Invasive Mediastinal Aspergillosis in an 18-Year-Old Immunocompetent Female Leading to Stroke.

We present a case of invasive pulmonary aspergillosis in an immunocompetent young female. An 18-year-old female presented with symptoms of a left-sided middle cerebral artery (MCA) stroke with right arm weakness and aphasia. Computed tomography (CT) brain confirmed the diagnosis of stroke. Further history revealed that the patient had been experiencing low-grade fevers with occasional shortness of breath for the past year. The blood work had eosinophilia at that time for which she was given mebendazole but saw little improvement. Chest X-rays showed upper lobe consolidation for which a tuberculosis (TB) workup was also done, which also came out negative. At the current presentation, she underwent further workup with echocardiography and eventual ultrasound-guided mediastinal biopsy that ultimately led to the correct diagnosis of aspergillosis. However, sadly, it was already too late for the patient who passed away one day after the commencement of the amphotericin B therapy. This paper hopes to decrease the threshold of clinical suspicion for invasive aspergillosis (IA) regardless of the immunity status of the patient, especially if they are presenting with an unrelenting mediastinal or pulmonary symptom complex in the setting of eosinophilia.

Long-read sequencing and de novo genome assembly data of Candida parapsilosis HMC1 and Rhodotorula mucilaginosa LBMH1012, two novel isolates with antifungal resistance signatures.

Candida parapsilosis and Rhodotorula mucilaginosa are opportunistic pathogens affecting mostly immunocompromised hosts. Both species have emerged as causes of invasive candidiasis and sepsis respectively. Here we present high-quality long-read genome assemblies for a strain of C. parapsilosis isolated from human breast milk, with multiple predicted signatures consistent with Candida Drug Resistance CDR1/CDR2 and Multi Drug Resistance MDR1-type genes, also for an environmental strain of R. mucilaginosa with multiresistance to azole antifungals. The genome sequencing was performed using the R9.4.1 flowcell with the MinION Mk1B sequencer (Oxford Nanopore Technologies, Oxford, UK). The draft genome of C. parapsilosis HMC1 was assembled from 85,745 long-reads and has 13,114,208 bp in length and comprises 10 contigs making it a highly contiguous assembly. The R. mucilaginosa LBMH1012 assembly has 23,636,156 bp in length and comprises 54 contigs. The genome completeness was estimated as 94.02 % and 91.40 % respectively using BUSCO. These data may be useful to explore the genetic diversity landscape in both species, infer potential causal genes for antifungal resistance and virulence, and represent an addition to the useful sequence space on emerging fungal pathogens.

ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit.

Rationale: Invasive fungal infections (IFI) in the intensive care unit (ICU) are an emerging problem owing to the use of broad-spectrum antibiotics, immunosuppressive agents, and frequency of indwelling catheters. Timely diagnosis which is imperative to improve outcomes can be challenging. This position statement is aimed at understanding risk factors, providing a rational diagnostic approach, and guiding clinicians to optimize antifungal therapy. Objectives: To update evidence on epidemiology, risk factors, diagnostic approach, antifungal initiation strategy, therapeutic interventions including site-specific infections and role of therapeutic drug monitoring in IFI in ICU and focus on some practice points relevant to these domains. Methodology: A committee comprising critical care specialists across the country was formed and specific aspects of fungal infections and antifungal treatment were assigned to each member. They extensively reviewed the literature including the electronic databases and the international guidelines and cross-references. The information was shared and discussed over several meetings and position statements were framed to ensure their reliability and relevance in critical practice. The draft document was prepared after obtaining inputs and consensus from all the members and was reviewed by an expert in this field. Results: The existing evidence on the management of IFI was updated and practice points were prepared under each subheading to enable critical care practitioners to streamline diagnosis and treatment strategies for patients in the ICU with additional detail on site-specific infections therapeutic drug monitoring. Conclusion: This position statement attempts to address the management of IFI in immunocompetent and non-neutropenic ICU patients. The practice points should guide in optimization of the management of critically ill patients with suspected or proven fungal infections. How to cite this article: Bhattacharya PK, Chakrabarti A, Sinha S, Pande R, Gupta S, Kumar AAK, et al. ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S20-S41.

Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study.

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.

Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

In vitro small molecule screening to inform novel candidates for use in fluconazole combination therapy in vivo against Coccidioides.

Identifying improved treatments for severe and refractory coccidioidomycosis (Valley fever) is needed. This endemic fungal disease is common in North and South America, and cases have increased substantially over the last 30 years. The current standard of care, oral daily fluconazole, often fails to completely eradicate Coccidioides infection; however, the high cost of identifying new compounds effective in treating Valley fever is a barrier to improving treatment. Therefore, repurposing existing pharmaceutical agents in combination with fluconazole therapy is an attractive option. We screened the Library of Pharmacologically Active Compounds (LOPAC) small molecule library for compounds that inhibited fungal growth in vitro and determined IC50 values for a subset of compounds. Based on these findings, we tested a small subset of these agents to validate the screen, as well as to test the performance of fluconazole in a combination therapy approach, as compared with fluconazole alone, in a murine model. We observed that combination therapy of tamoxifen:fluconazole and sertraline:fluconazole significantly reduced the burden of live fungus in the lung compared with fluconazole alone, and we observed reduced or nonexistent dissemination. These results suggest that tamoxifen and sertraline may be repurposed as adjunctive agents in the treatment of this important fungal disease. IMPORTANCE: Developing new drugs, especially for regional orphan diseases, such as Valley Fever, is a slow and costly endeavor. However, there is a wealth of FDA-approved drugs available for repurposing, offering a more economical and expedited approach to improve treatment. Those existing compounds with antifungal properties can become novel therapies with relative ease: a considerable advantage for patients in need of alternative treatment. Despite the scope of remaining tasks, our comprehensive screening of potential candidates has revealed promising combinations for further exploration. This effort outlines a practical pipeline for Valley fever drug screening and identifies viable drug combinations that could impact patients more rapidly than single drug development pathways.

Revision of antifungal strategies definitions for invasive fungal infections (proven/probable/possible) in 461 patients with haematological malignancies (REDEFI-SEIFEM).

BACKGROUND: Invasive fungal infections (IFI) are a relevant cause of morbidity and mortality among patients with haematological neoplasms (HMs). Since 2002, a classification of IFI based on host factors, clinical and radiological features and mycological tests was published for research purpose. OBJECTIVES: These criteria are widely used in clinical practice to identify patients at risk for IFI. The aim of the study was to evaluate the clinical applicability of EORTC/MSG 2008 criteria for the diagnosis of IFI in daily practice. PATIENTS/METHODS: This multicentre, non-interventional, observational, prospective study gathered all consecutive inpatients with HMs in which an intravenous antifungal treatment was started. Exclusion criteria were a previous or concomitant transplant procedure, outpatient status and oral antifungal therapy. EORTC/MSG 2008 criteria were used to classify patients at the beginning of antifungal therapy and at 30 days. An independent board reviewed the classification of IFI given by local clinicians at T0 and T30. RESULTS: The highest percentage of agreement was found for possible IFI (96%), while a lower agreement was reported for proven IFI (74%), and the highest variability was observed for probable IFI (56%). At T30, the board re-evaluation confirmed a strict agreement for possible IFI only (98%). Among 306 patients classified as possible, 156 (51%) patients showed non-typical radiological findings and 45 (15%) patients presented host factors only. CONCLUSIONS: In real life, the EORTC/MSG criteria can be applicable only for possible IFI. As non-typical radiological findings are reported in possible IFI, introducing a new IFI category should be considered.

Inhibition of Development and Metabolism of Dual-Species Biofilms of Candida albicans and Candida krusei (Pichia kudriavzevii) by Organoselenium Compounds.

Although Candida albicans is the most frequently identified Candida species in clinical settings, a significant number of infections related to the non-albicans Candida (NAC) species, Candida krusei, has been reported. Both species are able to produce biofilms and have been an important resistance-related factor to antimicrobial resistance. In addition, the microbial relationship is common in the human body, contributing to the formation of polymicrobial biofilms. Considering the great number of reports showing the increase in cases of resistance to the available antifungal drugs, the development of new and effective antifungal agents is critical. The inhibitory effect of Organoselenium Compounds (OCs) on the development of Candida albicans and Candida krusei was recently demonstrated, supporting the potential of these compounds as efficient antifungal drugs. In addition, OCs were able to reduce the viability and the development of biofilms, a very important step in colonization and infection caused by fungi. Thus, the objective of this study was to investigate the effect of the Organoselenium Compounds (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2 on the development of dual-species biofilms of Candida albicans and Candida krusei produced using either RPMI-1640 or Sabouraud Dextrose Broth (SDB) media. The development of dual-species biofilms was evaluated by the determination of both metabolic activity, using a metabolic assay based on the reduction of XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and identification of either Candida albicans and Candida krusei on CHROMagar Candida medium. Biofilm formation using RPMI-1640 was inhibited in 90, 55, and 20% by 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. However, biofilms produced using SDB presented an inhibition of 62, 30 and 15% in the presence of 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. The metabolic activity of 24 h biofilms was inhibited by 35, 30 and 20% by 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively, with RPMI-1640; however, 24 h biofilms formed using SDB were not modified by the OCs. In addition, a great reduction in the number of CFUs of Candida albicans (93%) in biofilms produced using RPMI-1640 in the presence of 30 µM (p-MeOPhSe)2 was observed. However, biofilms formed using SDB and treated with 30 µM (p-MeOPhSe)2 presented a reduction of 97 and 69% in the number of CFUs of Candida albicans and Candida krusei, respectively. These results demonstrated that Organoselenium Compounds, mainly (p-MeOPhSe)2, are able to decrease the metabolic activity of dual-species biofilms by reducing both Candida albicans and Candida krusei cell number during biofilm formation using either RPMI-1640 or SDB. Taken together, these results demonstrated the potential of the OCs to inhibit the development of dual-species biofilms of Candida albicans and Candida krusei.

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

This article summarizes the epidemiology and risk factors for IFD, before focusing on the effectiveness and safety of the antifungal agent isavuconazole for treatment of invasive aspergillosis and mucormycosis, and its potential to prevent IFD in specific patient populations.

An update on pharmacotherapy for fungal infections in allogeneic stem cell transplant recipients.

INTRODUCTION: Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. AREAS COVERED: We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024. EXPERT OPINION: The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is Candida spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

Therapy of traditional Chinese medicine in Candida spp. and Candida associated infections: A comprehensive review.

Candida spp. are commonly a group of opportunistic dimorphic fungi, frequently causing diverse fungal infections in immunocompromised or immunosuppressant patients from mucosal disturbs (oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated infections (systemic candidiasis) with high morbidity and mortality. Importantly, several Candida species can be isolated from diseased individuals with digestive, neuropathic, respiratory, metabolic and autoimmune diseases. Due to increased resistance to conventional antifungal agents, the arsenal for antifungal purpose is in urgent need. Traditional Chinese Medicines (TCMs) are a huge treasury that can be used as promising candidates for antimycotic applications. In this review, we make a short survey of microbiological (morphology and virulence) and pathological (candidiasis and Candida related infections) features of and host immune response (innate and adaptive immunity) to Candida spp.. Based on the chemical structures and well-studied antifungal mechanisms, the monomers, extracts, decoctions, essential oils and other preparations of TCMs that are reported to have fair antifungal activities or immunomodulatory effects for anticandidal purpose are comprehensively reviewed. We also emphasize the importance of combination and drug pair of TCMs as useful anticandidal strategies, as well as network pharmacology and molecular docking as beneficial complements to current experimental approaches. This review construct a therapeutic module that can be helpful to guide in-future experimental and preclinical studies in the combat against fungal threats aroused by C. albicans and non-albicans Candida species.

Case Commentary: Extending our therapeutic range against multidrug-resistant Candida.

Deep-seated Candida spp. infections may necessitate extended durations of antifungal therapy. Increasing resistance to first-line antifungals threatens the most common options for long-term treatment. In this issue, Ponta et al. (Antimicrob Agents Chemother 68:e00750-24, 2024, https://doi.org/10.1128/aac.00750-24) present cases in which they used rezafungin, a novel long-acting echinocandin antifungal, for extended durations. While excellent clinical evidence supports the short-term safety of rezafungin, these cases demonstrate that rezafungin may additionally have a role in long-term suppressive therapy for antifungal-resistant Candida spp. infections.

Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.

Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.

First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors.

Aspergillus fungi constitute a pivotal element within ecosystems, serving as both contributors of biologically active compounds and harboring the potential to cause various diseases across living organisms. The organism's proteolytic enzyme complex, termed the degradome, acts as an intermediary in its dynamic interaction with the surrounding environment. Using techniques such as genome and transcriptome sequencing, alongside protein prediction methodologies, we identified putative extracellular peptidases within Aspergillus ochraceus VKM-F4104D. Following manual annotation procedures, a total of 11 aspartic, 2 cysteine, 2 glutamic, 21 serine, 1 threonine, and 21 metallopeptidases were attributed to the extracellular degradome of A. ochraceus VKM-F4104D. Among them are enzymes with promising applications in biotechnology, potential targets and agents for antifungal therapy, and microbial antagonism factors. Thus, additional functionalities of the extracellular degradome, extending beyond mere protein substrate digestion for nutritional purposes, were demonstrated.

Bisphosphonates synergistically enhance the antifungal activity of azoles in dermatophytes and other pathogenic molds.

Superficial infections of the skin, hair, and nails by fungal dermatophytes are the most prevalent of human mycoses, and many infections are refractory to treatment. As current treatment options are limited, recent research has explored drug synergy with azoles for dermatophytoses. Bisphosphonates, which are approved to treat osteoporosis, can synergistically enhance the activity of azoles in diverse yeast pathogens but their activity has not been explored in dermatophytes or other molds. Market bisphosphonates risedronate, alendronate, and zoledronate (ZOL) were evaluated for antifungal efficacy and synergy with three azole antifungals: fluconazole (FLC), itraconazole (ITR), and ketoconazole (KET). ZOL was the most active bisphosphonate tested, displaying moderate activity against nine dermatophyte species (MIC range 64-256 µg/mL), and was synergistic with KET in eight of these species. ZOL was also able to synergistically improve the anti-biofilm activity of KET and combining KET and ZOL prevented the development of antifungal resistance. Rescue assays in Trichophyton rubrum revealed that the inhibitory effects of ZOL alone and in combination with KET were due to the inhibition of squalene synthesis. Fluorescence microscopy using membrane- and ROS-sensitive probes demonstrated that ZOL and KET:ZOL compromised membrane structure and induced oxidative stress. Antifungal activity and synergy between bisphosphonates and azoles were also observed in other clinically relevant molds, including species of Aspergillus and Mucor. These findings indicate that repurposing bisphosphonates as antifungals is a promising strategy for revitalising certain azoles as topical antifungals, and that this combination could be fast-tracked for investigation in clinical trials. IMPORTANCE: Fungal infections of the skin, hair, and nails, generally grouped together as "tineas" are the most prevalent infectious diseases globally. These infections, caused by fungal species known as dermatophytes, are generally superficial, but can in some cases become aggressive. They are also notoriously difficult to resolve, with few effective treatments and rising levels of drug resistance. Here, we report a potential new treatment that combines azole antifungals with bisphosphonates. Bisphosphonates are approved for the treatment of low bone density diseases, and in fungi they inhibit the biosynthesis of the cell membrane, which is also the target of azoles. Combinations were synergistic across the dermatophyte species and prevented the development of resistance. We extended the study to molds that cause invasive disease, finding synergy in some problematic species. We suggest bisphosphonates could be repurposed as synergents for tinea treatment, and that this combination could be fast-tracked for use in clinical therapy.

Median Rhomboid Glossitis: A Case Study.

A smooth, red, oval, or rhomboid patch on the dorsal midline is the classic presentation of median rhomboid glossitis (MRG), a rare and benign lesion of the tongue. MRG is still not fully understood, which presents diagnostic hurdles and calls for additional clinical investigation. It is frequently associated with candidal infections. We describe a case of a 42-year-old man who initially appeared to have either mechanical irritation or thermal injury related to a painless patch on the dorsum surface of the tongue. We document a case of MRG that was consulted for a standard dental examination in this case report. This article also highlights a dentist's need to identify the lesion and provide appropriate education for the patient.

Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study.

BACKGROUND: Current guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery. METHODS: A retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France. Patients treated with early empirical antifungals for HC-IAI after abdominal surgery were compared with controls who did not receive such antifungals. The primary endpoint was the death rate at 90 days, and the secondary endpoints were the death rate at 1 year and composite criteria evaluated at 30 days following the HC-IAI diagnosis, including the need for re-intervention, inappropriate antimicrobial therapy and death, whichever occurred first. RESULTS: At 90 days, the death rate was significantly decreased in the patients treated with empirical antifungals compared with the control group (11.4% and 20.7%, respectively, p = 0.02). No differences were reported for the secondary outcomes. CONCLUSION: The use of early empirical antifungal therapy was associated with a decreased death rate at 90 days, with no effect on the death rate at 1 year, the death rate at 30 days, the rate of re-intervention, the need for drainage, and empirical antibiotic and antifungal therapy failure at 30 days.

Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris.

Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials.

Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis.

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that is prevalent in tropical countries, particularly in developing regions of Asia and Africa. Factors like corneal lens misuse, inappropriate steroid use, and diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, and ocular deformities. Accurate pathological diagnosis is crucial for effective therapeutic intervention. Topical antifungal therapy with surface healing medications proves effective in preventing fungal-borne ulcers. Managing FK requires a comprehensive understanding of fungal pathogenesis, guiding formulation strategies and preventive measures to curb global ocular blindness. This review provides in-depth insights into FK, covering etiology, epidemiology, pathogenesis, therapeutic interventions, antifungal resistance, limitations, prevention, and future perspectives on ocular surface disease management.

Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.