Fungal Infection Rates Research Articles

Nutritional symbionts enhance structural defence against predation and fungal infection in a grain pest beetle.

ABSTRACTMany insects benefit from bacterial symbionts that provide essential nutrients and thereby extend the hosts’ adaptive potential and their ability to cope with challenging environments. However, the implications of nutritional symbioses for the hosts’ defence against natural enemies remain largely unstudied. Here, we investigated whether the cuticle-enhancing nutritional symbiosis of the saw-toothed grain beetle Oryzaephilus surinamensis confers protection against predation and fungal infection. We exposed age-defined symbiotic and symbiont-depleted (aposymbiotic) beetles to two antagonists that must actively penetrate the cuticle for a successful attack: wolf spiders (Lycosidae) and the fungal entomopathogen Beauveria bassiana. While young beetles suffered from high predation and fungal infection rates regardless of symbiont presence, symbiotic beetles were able to escape this period of vulnerability and reach high survival probabilities significantly faster than aposymbiotic beetles. To understand the mechanistic basis of these differences, we conducted a time-series analysis of cuticle development in symbiotic and aposymbiotic beetles by measuring cuticular melanisation and thickness. The results reveal that the symbionts accelerate their host's cuticle formation and thereby enable it to quickly reach a cuticle quality threshold that confers structural protection against predation and fungal infection. Considering the widespread occurrence of cuticle enhancement via symbiont-mediated tyrosine supplementation in beetles and other insects, our findings demonstrate how nutritional symbioses can have important ecological implications reaching beyond the immediate nutrient-provisioning benefits.

The prevalence of pulmonary aspergillosis in coronavirus disease 19 (COVID-19) patients in Shebin El-Kom teaching hospital in Egypt

BackgroundA high rate of invasive fungal infection has been demonstrated among critically COVID-19 ill patients admitted to the ICU, with high odds of mortality. Simple and rapid risk stratification methods are mandatory to recognize severe patients.ObjectivesThe aims was to study the prevalence of invasive fungal infection in Corona virus disease 19 (COVID-19) patients, the effect of some inflammatory markers that lead to the development and progression of invasive fungal infection and to assess the value of PCR in early and rapid detection of invasive fungal infection in immune compromised patients with COVID-19.MethodsThis study was conducted at the period from October 2020 to October 2021 on two groups classified as following: Group I: included 120 immuno-compromised inpatients (2-80 years), (68 males and 52 females) from ICUs. Group II: included 40 outpatient's COVID-19 (4 – 56 years). All basic laboratory biomarkers at time of admission were recorded.ResultsOf this study showeda highly significant increase in neutrophil/ lymph, IL6,CRP, D-dimer and malondialdhyde (MDA) in COVID-19 patients in ICU compared with outpatient one with P value < 0.001). No significant difference between them in LDH, ferritin and procalcitonine. The most common isolated organisms (167 isolates) from group I (230 samples from 120 patients) were bacterial spp. (111/167, 66.5%)followed by Candida spp. (30, 17.9%), Aspergillus spp. (11, 6.6%) while mucormycosis was 5 isolates (3%) and associated bacterial infection represented 5.9%of all. Out of 120 patients suspected of complaining of BSI 17 (14.1%) of them proved to be fungemia. The most common isolated yeast was Candida spp. (11/120, 9.1%) followed by Aspergillus spp. (6/120, 5%). While out of 20 patients (group I) suspected of complaining of eye infections, mucormycosis was represented by 5/20 (25%). Fungaemia was detected by PCR and blood culture in 50 high risk ICU patients was 22/50 (44%) and 17/50 (34%) respectively. PCR is more sensitive than blood culture, as blood culture failed to detect 5 cases of fungemia with a significant difference (P-value <0.05).ConclusionIncrease in neutrophil/lymph, IL6,CRP, D-dimer and MDA in COVID-19 ICU patients compared with outpatients may be significant biomarkers used to detect severity of disease in ICU patients and monitor treatment. Also decrease in immunity as results of corticostorides admission, lead to presence of fungaemia in some patients in ICU.

Analysis of Pathogenic Bacteria of Mooren’s Ulcer and T Lymphocyte Activation

To analyze the distribution and types of pathogenic bacteria of Mooren’s ulcer and the activation mechanism of T lymphocytes to provide reference for the treatment of Mooren’s ulcer, 156 patients (162 eyes) who were in the hospital were rolled into the observation group. During the same period, 134 healthy people were rolled into the control group. The distribution of infectious pathogens in the observation group was identified. Then, flow cytometry was adopted to separate and detect the peripheral blood lymphocytes of patients, and RT-PCR was used to detect levels of the transcription factor T-bet, GATA-3, and Stat5 in peripheral blood mononuclear cells (PBMCs). It was found that fungal pathogens accounted for 43.59%; the bacterial infection rate was 40.38%. In the observation group, the CD4, CD8, and C25 were expressed more (P &lt; 0.01), and the CD45 and CD45R were expressed less than the control group (P &lt; 0.05); the proportion of Th1 cells was obviously higher (P &lt; 0.01); the expression of T-bet and GATA-3 was obviously higher (P &lt; 0.05), the percentage of HLA-DR in CD4+ and HLA-DR, CD-25, and CD69 in CD8+ positive cells was obviously higher (P &lt; 0.05). In conclusion, fungal infection rate of Mooren’s ulcer is relatively high, peripheral blood T cells and their subgroups are abnormally activated, and T cell activation is related to the pathogenesis of Mooren’s ulcer.

A rare presentation of rhinosporidiosis on buccal mucosa − a case report

Introduction: Rhinosporidiosis is a chronic mucocutaneous infection caused by Rhinosporidium seeberi, which mainly affects the mucus membranes of the nose, oropharynx, skin, eyes, and genital mucosa. The purpose of this case report was to illustrate the importance of clinicians in understanding the unusual incidence of this fungal infection, clinical presentation, treatment modalities, and recurrence rate. Observations: A clinical case report showed rare occurrence of rhinosporidiosis in the lower third of the face. The lesion was surgically excised by electrocauterization at its base. Commentaries: The patient showed no signs of recurrence even after 3 years of follow-up. Further research should be carried out to analyze the role of genetic predisposition in causing zoonotic infection. Conclusion: Rhinosporidiosis should also be considered as the differential diagnosis when facial swelling is encountered.

Vacuolar Protein-Sorting Receptor MoVps13 Regulates Conidiation and Pathogenicity in Rice Blast Fungus Magnaporthe oryzae.

Magnaporthe oryzae (synonym Pyricularia oryzae) is a filamentous fungal pathogen that causes major yield losses in cultivated rice worldwide. However, the mechanisms of infection of M. oryzae are not well characterized. The VPS13 proteins play vital roles in various biological processes in many eukaryotic organisms, including in the organization of actin cytoskeleton, vesicle trafficking, mitochondrial fusion, and phagocytosis. Nevertheless, the function of the Vps13 protein in plant pathogenic fungi has not been explored. Here, we analysed the biological functions of the Vps13 protein in the development and pathogenicity of M. oryzae. Deletion mutants of MoVps13 significantly reduced the conidiation and decreased the rate of fungal infection on hosts. Moreover, the loss of MoVps13 resulted in defective cell wall integrity (CWI) and plasma membrane (PM) homeostasis when treated with chemicals for inducing cell wall stress (200 mg/mL Congo Red or 0.005% SDS) and sphingolipid synthesis inhibitors (2 μM myriocin or 2 μM amphotericin B). This indicated that MoVps13 is also involved in cell wall synthesis and sphingolipid synthesis. Through immunoblotting, autophagic flux detection, co-localization, and chemical drug sensitivity assays, we confirmed the involvement of Movps13 in ER-phagy and the response to ER stress. Additionally, we generated the C-terminal structure of MoVps13 with high accuracy using the alphaflod2 database. Our experimental evidence indicates that MoVps13 is an important virulence factor that regulates the pathogenicity of M. oryzae by controlling CWI, lipid metabolism and the ER-phagy pathway. These results have expanded our knowledge about pathogenic fungi and will help exploration for novel therapeutic strategies against the rice blast fungus.

Invasive fungal infections in neonates: a review.

Invasive fungal infections remain the leading causes of morbidity and mortality in neonates, especially preterm and very low birth weight infants. Most invasive fungal infections are due to Candida or Aspergillus species, and other fungi are increasingly reported and described. Appropriate identification and treatment are required to augment activity and reduce the toxicity of antifungal drugs. Successful use of antifungals in the vulnerable neonatal population is important for both prevention and treatment of infection. Strategies for prevention, including prophylactic antifungal therapy as well as reducing exposure to modifiable risk factors, like limiting antibiotic exposure, discontinuation of central catheters, and hand hygiene are key techniques to prevent and decrease rates of invasive fungal infections. In conclusion, this is a review of the most common causes, prevention strategies, prophylaxis, and treatment of invasive fungal infections in neonates.

Antifungal Prophylaxis After Lung Transplantation: Where Are We Now?

Lung transplantation is an important treatment option for various end-stage lung diseases. However, survival remains limited due to graft rejection and infections. Despite that fungal infections are frequent and carry a bad prognosis, there is currently no consensus on efficacy, optimal drug, route, or duration of antifungal prophylaxis. This narrative review summarizes current strategies for antifungal prophylaxis after lung transplantation. English language articles in Embase, Pubmed, UptoDate, and bibliographies were used to assess the efficacy and safety of available antifungal agents for prophylaxis in adult lung transplant recipients. Overall, there are limited high-quality data. Universal prophylaxis is more widely used and may be preferable over targeted prophylaxis. Both formulations of inhaled amphotericin B and systemic azoles are effective at reducing fungal infection rates, yet with their own specific advantages and disadvantages. The benefit of combination regimens has yet to be proven. Considering the post-transplant timing of the onset of fungal infections, postoperative prophylaxis during the first postoperative months seems indicated for most patients. Based on existing literature, universal antifungal prophylaxis with inhaled amphotericin B and systemic voriconazole for at least 3-6 mo after lung transplantation may be advisable, with a slight preference for amphotericin B because of its better safety profile.

Antifungal Prophylaxis: Impact on Outcomes of Newly Diagnosed AML Patients Treated with a Hypomethylating Agent and Venetoclax

Antifungal Prophylaxis: Impact on Outcomes of Newly Diagnosed AML Patients Treated with a Hypomethylating Agent and Venetoclax

Infection in Children with Acute Myeloid Leukemia in the Intensive Chemotherapy Period

To investigate the clinical characteristics of infection in children with acute myeloid leukemia (AML) after high intensive chemotherapy， so as to provide reference for prevention and control of infection. 56 children diagnosed as acute myeloid leukemia in our hospital from January 2016 to August 2019 were enrolled and retrospectively analyzed, the infection rate, pathogens of disease and common location of infection during the induction and consolidation period were analyzed. The total infection rate of the patients was 93.4%－96.4%, the average of serious infection rate was 16.0%(11.3%－19.6%), and the infection related mortality was 10.7%. Fever of unknown cause was the main reason of infection, while blood flow infections were the most common in severe infection, which were mainly caused by Gramnegative bacteria. The rate of fungal infection was 35.7% during chemotherapy. Children with AML shows a high incidence of infection in each stage of chemotherapy. The serious illness caused by blood flow infection and take antifungal drugs to reduce the occurrence of fungal infection in AML patients should be paid attention.

Isolation and Identification of Dermatophytes from Environmental Specimens Comparing with Species Isolated from Clinical Specimens of Scalp Infection among Sudanese Basic School, Kosti, White Nile State, Sudan -2020

Background: Tinea capitis (TC) or scalp ringworm is common in pediatric population with reported rates of infection ranging from 4% to 15 % .T.rubrum is rarely reported in countries with a temperate climate . There is always hair loss with varying degrees of scaling and erythema [1-3]. Objectives: To identify the role of soil, plant &amp; sewage in transmission of ringworm of scalp infection. This study was carried out on Kosti basic school students who suffering from ringworm of scalp (fungal infection) in White Nile state at Sudan in 2020. Methodology, Data Analyses and Results: Due to preservation of this fungal infection among school children in Kosti basic school students, a total of fifty specimens collected from different sources to determine the source of this infection in the area of study, twenty five students who suffering from ring worm of scalp and twenty five from soil, sewage, water and trees in the period between January – December -2020.The samples collected by scraping the scalp by surgical blade and removing the hair with needle and forceps from the peripheral lesion and gathered in filter paper and closed tightly,10% KOH was used to clarify and keratinized tissues. Trees samples were collected by washing the tree’s leaves and with all soil, sewage, water were collected into container. All samples were cultured on sabouroad dextrose agar medium for one week at room temperature. After growth, lactophenol cotton blue staining was used to identify depending on the colonial morphology under microscope and tolook for color, septate, aseptate hyphae, macro, micro conidia and spores. The results showed that there was 68% of isolates from soil, sewage, water and trees were matched to scalp isolates. The soil is significant one of these when Chi-square (X2) was used (P value = 0.027) that means, the source of infection among students may be due to soil transmission. Conclusion and Recommendation: Our results highlight the epidemiology of fungal infection of Kosti basic school students. Further studies are necessary to verify these findings considering the relatively high rate of fungal infection to cover all expected area with similar observation.

Characterization, Biological Activity, and Mechanism of Action of a Plant-Based Novel Antifungal Peptide, Cc-AFP1, Isolated From Carum carvi.

Due to the increasing rate of invasive fungal infections and emerging antifungal resistance, development of novel antifungal drugs has been an urgent necessity. Antifungal peptides (AFPs) have recently attracted attention due to their unique ability to evade drug-resistant fungal pathogens. In this study, a novel AFP, Cc-AFP1, with a molecular weight of ~3.759 kDa, was isolated from Carum carvi L., purified by ammonium sulfate precipitation and reversed-phase HPLC and finally identified by sequence analysis using Edman degradation. Peptide sequence analysis revealed a fragment of 36 amino acid residues as RVCFRPVAPYLGVGVSGAVRDQIGVKLGSVYKGPRG for Cc-AFP1 with a net charge of +5 and a hydrophobicity ratio of 38%. The antifungal activity of Cc-AFP1 was confirmed against Aspergillus species with MIC values in the range of 8–16 µg/ml. Cc-AFP1 had less than 5% hemolytic activity at 8–16 µg/ml on human red blood cells with no obvious cytotoxicity against the HEK293 cell line. Stability analysis showed that the activity of Cc-AFP1 was maintained at different temperatures (20°C to 80°C) and pH (8 to 10). The results of a propidium iodide uptake and transmission electron microscopy showed that the antifungal activity of Cc-AFP1 could be attributed to alteration in the fungal cell membrane permeability. Taken together, these results indicate that Cc-AFP1 may be an attractive molecule to develop as a novel antifungal agent combating fungal infections cause by Aspergillus species.

Combination of a triple wavelength (650 nm, 810 nm, and 915 nm) class IV laser system and local mechanical abrasion in the treatment of chronic toenail onychomycosis: an uncontrolled prospective pilot study.

BackgroundToenail onychomycosis is a frequent fungal infection that is difficult to treat, especially in elderly patients. Diverse local and systemic antifungal treatments are available with variable results. Recently, different laser systems have been proposed for the treatment of onychomycosis, among them a class IV laser system adopting three different wavelengths, that is, 650, 810, and 915 nm (K‐Laser Cube 3TM).ObjectivesThis prospective pilot study aims to clarify the clinical, histopathologic, and cultural mycological efficacy of the combination of a triple wavelength laser system and local mechanical abrasion in the treatment of toenail onychomycosis.MethodsEight treatment sessions were performed involving a mechanical drill of the friable nail material followed by the laser treatment with four 2‐minute cycles per nail with a median power of 3 W providing 240 J each. Clinical exam, mycological culture, and histopathology with PAS staining of nail clips were performed at the beginning and the end of the treatment period.ResultsNine patients with 16 clinically involved nails were included in this study (median age: 55.6). Clinical improvement was noted in eight patients (89%) at the end of the treatment cycles. Initial positive cultures could be reduced from six (67%) to two (22%), P = 0.07, while histopathologic examination by PAS staining remained invariable positive in all patients (100%).ConclusionDespite clinical improvement, the combination of this laser treatment and mechanical abrasion could not reduce the fungal infection rate in affected toenails. Additional local or systemic antimycotic agents should be combined in order to avoid expected clinical recurrences.

A Unique Dual-Readout High-Throughput Screening Assay To Identify Antifungal Compounds with Aspergillus fumigatus.

ABSTRACTTreatment of invasive mold infections is limited by the lack of adequate drug options that are effective against these fatal infections. High-throughput screening of molds using traditional antifungal assays of growth is problematic and has greatly limited our ability to identify new mold-active agents. Here, we present a high-throughput screening platform for use with Aspergillus fumigatus, the most common causative agent of invasive mold infections, for the discovery of novel mold-active antifungals. This assay detects cell lysis through the release of the cytosolic enzyme adenylate kinase and, thus, is not dependent on changes in biomass or metabolism to detect antifungal activity. The ability to specifically detect cell lysis is a unique aspect of this assay that allows identification of molecules that disrupt fungal cell integrity, such as cell wall-active molecules. We also found that germinating A. fumigatus conidia release low levels of adenylate kinase and that a reduction in this background allowed us to identify molecules that inhibit conidial germination, expanding the potential for discovery of novel antifungal compounds. Here, we describe the validation of this assay and proof-of-concept pilot screens that identified a novel antifungal compound, PIK-75, that disrupts cell wall integrity. This screening assay provides a novel platform for high-throughput screens with A. fumigatus for the identification of anti-mold drugs.IMPORTANCE Fungal infections caused by molds have the highest mortality rates of human fungal infections. These devastating infections are hard to treat and available antifungal drugs are often not effective. Therefore, the identification of new antifungal drugs with mold activity is critical. Drug screening with molds is challenging and there are limited assays available to identify new antifungal compounds directly with these organisms. Here, we present an assay suitable for use for high-throughput screening with a common mold pathogen. This assay has exciting future potential for the identification of new drugs to treat these fatal infections.

Who is the culprit: Is pest infestation responsible for crop yield losses close to semi-natural habitats?

Semi‐natural habitats (SNHs) are becoming increasingly scarce in modern agricultural landscapes. This may reduce natural ecosystem services such as pest control with its putatively positive effect on crop production. In agreement with other studies, we recently reported wheat yield reductions at field borders which were linked to the type of SNH and the distance to the border. In this experimental landscape‐wide study, we asked whether these yield losses have a biotic origin while analyzing fungal seed and fungal leaf pathogens, herbivory of cereal leaf beetles, and weed cover as hypothesized mediators between SNHs and yield. We established experimental winter wheat plots of a single variety within conventionally managed wheat fields at fixed distances either to a hedgerow or to an in‐field kettle hole. For each plot, we recorded the fungal infection rate on seeds, fungal infection and herbivory rates on leaves, and weed cover. Using several generalized linear mixed‐effects models as well as a structural equation model, we tested the effects of SNHs at a field scale (SNH type and distance to SNH) and at a landscape scale (percentage and diversity of SNHs within a 1000‐m radius). In the dry year of 2016, we detected one putative biotic culprit: Weed cover was negatively associated with yield values at a 1‐m and 5‐m distance from the field border with a SNH. None of the fungal and insect pests, however, significantly affected yield, neither solely nor depending on type of or distance to a SNH. However, the pest groups themselves responded differently to SNH at the field scale and at the landscape scale. Our findings highlight that crop losses at field borders may be caused by biotic culprits; however, their negative impact seems weak and is putatively reduced by conventional farming practices.

The Spectrum of Fungal Colonization and Their Attributable Effects on Cystic Fibrosis Patients with Rare CFTR Genetic Mutations

Chronic airway colonization by bacteria and fungi is very common in CF patients, causing irreversible lung damage. It is known that rates of fungal infections are much lower than those of bacterial infections, however they can worsen the medical condition of CF patients. In this study, we identify the most common fungal species isolated from 31 adult CF patients in Qatar and analyze their correlation with lung function, pulmonary exacerbations, bronchial asthma, and pancreatic insufficiency. Mycological evaluation, as well as medical records, were reviewed for the patients regularly under the adult CF service at Hamad General Hospital in the period between 2017–2019. All CF patients included in this study carry rare CFTR mutations. The majority of those patients (n = 25) carried the c.3700A&gt;G; I1234V mutation, whereas three patients carried the heterozygous mutation (c.1657C&gt;T and c.1115A&gt;T) and the remaining three carried the homozygous mutation (c.920G&gt;A). Twenty-two of the adult CF participants (70.9%) were colonized with fungal species regardless of the type of the CFTR mutation. Candida and Aspergillus species were the most common, colonizing 81% and 45% of the patients, respectively. For Candida colonized patients, Candida dubliniensis was the most frequently reported species (55.6%), whereas Aspergillus fumigatus colonization was the most common (50.0%) among Aspergillus colonized patients. These identified fungal pathogens were associated with poor lung function, pancreatic insufficiency, and asthma in this cohort. Such colonization could possibly aggravate the most known CF complications, notably pulmonary exacerbations, asthma, and pancreatic insufficiency.

Temporal Trends in Sepsis Incidence and Mortality in Patients With Cancer in the US Population.

Few population-based studies assess the impact of cancer on sepsis incidence and mortality. To evaluate epidemiological trends of sepsis in patients with cancer. This retrospective cohort study included adults (≥20 years old) identified using sepsis-indicator International Classification of Diseases codes from the Nationwide Inpatient Sample database (2006-2014). A generalized linear model was used to trend incidence and mortality. Outcomes in patients with cancer and patients without cancer were compared using propensity score matching. Cox regression modeling was used to calculate hazard ratios for mortality rates. The study included 13 996 374 patients, 13.6% of whom had cancer. Gram-positive infections were most common, but the incidence of gram-negative infections increased at a greater rate. Compared with patients without cancer, those with cancer had significantly higher rates of lower respiratory tract (35.0% vs 31.6%), intra-abdominal (5.5% vs 4.6%), fungal (4.8% vs 2.9%), and anaerobic (1.2% vs 0.9%) infections. Sepsis incidence increased at a higher rate in patients with cancer than in those without cancer, but hospital mortality rates improved equally in both groups. After propensity score matching, hospital mortality was higher in patients with cancer than in those without cancer (hazard ratio, 1.25; 95% CI, 1.24-1.26). Of patients with sepsis and cancer, those with lung cancer had the lowest survival (hazard ratio, 1.65) compared with those with breast cancer, who had the highest survival. Cancer patients are at high risk for sepsis and associated mortality. Research is needed to guide sepsis monitoring and prevention in patients with cancer.

Epidemiology of fungal infection after hepatobiliary surgeries at National Liver Institute Hospital (Menoufia University)

Objectives To estimate the incidence rate of fungal infections after hepatobiliary surgery and identification of the risk factors. Background Candidemia and disseminated candidiasis are major causes of morbidity and mortality in hospitalized patients, especially in the ICU, the incidence of invasive candidiasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Participants and methods A prospective cohort hospital-based study was carried out at the National Liver Institute, Menoufia University. The studied group was 210 patients, all of them were examined thoroughly, their data were registered and sampled two times, one at the day of admission to be sure that they are free of fungal infection and the second was after hepatobiliary surgery. A predesigned questionnaire was used, which includes data about personal history, medical history, and suggested risk factors for fungal infections. Results In the present study, the incidence rate of fungal infection among patients who had hepatobiliary surgeries in National Liver Institute was found (45.2%) and by logistic regression analysis of data indicated that the most relevant factors for fungal infection were age (P < 0.001), antibiotic use (P < 0.05), liver disease (P < 0.05), central venous catheter (P < 0.05), urinary catheter (P < 0.05), and ICU hospitalization more than 48 h (P < 0.001). Conclusion High incidence of fungal infection after hepatobiliary surgeries is considered a great health problem. The main risk factors of fungal infection are low immunity, chronic disease, diabetes, hepatitis B virus and/or hepatitis C virus infection, cancer, anemias, organ transplantation, blood transfusion, had central venous catheter, intravenous catheter, had abdominal drain, urinary catheter, parenteral nutrition, history of past operations, and hospitalized in the ICU more than 48 h.

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study

Background and AimsRisankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study.MethodsEnrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks.ResultsSixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%].ConclusionsLong-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn’s disease, with no new safety signals. Clinical trial registration number: NCT02513459

Caspofungin combined with hormones as preemptive therapy of chemotherapy-induced disseminated candidiasis in a patient

Disseminated candidiasis (DC) arising from nosocomial fungal infection is a life-threatening complication in critically ill, nonneutropenic patients. The overall nosocomial fungal infection rate in United States hospitals doubled from 1980–1990. Until recently, amphotericin B was the only agent available for the treatment of life-threatening candidal infections, but its use is plagued by toxicities including nephrotoxicity and infusion-related reactions such as rigors and hypotension. The availability of fluconazole, which is regarded more much less toxic than amphotericin B, prompted a surge in research to determine if it is as efficacious in the management of candidemia and hematogenously disseminated candidiasis. Complicating the interpretation of studies is the broad range of infection severity, from candidemia that may be transient and self-limiting to life-threatening hematogenously disseminated candidiasis. This study has used the models of Artificial neural network (ANN) and Support Vector regression (SVR) to accurately assess the clinical trials comparing fluconazole and amphotericin B demonstrate the efficacy of fluconazole for catheter-associated candidemia in critically ill patients when the likely pathogen is Candida albicans. As a result, Amphotericin B should remain the first-line agent for the management of candidemia and hematogenously disseminated candidiasis in all other patients. Also, SVR could accurately assess the efficacy of fluconazole for catheter-associated candidemia in critically ill patients.

Investigational Agents for the Treatment of Resistant Yeasts and Molds.

Purpose of ReviewThis review summarizes the investigational antifungals in clinical development with the potential to address rising drug resistance patterns. The relevant pharmacodynamics, spectrum of activity, preclinical studies, and latest clinical trial data are described.Recent FindingsAgricultural and medicinal antifungal use has been selected for inherently drug-resistant fungi and acquired resistance mechanisms. The rates of fungal infections and immunocompromised populations continue to grow as few new antifungals have hit the market. Several agents with the potential to address the emergence of multidrug-resistant (MDR) molds and yeasts are in clinical development.SummaryEvolved formulations of echinocandins, polyenes, and triazoles offer less toxicity, convenient dosing, and greater potency, potentially expanding these classes’ indications. Ibrexafungerp, olorofim, oteseconazole, and fosmanogepix possess novel mechanisms of actions with potent activity against MDR fungi. Successful clinical development is neither easy nor guaranteed; thus, perpetual efforts to discover new antifungals are needed.