Treatment Of Invasive Aspergillosis Research Articles

Age difference of patients with and without invasive aspergillosis: a systematic review and meta-analysis.

Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies. We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity. A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I2 = 26.1%) than those without the disease (p < 0.0001). No significant moderators could explain the observed heterogeneity in age difference. However, subgroup analysis revealed that age differences were more pronounced within particular patient groups compared to others. For example, patients with and without IA who had primary severe lung infections exhibited a greater difference in mean age than other patient cohorts. Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes.

Utility and Drawbacks of Biomarkers in Diagnosis of Invasive Aspergillosis in Critically Ill Patients.

Background: Hematopoietic stem cell transplant recipients, patients with hematological malignancies, and individuals experiencing neutropenia after anti-cancer medication are at high risk of developing invasive aspergillosis (IA). Furthermore, IA is being seen more frequently in different groups of people, including those receiving solid organ transplants, individuals with solid tumors or autoimmune disorders, and patients in intensive care units. High death rates are linked to diagnostic delays. The purpose of this study is to give a summary of the available data regarding the effectiveness of various tests of biomarkers and to talk about their benefits, limitations, and interpretation in a range of patient categories. Methods: We searched the published English language literature using MEDLINE and EMBASE databases from January 2010 to October 2023. All studies about biomarker testing for the diagnosis of IA were included in the review. Results: As valuable supplementary instruments for the early identification of IA, biomarker detection tests may play a part in the diagnosis of IA and tracking treatment response. Nevertheless, there are differences between patient populations and these biomarkers’ sensitivity and specificity are not at their best. So, biomarker testing should be targeted at the right population and the right situation to offer the optional benefit in the approach of IA diagnosis and management. Conclusion: Within the context of various clinical samples (serum, bronchoalveolar lavage fluid, cerebrospinal fluid), as well as distinct patient groups (once-hematological patients, recipients of solid organ transplants, and other patients at risk of IA), this review examines the importance, clinical utility and drawbacks of biomarkers testing for the diagnosis of IA in the critically ill patients.

Antifungal Therapies for Aspergillus spp.: Present and Future.

Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug-drug interactions, pharmacokinetic variability, and emerging resistance. While the echinocandins are safe agents and may have a role in combination therapy, they are unproven as monotherapy. Amphotericin B preparations are toxic and require intensive monitoring. Finally, aspergillosis continues to be a disease conferring substantial morbidity and mortality, and clinical trials have not identified a therapeutic approach clearly associated with improved outcomes. As a result, there is a great need for new options in the treatment of invasive aspergillosis. Ideally, such options would be safe, have high oral bioavailability, have favorable pharmacokinetics to sequestered sites and retain activity against azole-resistant isolates. Reassuringly, there is a robust pipeline of novel therapies in development. Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis. Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.

Efficacy and safety of voriconazole in the treatment of invasive pulmonary aspergillosis in patients with liver failure: study protocol for a randomized controlled clinical trial

BackgroundAcute-on-chronic liver failure (ACLF) is a common clinical type of liver failure, and patients with acute-on-chronic liver failure are prone to fungal infections, especially the increasing incidence of invasive pulmonary aspergillosis (IPA). Voriconazole is recommended as the first-line antifungal agent in the treatment of invasive aspergillosis; however, no recommendation has been given for patients with severe liver cirrhosis (Child–Pugh C) and liver failure. This trial aims to examine the therapeutic effects and safety of voriconazole in the treatment of IPA in patients with liver failure.MethodsThis study is a non-double-blind randomized controlled trial. The 96 eligible acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis will be randomly assigned to receive either the optimized voriconazole regimen or the recommended voriconazole regimen for patients with mild to moderate liver cirrhosis (Child–Pugh A and B), at a 1:1 ratio, with an 8-week follow-up period. The antifungal efficacy of voriconazole will be the primary outcome measure. Plasma voriconazole trough concentration, the laboratory examination (CRP, PCT, ESR, etc.), chest CT, adverse events, and mortality at week 4 and 8 will be the secondary outcome measures.DiscussionThis trial aims to demonstrate the efficacy and safety of voriconazole in the treatment of IPA in patients with liver failure, which is expected to provide a reference for scientific optimization of voriconazole regimens and a realistic basis for the standardized treatment of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis.Trial registrationThe trial was registered with the Chinese Clinical Trial Registry, ChiCTR2100048259. Registered on 5 July 2021.

In vitro and in vivo antimicrobial effects of domiphen combined with itraconazole against Aspergillus fumigatus

Aspergillus fumigatus, a prevalent saprophytic fungus in the atmosphere, is known to rapidly induce severe invasive aspergillosis (IA) upon inhalation of its conidia by humans or animals. The mortality rate associated with IA exceeds 50%. The misuse of antifungal agents has contributed to the emergence of numerous highly pathogenic drug-resistant strains of A. fumigatus. Our study found that the combination of domiphen and itraconazole had sound synergistic antimicrobial effects against wild-type and itraconazole-resistant A. fumigatus in vivo and in vitro through MIC, FIC, plate inoculation, growth curve experiments, and Galleria mellonella infection model. Drug cytotoxicity and pharmacological tests for acute toxicity assays demonstrated that both itraconazole and domiphen showed minimal cytotoxicity and good biocompatibility. The transcriptome sequencing experiment demonstrated that domiphen exerted a suppressive effect on the expression of various genes, including those involved in drug efflux, redox regulation, and cellular membrane and cell wall remodeling. The present investigation explores the synergistic antimicrobial mechanisms of domiphen and itraconazole, encompassing three key aspects: (i) domiphen inhibited the efflux of itraconazole by reducing the expression of drug efflux-related genes, (ii) the combination has good ability to disrupt the cell membrane and cell wall, (iii) the combination also can remove biofilm more effectively. In summary, the utilization of domiphen as a synergist of itraconazole exhibited disruptive effects on the biofilm, cell wall, and cell membrane of A. fumigatus. This subsequently led to a modified distribution of itraconazole within the fungal organism, ultimately resulting in enhanced antifungal efficacy. The results of this study may provide a new therapeutic strategy for the treatment of IA caused by drug-resistant A. fumigatus.

ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

Real-World, Multicenter Case Series of Patients Treated with Isavuconazole for Invasive Fungal Disease in China.

The incidence of invasive fungal disease (IFD) has increased significantly, and IFD is a major cause of mortality among those with hematological malignancies. As a novel second-generation triazole antifungal drug offering both efficacy and safety, isavuconazole (ISA) is recommended by various guidelines internationally for the first-line treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) infecting adults. Given that it was only approved in China at the end of 2021, there is currently a lack of statistical data regarding its usage in the Chinese population. The primary objective of this report is to describe early experiences with ISA for the treatment of IFD. This was a real-world, multicenter, observational case series study conducted in China. It included patients from three centers who received ISA treatment from January 2022 to April 2023. A retrospective assessment on patient characteristics, variables related to ISA administration, the treatment response of IFD to ISA, and potential adverse events attributed to ISA was conducted. A total of 40 patients met the inclusion criteria. Among them, 12 (30%) were diagnosed with aspergillosis, 2 (5%) were diagnosed with candidiasis, 12 (30%) were diagnosed with mucormycosis, and 14 cases did not present mycological evidence. The predominant site of infection was the lungs (36), followed by the blood stream (8), sinuses (4), and respiratory tract (2). The overall response rate was 75% (30 patients), with male patients having a higher clinical response than female patients (24/24 versus 6/16, p = 0.000) and autologous stem cell transplant patients having a higher clinical response than allogeneic stem cell transplant patients (6/6 versus 4/10, p = 0.027). During the observation period, four patients experienced adverse effects associated with ISA, but none of them discontinued the treatment. Our findings suggest that ISA, a novel first-line treatment for IA and IM, is associated with a high clinical response rate, low incidence, and a low grade of adverse effects. Given the short time that ISA has been available in China, further research is needed to identify its efficacy and safety in the real world.

Diagnosis and Treatment of Invasive Aspergillosis Caused by Non-fumigatus Aspergillus spp.

With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non-fumigatus Aspergillus spp.-namely A. flavus, A. terreus, A. niger and A. nidulans-including diagnostic and therapeutic differences and similarities to A. fumigatus. A. flavus is the second most common Aspergillus spp. isolated in patients with IA and the predominant species in subtropical regions. Treatment is complicated by its intrinsic resistance against amphotericin B (AmB) and high minimum inhibitory concentrations (MIC) for voriconazole. A. nidulans has been frequently isolated in patients with long-term immunosuppression, mostly in patients with primary immunodeficiencies such as chronic granulomatous disease. It has been reported to disseminate more often than other Aspergillus spp. Innate resistance against AmB has been suggested but not yet proven, while MICs seem to be elevated. A. niger is more frequently reported in less severe infections such as otomycosis. Triazoles exhibit varying MICs and are therefore not strictly recommended as first-line treatment for IA caused by A. niger, while patient outcome seems to be more favorable when compared to IA due to other Aspergillus species. A. terreus-related infections have been reported increasingly as the cause of acute and chronic aspergillosis. A recent prospective international multicenter surveillance study showed Spain, Austria, and Israel to be the countries with the highest density of A. terreus species complex isolates collected. This species complex seems to cause dissemination more often and is intrinsically resistant to AmB. Non-fumigatus aspergillosis is difficult to manage due to complex patient histories, varying infection sites and potential intrinsic resistances to antifungals. Future investigational efforts should aim at amplifying the knowledge on specific diagnostic measures and their on-site availability, as well as defining optimal treatment strategies and outcomes of non-fumigatus aspergillosis.

Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus.

Critically ill patients have higher risk of serious fungal infections, such as invasive aspergillosis (IA) which is mainly caused by the human fungal pathogen Aspergillus fumigatus. Triazole drugs are the primary therapeutic agents for the first-line treatment of IA, which could easily cause drug resistance problems. Here, we assess the potential of AgNPs synthesized with Artemisia argyi leaf extract and domiphen as new antifungal agents to produce synergistic antimicrobial effects on Aspergillus fumigatus, and dissect possible molecular mechanisms of action. Plate inoculation assays combined with drug susceptibility test and cytotoxicity test showed that the combination of AgNPs and domiphen has synergistic antimicrobial effects on A. fumigatus with low cytotoxicity. Gene Ontology (GO) enrichment analysis showed that AgNPs and domiphen inhibit the growth of A. fumigatus by suppressing nitrate assimilation, and purine nucleobase metabolic process and amino acid transmembrane transport, respectively. When the two drugs are combined, AgNPs has epistatic effects on domiphen. Moreover, the combination of AgNPs and domiphen primarily influence secondary metabolites biosynthesis, steroid biosynthesis and nucleotide sugar metabolism of A. fumigatus via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, protein-protein interactions (PPI) analysis combined with validation experiments showed that the combination of AgNPs and domiphen could enhance the expression of copper transporter and inhibit nitrogen source metabolism. In addition, the synergistic antimicrobial effects could be enhanced or eliminated depending on exogenous addition of copper and nitrogen source, respectively. Taken together, the results of this study provide a theoretical basis and a new strategy for the treatment of IA.

In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates.

Azole resistance in Aspergillus fumigatus (Af) has become a widespread threat and a major concern for optimal management of patients with invasive aspergillosis (IA). Combination of echinocandins with azoles is an attractive alternative option for the treatment of IA due to azole-resistant Af strains. The aim of this study was to evaluate the in vitro and in vivo combination of caspofungin (CAS) with either voriconazole (VRZ) or posaconazole (PSZ). In vitro interactions were assessed by two methods, and an animal model of IA in Galleria mellonella was used for in vivo evaluation. Assessment of efficacy was based on larvae mortality. Groups of 10 larvae were infected by 3 clinical strains of Af (azole susceptible, AfS; PSZ resistant, AfR1; VRZ and PSZ resistant strain, AfR2). In vitro, combination of CAS and azoles was indifferent against AfS, and AfR2, and a synergy was found for AfR1. When compared to VRZ monotherapy, the combination of VRZ at 4 µg/larva with CAS at 4 µg/larva improved survival of AfR2-infected larvae (p=0.0066). Combination of PSZ at 4µg/larva with CAS at 4 µg/larva improved survival of AfR1-infected larvae compared to CAS (p=0.0002) and PSZ (0.0024) monotherapy. Antagonism was never observed. In conclusion, the combination of caspofungin with azoles is a promising alternative for the treatment of azole resistant strains of Af.

In vitro activity of 23 antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates

The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38-A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001 μg/ml), followed by anidulafungin (0.104 μg/ml), posaconazole (0.15 μg/ml), itraconazole (0.37 μg/ml), efinaconazole (0.5μg/ml), voriconazole (0.51 μg/ml), tavaborole (0.72 μg/ml), and amphotericin B (0.79 μg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy.

Challenges in the Treatment of Invasive Aspergillosis in Immunocompromised Children.

Invasive aspergillosis (IA) is associated with significant morbidity and mortality. Voriconazole remains the drug of choice for the treatment of IA in children; however, the complex kinetics of voriconazole in children make dosing challenging and therapeutic drug monitoring (TDM) essential for treatment success. The overarching goal of this review is to discuss the role of voriconazole, posaconazole, isavuconazole, liposomal amphotericin B, echinocandins, and combination antifungal therapy for the treatment of IA in children. We also provide a detailed discussion of antifungal TDM in children.

Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives.

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as “possible” or “probable” cases but not “proven”. Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.

Voriconazole induced periostitis

Voriconazole is a second generation broad spectrum triazole antifungal agent which is commonly used for prophylaxis and treatment of invasive aspergillosis, especially in patients with solid organ and hematopoietic stem cell transplants. One of the rare, adverse effects of long-term use is periostitis which is caused by increased circulating levels of fluoride from voriconazole metabolism with clinical findings similar to skeletal fluorosis. Given the increased use of voriconazole, it is essential to recognize periostitis as an adverse effect with prompt discontinuation of the medication improving patient outcomes and quality of life.

Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature

ABSTRACT Introduction Invasive aspergillosis is associated with high morbidity and mortality in immunocompromised patients. It is now increasingly reported in critically ill patients, including those with respiratory viral infections, such as influenza and COVID-19. Antifungal management is challenging due to diagnostic delay, adverse drug reactions, drug–drug interactions, narrow therapeutic window, and the emergence of resistance. Isavuconazole is the most recent FDA approved azole for the treatment of invasive aspergillosis, with data continuing to accumulate. Areas covered The authors review the safety and efficacy of isavuconazole in the management of invasive aspergillosis based on the currently available evidence. The authors also report on the structure, mechanism of action, pharmacokinetic properties, in vitro and in vivo studies as well as clinical safety and efficacy reports of isavuconazole since its FDA approval. Expert opinion Isavuconazole is non-inferior to voriconazole and is a safe, effective, and better tolerated option for the treatment of invasive aspergillosis. It offers several advantages over other antifungal agents, including having a better adverse event profile with respect to hepatotoxicity, neuro-visual toxicity, QTc prolongation, as well as a stable pharmacokinetic profile obviating the need for therapeutic drug monitoring. Further studies are needed to evaluate its performance in prophylaxis against invasive aspergillosis as well as in the treatment of aspergillosis in critically ill patients without underlying cancer or transplant.

Safety and Efficacy of Isavuconazole in Patients Aged 65 Years or Older with Invasive Fungal Disease: A Post-Hoc Analysis from the VITAL and Secure Studies

Background: Invasive fungal diseases (IFDs), such as invasive mucormycosis (IM) and invasive aspergillosis (IA), are life-threatening infections that remain a major cause of morbidity and mortality in a wide range of immunocompromised patients, including older individuals. During the COVID-19 pandemic, a rise in the proportion of older patients with IFDs was observed. Isavuconazole is a broad-spectrum triazole, approved for the treatment of IM and IA in adults. Here, we conducted a post-hoc analysis of two phase 3 studies to evaluate the safety and efficacy of isavuconazole specifically in patients ≥65 years with IFDs.Methods: Data from two prospective clinical trials, VITAL (NCT00634049) and SECURE (NCT00412893), were included. VITAL was a single-arm, open-label study evaluating isavuconazole for rare IFDs (mainly IM) and IA in renally-impaired patients. SECURE was a randomized, double-blind, non-inferiority study comparing isavuconazole with voriconazole for IA. Safety (adverse events [AEs] by system organ class) and efficacy (all-cause mortality through day 42 and overall responses at end of treatment [EOT]) were assessed for the ≥65 and <65 years subgroups.Results: At enrollment, 116/146 patients were <65 years and 30/146 patients were ≥65 years in VITAL, and 391/516 patients were <65 years and 125/516 patients were ≥65 years in SECURE. Baseline characteristics were mostly comparable for both subgroups across both studies and between the isavuconazole and voriconazole treatment arms in SECURE (Table 1).SafetyIn VITAL, AEs were reported in similar proportions in both subgroups (≥65 years: 100.0%; <65 years: 94.0%); with infections and infestations (≥65 years: 63.3%; <65 years: 62.1%) being the most common. Serious AEs (SAEs) were higher in the ≥65 years (76.7%) compared to the <65 years (56.9%) subgroup, although drug-related AEs had a reverse trend (≥65 years: 33.3%, <65 years: 43.1%). The most common drug-related AEs were gastrointestinal disorders (≥65 years: 13.3%; <65 years: 16.4%).In SECURE, a similar proportion of AEs was reported in both subgroups of the isavuconazole arm (≥65 years: 98.4%; <65 years: 95.4%), with gastrointestinal disorders (≥65 years: 73.0% <65 years: 66.0%) being the most common. SAEs were reported at higher rates (61.9% vs 49.0%) in the ≥65 years than the <65 years subgroup in the isavuconazole arm. Drug-related AEs were reported more frequently in both subgroups of the voriconazole arm (≥65 years: 54.8%; <65 years: 61.4%) than the isavuconazole arm (≥65 years: 44.4%; <65 years: 41.8%). Additionally, in the ≥65 years subgroup, a higher proportion of patients (cut-off difference: ≥5%) experienced drug-related cardiac disorders (isavuconazole: 6.3%; voriconazole: 0) and general disorders and administrative site conditions (9.5% vs 1.6%) in the isavuconazole arm; and drug-related psychiatric disorders (isavuconazole: 3.2%; voriconazole: 21.0%), eye disorders (3.2% vs 19.4%), and investigation abnormalities (7.9% vs 14.5%) in the voriconazole arm. In the <65 years subgroup, higher proportions of patients (cut-off difference: ≥5%) with drug-related AEs were observed only in the voriconazole arm: investigation abnormalities (isavuconazole: 10.3%; voriconazole: 19.3%), hepatobiliary disorders (2.6% vs 11.7%), psychiatric disorders (2.1% vs 8.1%), and eye disorders (3.1% vs 8.1%).EfficacyIn VITAL, all-cause mortality through day 42 was higher (30.0% vs 13.8%) and the overall response at EOT was lower (27.6% vs 46.8%) in the ≥65 years than the <65 years subgroup (Table 2).In SECURE, all-cause mortality through day 42 was similar between both subgroups and both the isavuconazole (20.6% vs 17.9%) and voriconazole (22.6% vs 19.4%) treatment arms. Overall response at EOT was lower in the ≥65 years subgroup of the isavuconazole arm (23.7% vs 39.0%) as compared to the voriconazole arm (32.0% vs 37.5%) (Table 2).Conclusions: As expected, overall, the safety and efficacy outcomes were more favorable in the <65 years compared to the ≥65 years subgroup in both studies, although, the number of patients was relatively low in the ≥65 years subgroup. In SECURE, all-cause mortality through day 42 was similar between both subgroups and treatment arms, and the safety profile favored isavuconazole in both age subgroups. [Display omitted] DisclosuresHamed: Basilea Pharmaceutica International Ltd.: Consultancy. Engelhardt: Basilea Pharmaceutica International Ltd.: Current Employment. Kovanda: Astellas Pharma Global Development, Inc.: Current Employment. Huang: Pfizer Inc: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Yan: Pfizer Inc: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Aram: Pfizer Inc: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

Aspergillosis: Emerging risk groups in critically ill patients.

The use of corticosteroids and the presence of co-morbidities such as chronic obstructive pulmonary disease, acute or chronic advanced liver disease, or severe viral pneumonia caused by influenza or Covid-19, may increase the risk of invasive aspergillosis in intensive care unit patients.

Study of Fungal Contamination Intensive Care Units of Arak Educational Hospitals and Determining Drug Sensitivity Profiles of Isolated Species

Background and Aim: Fungal infections are among the most critical and common issues for hospitalized patients, especially in intensive care units. This study aimed to determine the fungal contamination of indoor air and surfaces in sensitive wards of the Arak University of Medical Sciences educational hospitals and determine the drug susceptibility pattern of isolated species. Methods &amp; Materials: In this descriptive cross-sectional study, 63 air samples were taken from sensitive hospital wards using the one-stage Anderson method, and 63 surfaces samples were taken using wet cotton swabs and cultured in saprodextrose agar medium containing chloramphenicol. Identification of the genus and, as far as possible, the species of fungi was performed using the culture method on the slide. Drug susceptibility testing was performed on isolated species by broth microdilution method (CLSI-M38A2 standard). Ethical Considerations: This study was approved by the Research Ethics Committee at Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1395.315). Results: From the total samples, 18 species of fungi were isolated. These included: Aspergillus niger (8), Aspergillus flavus (4), Aspergillus fumigatus (2), Rhizopus spp. (2), Mucor spp. (1) and Fusarium spp. (1). In the drug sensitivity assay, instances of resistance included: Partial sensitivity of Aspergillus fumigatus to Itraconazole (1), Partial sensitivity of Aspergillus niger to Ketoconazole (1), and Resistance of Aspergillus niger to Itraconazole (1). Conclusion: The pattern of nosocomial fungal infection with pathogenic fungi and the drug susceptibility pattern of these organisms in other regions of Iran and the world is relatively consistent with the present study results. And drugs listed in global guidelines for treating these infections, such as voriconazole and caspofungin in the treatment of invasive aspergillosis and amphotericin B in the treatment of invasive mucormycosis and Fusarium wilt, are now effective drugs. Keywords: Invasive fungal infections, Airborne fungi, Dru

Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.

Invasive pulmonary aspergillosis in COVID-19 patients

A retrospective analysis of the medical data of 12 patients with COVID-19 was performed. For the diagnosis of invasive aspergillosis the international criteria ECMM/ISHAM 2020 were used. We analyzed the scientific literature data on the diagnosis and treatment of invasive aspergillosis in patients with COVID-19.Results. Among the 12 examined patients with a severe course of COVID-19, invasive aspergillosis was diagnosed in 5 patients. Four patients (80%) were treated in the ICU. Steroids or interleukin-6 inhibitors were used in 80% patients. Severe lymphocytopenia was in 80% patients, neutropenia 20%. A fever refractory to antibiotic therapy was noted in 80% patients, an increase in respiratory failure – 60%, acute respiratory distress syndrome – 60%. All patients showed negative dynamics of changes in the chest CT scan. Invasive aspergillosis was confirmed with a positive test for galactomannan in bronchoalveolar lavage and / or serum in 100% of cases. All patients received antifungal therapy with voriconazole and/or caspofungin. The overall 12-week survival rate was 80%.Conclusion. In ICU patients with severe COVID-19 and progressive pulmonary symptoms invasive aspergillosis should be excluded. Examination of substrates from the lower respiratory tract (BAL, tracheal aspirate, or nonbronchoscopic lavage) is necessary. Laboratory examination should include microscopy, culture and test for galactomannan. Voriconazole and isavuconazole are drugs of choice for the treatment of invasive aspergillosis in patients with COVID-19.