the research were: a systematic approach and analysis, literary and critical analysis. Results. Prove the prospects for developing new strategies and techniques for antifungal therapy. By analyzing the results of clinical studies, including the assessment of the effectiveness of various antifungal drugs, it is possible to determine which ones are most effective under certain conditions and for specific types of fungal infections. New methodologies based on the principle of delivering or acting directly on the target area allow reducing the overall burden on the body. Better penetration of drugs into the skin and tissues allows for better control of fungal infection and accelerated healing process. Evaluating side reactions and patient tolerance levels to different drugs helps select antifungal agents that are the safest and most comfortable to use. Conclusion. Fungal infections continue to be a serious public health problem, and the development of new treatment and prevention methods is extremely important. Overall, research in these areas can help develop new therapeutic strategies that are more effective and safer for treating fungal infections, which pose a threat to humanity.

Fungus Infections in Fish

Many factors such as bacteria, viruses, parasites and fungi can cause infections in fish. Fungal infections are often overlooked because they are secondary to other infections. However, these infections can cause serious economic losses as they cause problems such as mortality, growth retardation, deformed appearance due to lesions on the skin, and negatively affect hatching rates, especially in farmed fish. In addition, it can cause infections in aquarium fish and the same findings can be seen in them. This article reviews the classification, aetiology, epidemiology, clinical and pathological findings, possible diagnosis, treatment and prevention of fungal infections in fish.

AmBisome® Formulations for Pediatrics: Stability, Cytotoxicity, and Cost-Effectiveness Studies.

Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be challenging due to the spontaneous tendency of amphotericin B to form aggregates with different biological activity. In this study, the colloidal stability of the liposomes and the chemical stability of amphotericin B were investigated over time at storage conditions. Three liposomal formulations of amphotericin B at 4.0 mg/mL, 2.0 mg/mL, and 0.2 mg/mL were prepared and assayed for changes regarding the dimensional distribution, zeta potential, drug aggregation state, and onset of by-products. Our analyses highlighted that the most diluted formulation, kept at room temperature, showed the greatest changes in the aggregation state of the drug and accordingly the highest cytotoxicity. These findings are clinically relevant since the lower dosages are addressed to the more vulnerable patients. Therefore, the centralization of the dilution of AmBisome® at the pharmacy is of fundamental importance for assuring patient safety, and at the same time for reducing medication waste, as we demonstrated using the cost-saving analysis of drug expense per therapy carried out at the G. Gaslini children hospital.

DEFB114 protein enhances host resistance to fungal infection through the NOD1/2-ATG16L1-NF-κB signaling pathway

The overuse of antibiotics has led to the enhanced resistance of many pathogenic bacteria, posing a threat to human health. Therefore, there is a need to develop green and safe alternatives to antibiotics. Beta-defensins play a crucial role in host defense against pathogens and have multifunctional properties, exerting key roles in innate and adaptive immunity, as well as non-immune processes. In this study, a 210 bp long cDNA sequence of yak DEFB114 gene was amplified and successfully expressed in a prokaryotic system. The DEFB114 protein exhibited significant inhibitory effects on the growth of Aspergillus fumigatus in vitro. When co-cultured with yak macrophages, DEFB114 protein enhanced macrophage phagocytic activity and increased nucleic acid fluorescence intensity (P < 0.05). DEFB114 protein also enhanced the activity of yak macrophages stimulated by inactivated Aspergillus fumigatus spores, increased the release of nitric oxide (NO), and promoted the expression of genes such as γ-actin, Lgals, Man2b, and Capg (P < 0.05). In mice experiments, DEFB114 protein promoted resistance against Aspergillus fumigatus infection, by regulating the NOD1/2-ATG16L1-NF-κB pathway to modulate the host immune response and exert its anti-infective effects. In summary, the yak DEFB114 protein could inhibit the growth of Aspergillus fumigatus and enhance the animal's resistance to pathogenic microorganisms, thereby having significant implications in the treatment and prevention of fungal infections.

Synthesis and study of the antifungal activity of 1-(2-cyanophenyl)-3-heterylureas

In the treatment and prevention of fungal infections of plants, along with fungicides, inducers of systemic plant resistance, also called elicitors, have become particularly important in recent years. In this work, a method was developed for the synthesis of new 3,4-dichloroisothiazol-5-yl and 4-methyl-1,2,3-thiadiazol-5-yl ureas 1,2, containing a 2-cyanophenyl substituent, structurally similar to a known synthetic elicitors isotianil and tiadinil. The protective properties of the obtained compounds on cucumber and pepper leaves infected with B. cinerea, as well as their fungicidal properties against B. cinerea, were studied. It has been established that disubstituted ureas 1,2 exhibit very low fungicidal activity against this fungus, about 11%. At the same time, study on plant leaves showed that compound 2 effectively inhibited the development of gray mold on both cucumber and pepper leaves with an inhibition rate of more than 90%, which was similar to tiadinil. Compound 1 was effective only on cucumber leaves (96.50±0.01%). Isotianil in the experiment showed an average degree of protection – 62.48±1.04% on cucumber leaves and 56.50±1.29% on pepper leaves.

The Therapeutic Efficacy and Blood Drug Concentration of Posaconazole Enteric-Coated Tablets in Preventing Pulmonary Invasive Fungal Disease after HSCT

Introduction The risk of fungal infection in patients after HSCT is high. Prophylactic use of antifungal drugs can significantly reduce the occurrence of invasive fungal disease (IFD) and potential IFD-related mortality. Posaconazole oral suspension shows good preventive effects for patients with neutropenia and severe GVHD . However, there is still a lack of prospective research confirming the effectiveness of posaconazole enteric-coated tablets in preventing fungal infections in HSCT patients. Methods This study is a prospective, non-randomized, single-arm study. 143 patients who received hematopoietic stem cell transplantation at the Transplantation Center of Blood Diseases Hospital, the Chinese Academy of Medical Sciences from December, 2020 to May, 2022 were included. Posaconazole enteric-coated tablets were administered orally at a dose of 300mg QD (double dose for the first day) for the prevention of pulmonary invasive fungal disease from the first day to the 90th day after transplantation. The study collected baseline data, serum posaconazole concentrations, UGT1A4*3 genotype of the involved patients and observed whether pulmonary invasive fungal disease occurred. Retrospective data on the use of other antifungal drugs for the prevention of pulmonary invasive fungal disease at the center were collected as a control group for comparison. After applying propensity score matching at a ratio of 1:2, a comparative analysis was conducted on 140 cases in the posaconazole enteric-coated tablets group and 280 cases in the non-posaconazole group. Results Among the 143 patients who were included in the clinical trial and treated with posaconazole enteric-coated tablets alone for the prevention of fungal infection from day 1 to day 90 after hematopoietic stem cell transplantation, 4 cases developed invasive pulmonary fungal infection, including 1 case of mold and 3 cases of undefined pathogens, with a breakthrough rate of 2.80%, significantly lower than the historical control group breakthrough rate of 7.86% in the non-posaconazole group (P=0.014). In the 90 days after transplantation, a total of 246 measurements of posaconazole blood concentration were performed in the 143 patients in the clinical trial group. The average blood drug concentrations on the 4th, 8th, 15th, 22nd, and 30th day were 930.97 ng/ml, 1143.97 ng/ml, 1569.8 ng/ml, 1652.57 ng/ml, and 1644.75 ng/ml respectively. The blood drug concentration of posaconazole enteric-coated tablets tended to stabilize since the 15th day after treatment. In the 37 patients who tested the UGT1A4*3 genotype, there was no significant correlation between UGT1A4*3 gene polymorphism and posaconazole blood drug concentration. In terms of adverse reactions, the incidence of liver adverse events in this clinical study was 1.4%. Except for a slight increase in ALT after the 14-day medication (18.29 U/L vs. 26.22 U/L, P&amp;lt;0.001), there were no differences in other liver and kidney function laboratory test before and after treatment. Conclusion Posaconazole enteric-coated tablets is a highly safe prophylactic drug for invasive pulmonary fungal infections after HSCT, and its efficacy is superior to other antifungal prophylaxis regimens. Posaconazole enteric-coated tablet blood drug concentration in transplant patients gradually rose over time and tended to stabilize after 15 days of medication. The UGT1A4*3 gene polymorphism has no effect on the blood drug concentration of posaconazole enteric-coated tablets. Keywords Posaconazole enteric-coated tablets, hematopoietic stem cell transplantation, pulmonary invasive fungal disease

To Study The Antifungal Susceptibility Pattern, Molecular Profiling And Its Sequencing Analysis Of Trichophyton Rubrum Isolated From Human Sample: A Cross Sectional Case Study From Uttar Pradesh, India

Introduction: There has been a sudden, unexplained surge in dermatophytoses in India since past 5 years. T. rubrum being the most common etiological agent isolated from clinically diagnosed lesions of cutaneus dermatophytosis. It has a significantly higher capacity of transmission than other anthropophilic dermatophytes. Aim and Objective: To study the Antifungal Susceptibility Pattern , Molecular Profiling and its Sequencing Analysis of Trichophyton rubrum isolated from human Sample. Material and Methods: This was a a prospective study carried out in the Department of Microbiology at Rama Medical College Hospital and Research Centre Mandhana, Kanpur for a period of 1 year i.e, March 2017 to March 2018. A total of 375 clinically suspected cases of superficial fungal infection were collected with proper informed consent. Dermatophytosis was confirmed in cases by direct microscopy and culture methods. Antifungal drug susceptibility profiles, MIC of isolates were 50 90 determined using the broth microdilution method according to the CLSI guidelines. The DNA isolation was done using the Qiagen DNA extraction kit followed by the PCR. The sequencing methods were used for the genetic analysis of virulence gene for the confirmation. Results: Out of the total of 375 clinically suspected cases of superficial fungal infection 31 isolates of Trichophyton rubrum were studied. The ratio of Male were more 27 (87%) as compared to the Female 4 (12.9% ). The maximum number of isolates was found in the Skin 28 (90.3%) followed by the Nail 3 (9.6%). The ITZ was most sensitive toward T. rubrum than KTZ, TBF, and FCZ. The molecular characterization for the detection of 18s gene was performed which was confirmed by the Sequencing Analysis. Conclusion: Antifungal resistance against T. rubrum is increasing over the last few decades due to genetic diversity in the fungal genome. The molecular identification is a gold standard technique for the identification of T. rubrum allowing important factor in providing fungal infection prevention and treatment approaches.

Grapeseed Extract and its Role in Maintaining Oral Health: A Literature Review

Plant products are becoming the topic for discussion because of its properties and many medicinal benefits. Among these natural products, Grapeseed Extract (GSE) is becoming an essential part of medicine. Antibacterial, antioxidants, anti-inflammatory and antiviral are some of the important properties. Due to its antibacterial property it is used to control various bacterial diseases and eased the course of treatment, many oral bacteria are also inhibited by GSE. GSE has shown considerable results in patients with periodontal diseases and treatment of bone loss. GSE is a potent antioxidant and reduces free radicles and oxidative stress thus inhibiting various adverse effects. GSE contains antioxidant properties which protects body from premature ageing. Antifungal properties are very useful in treatment and prevention of fungal infection. Grapeseed is useful in treating oral candidiasis as well. A number of phytochemicals including resveratrol, Proanthocyanidin (PA) are beneficial in treating cancer and prevents recurrence. The protective properties of plant extracts and phytochemicals are recently been used in prevention of most common oral disease like dental caries in children and adults. Many studies are going on about remineralisation efficiency of phytochemicals in the field of dentistry. It has been shown to increase the dentine resin bond strength if it is added in the primer and also effectively reduces the polymerisation. Another important consideration is the safety doses of GSE, it refers to the quantity or percentage in which it is added in the concerned products so it is safely tolerated and its effects are maximum. Overall, GSE contains many useful properties and is of great clinical importance.

Prevalence of Mycoses and Investigation of Fungal Indoor Environment

Background and Aims: The incidence of fungal infections in Saudi Arabia is increasing with an increase in the population of high-risk patients. Still, studies highlighting the impact of environmental fungal agents on infections in Saudi are limited, and none have examined the Medina region despite the city’s stature, diversity, and travel flow. This study aims to determine the fungal distribution across the Medina region. Methods: A randomized 212 indoor samples were collected based on analyzed data from 1374 questionnaires. The prevalence of participants to fungal infection was 19.2% and 26.3% in the risk group. Fungal species were identified via macroscopic and microscopic examination. Results: Two hundred and three (96%) samples showed fungal growth. Yeast identified were 78 (34%) Candida species, 56 (25%) non-Candida species. The study identified 13 genera and 20 species for mould, including 38 (17%) Aspergillus spp., 20 (9%) Rhizopus spp. 9(4%) holoarthic/enteroatric conidiogenesis, 7 (3%) Mucor spp. 4 (2%) of both Penicillium spp. and Neurspora spp. and only 2(1%) of Madurella spp., 3(1%) Epidermophyton spp., 2 (1%) Lichtheimia spp., and 1(1%) Peacilomyces spp. Conclusions: This study identified Aspergillus spp. as the most frequent fungi across the Medina region. The characterization of indoor fungal environment enables healthcare practitioners to anticipate fungal infection for individuals at risk. These findings can aid the prediction and prevention of fungal infections and fungal sensitization among the high-risk populations.

Determination of Usage Doses of Some Chemical Substances in the Prevention of Fungal Infections in Rainbow Trout Eggs

Bu çalışmada, döllenmiş gökkuşağı alabalığı (Oncorhynchus mykiss) yumurtalarında görülen mantar etkenlerine karşı koruyucu tedbirlerin alınması amaçlanmıştır. Döllenmiş yumurtalarda mantar oluşumunu önlemek için farklı dozlardaki formaldehit (0,5, 1 ve 2 ml/l), iyot (0,5, 1 ve 2 ml/l), hidrojen peroksit (5, 10 ve 15 ml/l), elma sirke (1, 5 ve 10 ml/l) ve kaya tuzu (5, 10 ve 15 gr/l) 10'ar dakika süreyle günde bir kez kullanılmıştır. Bu kimyasal maddelerin farklı konsantrasyonlarındaki deneme sonuçları karşılaştırıldığında en iyi yaşama oranının 2 ml/l dozunda iyot uygulanan grupta olduğu tespit edilmiştir. Çalışma sonunda I. denemenin kontrol gurubundaki yumurtaların tamamının mantarlaşmaya bağlı olarak öldüğü tespit edilmiştir. Gökkuşağı alabalığı kuluçkahanelerinde sürdürülebilir bir üretim için döllenmiş yumurtaların ilk günden itibaren günde en az bir kez 2 ml/l dozunda polivinil pirolidon-iyot ile 10 dakika süreyle dezenfekte edilmesi gerektiği belirlenmiştir.

Glutamine Synthetase Contributes to the Regulation of Growth, Conidiation, Sclerotia Development, and Resistance to Oxidative Stress in the Fungus Aspergillus flavus.

The basic biological function of glutamine synthetase (Gs) is to catalyze the conversion of ammonium and glutamate to glutamine. This synthetase also performs other biological functions. However, the roles of Gs in fungi, especially in filamentous fungi, are not fully understood. Here, we found that conditional disruption of glutamine synthetase (AflGsA) gene expression in Aspergillus flavus by using a xylose promoter leads to a complete glutamine deficiency. Supplementation of glutamine could restore the nutritional deficiency caused by AflGsA expression deficiency. Additionally, by using the xylose promoter for the downregulation of AflgsA expression, we found that AflGsA regulates spore and sclerotic development by regulating the transcriptional levels of sporulation genes abaA and brlA and the sclerotic generation genes nsdC and nsdD, respectively. In addition, AflGsA was found to maintain the balance of reactive oxygen species (ROS) and to aid in resisting oxidative stress. AflGsA is also involved in the regulation of light signals through the production of glutamine. The results also showed that the recombinant AflGsA had glutamine synthetase activity in vitro and required the assistance of metal ions. The inhibitor molecule L-α-aminoadipic acid suppressed the activity of rAflGsA in vitro and disrupted the morphogenesis of spores, sclerotia, and colonies in A. flavus. These results provide a mechanistic link between nutrition metabolism and glutamine synthetase in A. flavus and suggest a strategy for the prevention of fungal infection.

Chitosan coated - biogenic silver nanoparticles from wheat residues as green antifungal and nanoprimig in wheat seeds

In this study, chitosan-coated biogenic silver nanoparticles (AgNP-CH) were obtained through green chemistry by recycling wheat crop leaf residues. The nanoparticles were characterized by UV-VIS spectroscopy, and total reflectance-Fourier transform infrared spectroscopy confirmed the nanoparticle formation, and the incorporation of chitosan surrounding silver nanoparticles. The size and morphology of nanoparticles were evaluated by microscopy techniques, showing a size range of 2–10 nm, with spherical shape and narrow distribution. The antifungal assay indicated a higher antimicrobial activity showing values of minimum inhibitory concentrations of 41.7 μg/mL against Fusarium oxysporum, and 208.37 μg/mL for Aspergillus niger, A. versicolor and A. brasiliensis. Finally, non-phytotoxic effects were observed in germination assays at early plant stage of development, and an increase in chlorophyll levels were observed at the doses tested with AgNP-CH. Thus, the use of AgNP-CH could be a potential alternative for the prevention of fungal infections in cereals in the early stages of wheat crop development.

Clinical characteristics and prediction model of early death in severe/very severe aplastic anemia with immunosuppressive therapy

Objective: Early death (ED) characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia (SAA/VSAA) treated with intensive immunosuppression therapy and establish an ED prediction model. Methods: The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin (ATG) at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected. The characteristics and causes of ED within 90 days were analyzed retrospectively. Cox proportional hazards model was used to screen the ED risk factors and build a prediction model. Results: Only 19 patients (8.2% ) developed ED with a median time of 24 (3-85) days among the 232 patients with SAA/VSAA who received ATG treatment. The main cause of ED was infection (84.2% ) , followed by cerebral hemorrhage (10.5% ) . Multivariate analysis showed that VSAA (HR=15.359, 95% CI 1.935-121.899, P=0.010) , fungal infection prevention by posaconazole (HR=0.147, 95% CI 0.019-1.133, P=0.066) , lymphocyte count (LYM) ≤ 0.5×10(9)/L (HR=3.386, 95% CI 1.123-10.206, P=0.030) , and PLT ≤ 5×10(9)/L (HR=8.939, 95% CI 1.948-41.019, P=0.005) were ED's independent influencing factors. To build a clinical prediction model, VSAA, fungal infection prevention by posaconazole, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L were scored with 3, -2, 1, and 2, respectively. The integral model AUC=89.324 (95% CI 80.859-97.789) . The ED risk in patients with a score ≥ 3 was 23.1 (95% CI 5.3-100.2) times that in patients with a score<3. Conclusion: ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG. VSAA, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

Molecular study and antifungal susceptibility profile of Trichophyton rubrum and Trichophyton mentagrophytes strains isolated from lesions of humans and cattle.

Monitoring of contagious diseases is important to advance our knowledge of their epidemiology and to enable more impressive investigation and prevention efforts. This study aimed to examine antifungal drug susceptibility and molecular analysis of clinical isolates of Trichophyton rubrum and Trichophyton mentagrophytes in humans and cattle. A total of 400 patients and 500 cattle were evaluated in this study. Dermatophytosis was confirmed in cases by direct microscopy and culture methods. Antifungal drug susceptibility profiles, MIC50, and MIC90 of isolates were determined using the broth microdilution method. Multiplex-PCR, RAPD PCR, and sequencing methods were used for the genetic analysis of virulence genes and the ITS1 and ITS2 regions, respectively. A total of 175 patients and 120 cattle were diagnosed with dermatophytosis. Dermatophytes showed a remarkable rate (30%) of terbinafine resistance. T. mentagrophytes showed lower susceptibility than T. rubrum (MIC50 =16 μg/mL). Strains harboring Mep1, Mep2, and Mep4 genes had the highest frequency among all genotypes. A RAPD-PCR dendrogram divided T. mentagrophytes and T. rubrum strains into three and six groups, respectively. A notable rate of resistance to terbinafine in isolated dermatophytes was reported in this study. Examination of RAPD-PCR results showed that T. rubrum strains had higher genetic diversity than T. mentagrophytes. Genetic monitoring of dermatophytes must be considered an important factor in providing fungal infection prevention and treatment approaches.

ICU environmental surfaces are a reservoir of fungi: species distribution in northern Italy

Preventing and reducing nosocomial infections is a public health goal. Concern about healthcare-associated fungal infections has increased in recent years due to the emergence and spread of new pathogens, increasing antifungal resistance and outbreaks in hospital settings. To investigate the presence of medically relevant fungal species on environmental surfaces in 12 intensive care units of eight hospitals in Milan, Italy. Environmental samplings, using contact plates on surfaces near bed stations and medical workstations, were conducted between November 2019 and January 2020. Fungi isolated were identified, and some were tested invitro for antifungal susceptibility. In total, 401 environmental samples were collected from 61 bed stations and 17 medical workstations. Positive samples were found in all hospitals except one, with positivity rates ranging from 4% to 24.2%. Filamentous fungi were found mainly on infusion pumps (23.2%) and patient tables (21.2%), whereas yeasts were found mainly on computers (25%) and floors (10.9%). Fungi were isolated from 12% of total samples. Filamentous fungi, mainly Aspergillus fumigatus, grew in 70.8% of positive samples, and yeasts grew in 27.1%, mainly Candida parapsilosis (42.8%) and Candida glabrata (28.6%). Fungi were detected near patients' beds and on surfaces at workstations, indicating potential for environment-to-patient, patient-to-patient and healthcare worker-to-patient transmission. Surveillance in hospital settings through environmental sampling may be an important component of fungal infection prevention.

Isolation, Identification and Speciation of Dermatophyte Infection in a Tertiary Care Hospital

Introduction: The common fungal infections seen in human are Dermatophytoses. They are capable to invade keratinized tissues. Mainly affect the skin, hair and nail, therefore, called as keratinophilic fungi. Dermatophytes falls under three Genus known as Trichophyton, Epidermophyton and Microsporum collectively called as dermatophytes. Unlike bacteria fungi are multicellular and are having different and specific morphology. They can be grown in the artificial media at room temperature and in human body temperature Objective: Isolation and identification of fungi will help to select the appropriate antifungal management of dermatophyte infection. Methodology: For isolation identification and speciation of dermatophytes the clinical specimens should be collected from skin, nail and hair which are obtained from patients attending the Dermatology department. Over a period of one and half year. A total no of 180 samples are collected from the patients. Samples are examined under direct microscopy in 10%, and 40% KOH. The morphology of the fungal hyphae is studied. Samples are also inoculated onto SDA and incubated at 25C and 37C for14 days. The colony characteristics and microscopic morphology in LPCB preparations are also examined. Based on the results the fungiare identified. Further speciation was carried out by using hair perforation test and Urease test. Results: All the 180 clinically suspected specimen of dermatophytes when examined results showed that most of the cases are seen between the age group of 21and 30 years. The predominant isolates belong to the genus Trichophyton (96.70%). Among the Trichophyton species mentagrophytes is the most common isolate (58.24%) T. rubrum is the next important species isolated. Conclusion: Early identification of the dermatophytes and timely given therapy will be of greater value in the prevention of fungal infection.

Role of gene sequencing for the diagnosis, tracking and prevention of fungal infections

The precise diagnosis of fungi is utmost important owing to the morbidity and mortality caused especially in various susceptible hosts. Among the diagnostic methods though the phenotypic methods are being routinely used among laboratories but they have inherent hindrances of being tedious, time-consuming and entail experience. These roadblocks acting as a major obstacle in precise identification of fungi, underlined the requisite for implementation of genotypic methods for routine diagnosis. Since sequencing forms the cornerstone of molecular identification of fungi, many sophisticated modalities and platforms have been developed. The role of fungal sequencing isn't limited merely to the identification of known fungal species in routine laboratory, but is of utmost significance in deciphering the emerging pathogenic and saprophytic fungal species that have the potential to infect humans. It was with the use of these sequencing techniques that the complex fungal nomenclature based on presence or absence of sexual form of the fungus, could be simplified and unified effort led to adoption of 'one-fungus--one-name' rule. Panfungal PCR targeting 28S rRNA when used in conjunction with sequencing for detection of etiological agents in patients with invasive fungal disease (IFD) from deep tissue samples has shown encouraging results. Though many sequencing modalities are available, an ideal diagnostic platform is yet awaited to meet the diversity of fungal infections in initial stages itself. The early diagnosis enables the clinician to administer appropriate therapy as and when required. The same helps in delimiting the undesired affects of antifungals as well as indirectly help in antimicrobial stewardship as well.

Voice Prosthesis Coated with Sustained Release Varnish Containing Clotrimazole Shows Long-Term Protection against Candida albicans: An InVitro Study.

Fungal biofilm formation on voice prosthesis (VP) is a major health problem that requires repeated replacement of the prosthesis. Candida albicans is one of the pathogens that frequently inhabits the VP. We proposed that coating VPs with sustained-release varnish (SRV) containing clotrimazole (CTZ) might prevent fungal biofilm formation. The long-term antifungal activities of SRV-CTZ- versus SRV-placebo-coated VPs was tested daily by measuring the inhibition zone of C. albicans seeded on agar plates or by measuring the fungal viability of C. albicans in suspension. The extent of biofilm formation on coated VPs was analyzed by confocal microscopy and scanning electron microscopy. We observed that SRV-CTZ-coated VPs formed a significant bacterial inhibition zone around the VPs and prevented the growth of C. albicans in suspension during the entire testing period of 60 days. Fungal biofilms were formed on placebo-coated VPs, while no significant biofilms were observed on SRV-CTZ-coated VPs. HPLC analysis shows that CTZ is continuously released during the whole test period of 60 days at a concentration above the minimal fungistatic concentration. In conclusion, coating VPs with an SRV-CTZ film is a potential effective method for prevention of fungal infections and biofilm formation on VPs.

2021 BSH guidelines for the management of adult myelodysplastic syndromes: a practical approach to a challenging disease.

Myelodysplastic syndromes (MDS) are a group of haematological malignancies with extremely variable biologic, genetic and clinical characteristics.1 The outcome of MDS patients is very heterogeneous, some having a near-normal life expectancy while others die within a few months of their diagnosis. The median age of patients at diagnosis is advanced, ranging between 70 and 75 years, thus further complicating the management of these complex syndromes, since non-haematological comorbidities frequently coexist in the elderly and tolerability of treatments is limited.2 Given the heterogeneity of the disease pathobiology and the highly variable disease course, prognostic risk stratification is of crucial importance in clinical decision-making.3 To drive appropriate counselling and individualisation of treatment decisions, several prognostic scoring systems based on clinical and haematological parameters have been developed. Principal scoring systems currently used in Europe are the International Prognostic Scoring System (IPSS), and the revised IPSS (R-IPSS), which are based on the evaluation of peripheral blood cytopenias, bone marrow blast count and cytogenetic features.4 In daily practice, reliability of these scores is limited by the variability of morphological evaluation and, less frequently, by non-informative cytogenetic findings in a proportion of patients. Moreover, other factors including the clonal mutational status have been reported to influence the prognosis of MDS patients, and to affect the clinical outcome.5, 6 In any case, diagnostic procedures and evaluation of prognosis are not covered by these guidelines as they will be published in a separate British Society for Haematology (BSH) document. Unlike the previous edition, the 2021 BSH guidelines also do not include recommendations for CMML, for which dedicated guidelines will follow. The 2021 updated BSH guidelines for the Management of Adult Myelodysplastic Syndromes provide clear, simple and practical recommendations to approach patients with such a challenging diagnosis.7 Given the heterogeneity of the disease, the importance of establishing an individual risk-adapted treatment strategy is crucial; nonetheless, transfusion requirements and infectious complications are common to almost all patients, sooner or later. The guidelines first exhaustively describe the supportive measures that should be adopted with most patients; in particular, recommendations are reported the for prevention of fungal infection, a common complication in neutropenic patients, and for transfusion thresholds and policies to be adopted to improve patient quality of life (QoL) on the one hand, saving blood products on the other. Then, individual planning of therapeutic options is described extensively, also by means of simplified algorithms. Although standard care for MDS is constantly changing, recommendations for the initial treatment choice are still based on IPSS and R-IPSS risk evaluation, and, importantly, on patient’s preference. Therapeutic measures for most lower risk patients aim to decrease the transfusion burden and improve QoL, whereas recommendations for higher risk patients aim to prolong their life. This distinction is clearly represented in these guidelines; for each group updated treatment strategies are reported, some reflecting the 2014 BSH document. Still relevant is the recommendation that the initial MDS diagnosis should be discussed by a multidisciplinary team, including a transplantation expert, as allogeneic transplantation remains the only potentially curative option. Worthy of note, in this setting recommendations for cytoreduction in advanced MDS with hypomethylating agents (HMA) or chemotherapy before transplant are still debated, although inferior survival outcomes for patients with excess BM blasts (> 5%) at the time of transplant have been reported. Moreover, it is important that clinicians review MDS cases regularly in multidisciplinary meetings to determine if a patient can become a possible transplant candidate and/or can possibly take part in a clinical trial. Patients’ details should also be made available to national and international dedicated registries, ‘to maximize information about the patient’s history and treatment of MDS in order to benefit future patients’. In general, the guidelines are proposed to improve the quality of care of patients as well as to help physicians in their daily practice. The BSH guidelines for the management of MDS represent a timely update and make a valid contribution for the diagnosis and treatment of this heterogeneous group of blood disorders.