Management Of Invasive Fungal Infections Research Articles

P-160. Exploring Invasive Fungal Infection Diagnosis and Treatment: A Cross-Continental Comparison between Brazil and Europe

Abstract Background Brazil's tropical climate and a higher prevalence of immunocompromised cases due to conditions like HIV/AIDS contribute to an increased incidence of invasive fungal infections (IFIs) like histoplasmosis and paracoccidioidomycosis. In Europe, vulnerable populations undergoing immunosuppressive therapies or organ transplants face elevated risks of IFIs such as candidiasis and aspergillosis. Methods An online survey, conducted to assess diagnostic capacities for IFIs, engaged mycologists across Europe and Brazil. The survey encompassed various aspects, including institutional characteristics, perspectives on IFIs, and the utilization of diagnostic techniques such as microscopy, culture, serology, molecular testing, and therapeutic drug monitoring. Results As of 2023, the survey encompassed 484 centers, with 96 in Brazil and 388 in Europe. In Brazil, 45% of centers had on-site mycological diagnostics, while in Europe, this figure was higher at 58% (p< 0.001). Breaking down diagnostic test availability in Brazil: microscopy was accessible in 96% of centers, culture in 95%, antigen detection in 63%, antibody detection in 47%, and molecular tests in 19%. In contrast, in Europe, the distribution was: culture in 99% of centers, microscopy in 97%, antigen detection in 94%, molecular tests in 85%, and antibody detection in 82%. Significant statistical disparities were observed in antigen detection, molecular tests, and antibody detection (p< 0.001). Concerning antifungal treatment in Brazil, at least one formulation of amphotericin B was used in 72% of centers, at least one echinocandin in 55%, fluconazole in 93%, and the primary mould-active azole, itraconazole, in 66%. In Europe, at least one formulation of amphotericin B was used in 87% of centers, at least one echinocandin in 89%, fluconazole in 93%, and the main mould-active azole, itraconazole, in 89%. A notable difference was observed in access to all antifungals (p< 0.001). Conclusion Brazil's healthcare disparities and limited access to advanced care impact the diagnosis and management of IFIs, while Europe's widely-established healthcare infrastructure facilitates early detection and treatment. A call to action for the improvement of capabilities in Brazil is warranted. Disclosures Oliver A. Cornely, Prof. Dr., Abbott: Honoraria|Abbvie: Advisor/Consultant|Abbvie: Honoraria|AiCuris: Advisor/Consultant|Akademie fur Infektionmedizin: Honoraria|Al-Jazeera Pharmaceuticals/Hikma: Honoraria|amedes: Honoraria|AstraZeneca: Honoraria|Basilea: Advisor/Consultant|Biocon: Advisor/Consultant|BMBF: Grant/Research Support|Boston Strategic Partners: Advisor/Consultant|CIdara: Advisor/Consultant|CIdara: Expert Testimony|CIdara: Grant/Research Support|CIdara: Participation on a DRC or DSMB|CoRe Consulting: Stocks/Bonds (Private Company)|Deutscher Arzteverlag: Honoraria|DZIF: Grant/Research Support|EasyRadiology: Stocks/Bonds (Private Company)|EU-DG RTD: Grant/Research Support|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Grupo Biotoscana/United Medical/Knight: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|IQVIA: Advisor/Consultant|IQVIA: Participation on a DRC or DSMB|Janssen: Advisor/Consultant|Janssen: Participation on a DRC or DSMB|Matinas: Advisor/Consultant|MedPace: Advisor/Consultant|MedPace: Grant/Research Support|MedPace: Participation on a DRC or DSMB|Medscape/WebMD: Honoraria|MedUpdate: Honoraria|Menarini: Advisor/Consultant|Moderna: Honoraria|Molecular Partners: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|MSG-ERC: Advisor/Consultant|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Noscendo: Honoraria|Noxxon: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Grant/Research Support|Pardes: Advisor/Consultant|Partner Therapeutics: Advisor/Consultant|Patent: US18/562644|Paul-Martini-Stiftung: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|PSI: Advisor/Consultant|PSI: Participation on a DRC or DSMB|Pulmocide: Participation on a DRC or DSMB|Sandoz: Honoraria|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Seqirus: Advisor/Consultant|Seqirus: Honoraria|Seres: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria|streamedup!: Honoraria|The Prime Meridian Group: Advisor/Consultant|Touch Independent: Honoraria|Vitis: Honoraria

Isolated fungal liver abscess in pediatric acute lymphoblastic leukemia – A case report

Diagnosis and management of invasive fungal infections pose a challenge to the treating physician in patients with hematological malignancies. The incidence is lesser in acute lymphoblastic leukemia (ALL), compared to the other hematological malignancies. The diagnosis is often delayed due to the non-specific clinical findings and negative cultures. Here, we report a case of B-cell ALL, on chemotherapy, diagnosed to have hepatic fungal abscess caused by Aspergillus fumigatus species. Interestingly, the patient did not have neither neutropenia nor any other systemic involvement of fungal infection at presentation. The case was successfully managed with percutaneous drainage and systemic antifungal therapy using voriconazole. Timely intervention helped in the diagnosis and proper management of the case, thus preventing a disseminated invasive fungal infection.

Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital.

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ± 15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9-8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up.

Strengthening Fungal Infection Diagnosis and Treatment: An In-depth Analysis of Capabilities in Honduras.

Invasive fungal infections (IFIs) are a major public health concern in low- and middle-income countries (LMICs) due to limited diagnostic and treatment resources, leading to high morbidity and mortality. Despite their significant global burden, IFIs are underrecognized and underdiagnosed in LMICs. This study evaluates the diagnostic and therapeutic capacities for managing IFI in Honduras, a country with unique health care challenges. From March to December 2023, a comprehensive survey was conducted across multiple health care centers in Honduras. The survey, reviewed for content and clarity by local medical institutions, targeted medical microbiologists and clinicians to assess various aspects of fungal disease diagnosis and treatment. Data included the availability and use of diagnostic tools and antifungal therapies, identifying gaps and limitations in current practices. The survey revealed that Candida spp (97.4%) and Aspergillus spp (35.9%) were the most concerning pathogens. Although microscopy and culture methods were available in most institutions, their application in suspected IFI cases was inconsistent, and antifungal susceptibility testing was rarely performed. Advanced diagnostic techniques, such as antigen detection, were available in only a few institutions, while antibody detection and polymerase chain reaction testing were entirely absent. All hospitals had access to at least 1 triazole antifungal, typically fluconazole, but there was a notable scarcity of more potent antifungals, including amphotericin B formulations and echinocandins. The limited use of available diagnostic tools and the restricted availability of essential antifungals were identified as major barriers to effective IFI management. This study highlights significant gaps in the diagnostic and therapeutic capabilities for managing IFI in Honduras. The underutilization of basic diagnostic tools, the inaccessibility of advanced testing methods, and the limited availability of essential antifungal medications underscore the urgent need for capacity-building initiatives, infrastructure improvements, and policy reforms. Addressing these deficiencies is critical for enhancing the management of IFI in Honduras, with broader implications for similar LMIC settings. These findings can inform targeted interventions and resource allocation to improve outcomes for patients with IFI.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

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

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. 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. 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. 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. 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. 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.

Promoting antifungal stewardship through an antifungal multidisciplinary team in a paediatric and adult tertiary centre in the UK.

Invasive fungal infections (IFIs) present significant challenges, especially among immunocompromised patients, with associated high morbidity, mortality and significant economic impact. Diagnostic difficulties and the emergence of antifungal resistance necessitates enhanced antifungal stewardship (AFS) efforts. We report outcomes from a review of our multidisciplinary approach to AFS, based in a 1300-bed teaching hospital in the South-West of England. Retrospectively reviewing all adult and paediatric cases over 12 months in 2022, we investigated demographics, diagnosis, antifungal therapy and adherence to AFS advice, including clinical, mycological, financial and teamwork metrics. Data were extracted from our AFS database, supported by pharmacy records. The AFS multidisciplinary team (MDT) reviewed 111 patients, with 30 day and 1 year mortality of 22.7% and 35.4%, respectively. IFIs classified as proven accounted for 26%, with fungal pathogens identified in 36.3% of cases. Antifungal consumption (by 25.1%) and expenditure (by 59.9%) decreased from 2018 to 2022. The AFS MDT issued 324 recommendations, with a 93% acceptance rate. Our approach to AFS, centred around a weekly MDT, demonstrated improvements in IFI management, antifungal consumption and cost-efficiency. This single-centre study highlights the value of a comprehensive, collaborative approach to AFS involving experts in mycology, infection, radiology, antifungal therapies and clinical teams. The programme's success in paediatric and adult populations and the near-universal acceptance of its recommendations show its potential as a model for replication. It represents a model for enhancing patient care and AFS practices, with future directions aimed at expanding service reach and the integration of further rapid diagnostic modalities.

Hope on the Horizon? Aptamers in Diagnosis of Invasive Fungal Infections.

Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due to their stability, ease of production, and specificity to signature molecules of fungal pathogens, short single-stranded sequences of DNA, RNA, and XNA, collectively called aptamers, have emerged as promising diagnostic markers. In this perspective, we summarize recent progress in aptamer-based diagnostic tools for IFIs and discuss how these tools could potentially meet the needs and provide economical and simple solutions for point-of-care for better management of IFIs.

A review of the epidemiology of invasive fungal infections in Asian patients with hematological malignancies (2011-2021).

The incidence of invasive fungal infection (IFI) is increasing, especially among patients diagnosed with hematological malignancies due to their immunocompromised nature. Other risk factors include advanced age, exposure to immunosuppressants, neutropenia, and catheter use. Some of the most common IFI organisms reported are Candida and Aspergillus species, and other fungal species, including Scedosporium, Trichosporon, Cryptococcus, and Fusarium have also increasingly been reported in the past years. However, the epidemiologic data on IFI among patients with hematological malignancies in Asian countries are lacking. Therefore, we investigated published epidemiologic data on such cases from the past 10 years (2011-2021) and discuss the challenges faced in the diagnosis and management of IFIs in Asia.

Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix.

Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY-078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once-weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off-label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit

BackgroundThe global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species.Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed.MethodsUsing a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%.ResultsA total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). ConclusionThe results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

Enhancing antifungal and biocompatible efficacy of undecanoic acid through incorporation with chitosan-based nanoemulsion

The management of invasive fungal infections in humans poses significant challenges due to the intricate nature of the treatment, which is both arduous and costly, necessitating routine diagnostic procedures. Consequently, this investigation aimed to formulate a chitosan-based nanoemulsion (CS NEMs) incorporating the antifungal agent undecanoic acid (UDA), characterizing these NEMs and assessing their antifungal efficacy against both filamentous and non-filamentous fungal pathogens. The CS-based UDA NEMs were synthesized by introducing the surfactant Triton X-100 and the stabilizer glycerol. Nanoparticle tracking analysis (NTA) and SEM demonstrated the CS-UDA NEMs with an average size of 145 nm and 164.5 ± 24 nm, respectively. The successful formation of CS-UDA NEMs was verified through FTIR and XRD. CS-UDA NEMs exhibited exceptional inhibition against Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Candida albicans with MFC of 500, 500, 250 and 250 μg/mL, respectively. Additionally, CS-UDA NEMs displayed comparatively lower antioxidant activity as determined by DPPH and ABTS radical scavenging assays. Importantly, CS-UDA NEMs demonstrated no cytotoxic effects on NIH3T3 cells even at higher concentration (1000 μg/mL), as confirmed by cell viability and fluorescent staining assays. In conclusion, this study suggests that the developed CS-UDA NEMs hold promise as potent antifungal agents with diverse potential applications.

Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Usefulness of 18F‐FDG PET‐CT for the management of invasive fungal infections: A retrospective cohort from a tertiary university hospital

AbstractBackground18F‐FDG PET‐CT is a potentially useful technique to help manage invasive fungal infection (IFI), but information on this topic is scarce.ObjectivesTo describe our experience using 18F‐FDG PET‐CT for IFI management.Patients/MethodsRetrospective cohort of IFI episodes in a university hospital from 2018 to 2023 with a18F‐FDG PET‐CT performed during the episode. We analysed its impact on IFI management compared to conventional imaging.ResultsThirty‐five patients diagnosed with 36 episodes of IFI (52.8% moulds, 44.4% yeasts and 2.8% Pneumocystis) underwent 55 18F‐FDG PET‐CT. 74.3% were immunocompromised, including 45.7% solid organ transplant recipients. Indications for 18F‐FDG PET‐CT were diagnostic (10.9%), staging (47.3%) and follow‐up (41.8%). Altogether 18F‐FDG PET‐CT added value to IFI management in 50.9% episodes. In 26 patients who had both staging 18F‐FDG PET‐CT and conventional imaging, sites of IFI dissemination were detected in 53.8% and 19.2%, respectively. Staging 18F‐FDG PET‐CT unveiled occult sites in 34.6%, uncovering unknown dissemination in 19.2%. In the evaluation of endocarditis in patients with fungemia, it contributed in at least 38.5%.Follow‐up 18F‐FDG PET‐CTs had an added value in 47.8% episodes. They were allowed to de‐escalate antifungal therapy in 26.1%. There were discordant findings between 18F‐FDG PET‐CT and CT follow‐up in 40% cases.ConclusionsOverall, 18F‐FDG PET‐CT added value to IFI management in more than 50% of the episodes. It increased the diagnosis of occult sites, unveiled disseminated disease missed out by conventional imaging, and contributed to diagnose or rule out endocarditis in fungemia. Follow‐up 18F‐FDG PET‐CT helped adjust the treatment duration and deserves further study.

Challenges in management of invasive fungal infections in stem cell transplant.

Invasive fungal infections cause significant morbidity and mortality in hematopoietic stem cell transplant recipients. In order to minimize these infections, prophylaxis has become routine, although the agents used have changed over time. This presents new challenges as we consider an approach to breakthrough infections and recognize the epidemiologic shift toward isolates with higher rates of drug resistance. This review outlines the management of the most common pathogens (Candida, Aspergillus, Mucorales) as well as rarer pathogens that have higher rates of resistance (Trichosporon, Fusarium, Scedosporium, and Lomentospora). We discuss potential approaches to proven or possible breakthrough infections with yeast and pulmonary mold disease. Finally, we outline the role for combination therapy and newer antifungals, acknowledging current knowledge gaps and areas for future exploration.

Invasive fungal infections in liver diseases.

Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.

Diagnosis, Prognostic Factors and Therapeutic Management of Invasive Fungal Infections. The Results of a Cross-Sectional Study in a Tunisian Hospital

Introduction: Invasive fungal infection (IFI) is associated to a high morbidity, mortality and healthcare costs. Patients and Methods: Our cross-sectional study focuses on patients who developed an IFI and treated with systemic antifungals, over a period of 14 months in a tunisian hospital. Clinico-biological data, risk factors, and therapeutic management were collected and analyzed. Results and Discussion: We report 51 cases with IFI, aged between 15 and 85 years. 56.9% were hospitalized in intensive care units and nearly 80% already suffer from other pathologies. Based on the EORTC/MSGERC criteria and clinical, radiological and biological data, IFIs were classified as follows : 49.3% cases of “proven infection”, 10.1% cases of “probable infection” and 17.4% cases of “possible infection”. Two risk factors revealed to correlate with a poor prognosis: intubation or invasive ventilation and long-term corticosteroid therapy. C.glabrata was the most common isolated species, agent responsible for invasive candidiasis. Resistances for fluconazole were not noticed. The anti-fungals prescribed for management of the IFI were: caspofungin, anidulafungin, voriconazole, amphotericin B and fluconzaole (following de-escalation). Conclusion: A close multidisciplinary collaboration between clinicians, radiologists, mycologists and pharmacists can improve the prognosis of these infections.

Challenges in the Management of Invasive Fungal Infections in the Middle East: Expert Opinion to Optimize Management Using a Multidisciplinary Approach.

Invasive fungal infection (IFI) is a significant global healthcare concern among critically ill and immunocompromised patients. In Middle Eastern countries, IFI has been steadily increasing among hospitalized patients in the past two decades. Diagnosis of IFI at an early stage is crucial for efficient management. Invasive fungal infection management is complex and requires the involvement of physicians from different specialties. There are several challenges associated with IFI management in the countries in the Middle East. This review aims to understand the key challenges associated with IFI management in the Middle East, encompassing epidemiology, diagnosis, therapeutic options, and optimizing a multidisciplinary approach. In addition, this review aims to incorporate expert opinions from multidisciplinary fields for optimizing IFI management in different Middle Eastern countries by addressing key decision points throughout the patient's journey. Lack of epidemiological data on fungal infections, slow and poorly sensitive conventional culture-based diagnostic tests, limited availability of biomarker testing, lack of awareness of clinical symptoms of the disease, limited knowledge on fungal infections, lack of local practice guidelines, and complicated disease management are the major challenges associated with IFI diagnosis and management in the Middle Eastern countries. Implementation of a multidisciplinary approach, antifungal stewardship, improved knowledge of fungal infections, the use of rapid diagnostic tests, and enhanced epidemiological research are warranted to lower the IFI burden in the Middle East.

The Argentinian landscape of mycological diagnostic capacity and treatment accessibility.

Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.

Determining the usefulness of systematic 18F-FDG PET/CT for the management of invasive fungal infection (PETIFI project): a prospective national multicentre cohort study protocol

IntroductionThe evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission...