Cases Of Invasive Fungal Infections Research Articles

Humans vs. Fungi: An Overview of Fungal Pathogens against Humans.

Human fungal diseases are infections caused by any fungus that invades human tissues, causing superficial, subcutaneous, or systemic diseases. Fungal infections that enter various human tissues and organs pose a significant threat to millions of individuals with weakened immune systems globally. Over recent decades, the reported cases of invasive fungal infections have increased substantially and research progress in this field has also been rapidly boosted. This review provides a comprehensive list of human fungal pathogens extracted from over 850 recent case reports, and a summary of the relevant disease conditions and their origins. Details of 281 human fungal pathogens belonging to 12 classes and 104 genera in the divisions ascomycota, basidiomycota, entomophthoromycota, and mucoromycota are listed. Among these, Aspergillus stands out as the genus with the greatest potential of infecting humans, comprising 16 species known to infect humans. Additionally, three other genera, Curvularia, Exophiala, and Trichophyton, are recognized as significant genera, each comprising 10 or more known human pathogenic species. A phylogenetic analysis based on partial sequences of the 28S nrRNA gene (LSU) of human fungal pathogens was performed to show their phylogenetic relationships and clarify their taxonomies. In addition, this review summarizes the recent advancements in fungal disease diagnosis and therapeutics.

Invasive Fungal Infections Among Patients with Hematological Malignancies: A Two-Year Multicentric Study from Tehran, Iran

Background: Invasive fungal infection (IFI) is a life-threatening condition, particularly in individuals with compromised immune systems. Objectives: Our study aims to evaluate IFI in hospitalized patients with hematological malignancies. Methods: In this retrospective cross-sectional study, we evaluated patients with hematological malignancies admitted to two university hospitals in Tehran, Iran, from 2020 to 2021 for IFI. We selected only those patients who had been hospitalized for at least four days for antimicrobial treatment. Data analysis was conducted using SPSS-26 software, employing Mann-Whitney U, chi-square, and Fisher exact tests. Results: During the study period, 60 out of 213 patients with hematological malignancies were admitted for antimicrobial treatment. The average age of the patients was 57.1 years, with fever being the most common symptom, reported in 63.3% of cases. We identified 24 cases of IFI, including three proven cases (Candida spp.) and 21 probable cases. Statistical analysis showed a lower mean neutrophil count in the IFI group compared to the non-IFI group (3862 versus 12881, P = 0.001) and a higher mortality rate (58.3% versus 27.8%, P = 0.031). Conclusions: Our study revealed that severe neutropenia is a significant risk factor for IFI, and the mortality rate associated with IFI remains high despite advances in the treatment of hematological malignancies.

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.

Rare Invasive Fungal Infections in Hematologic Patients: A Large Unicentric Series

Introduction: Invasive fungal infections (IFI) are a major cause of infectious mortality in immunocompromised hematologic patients. While Candida spp and Aspergillus spp account for most cases, IFI by so-called “rare” fungi (about 1% of all IFI) are clinically relevant, with challenging diagnoses (including difficult phenotypic identification and misinterpretation as contaminants) and insufficient data on antifungal susceptibility to guide treatment guidelines. International efforts to record the epidemiology of these rare IFIs are fundamental to help overcome the lack of data that hinders successful diagnosis and treatment. Methods: We reviewed all fungal infections diagnosed in our Hematology Department in adults (18 years and over) from 06.01.2006 to 03.31.2023, selecting cases with identification of rare fungi by mycologic methods. The date of “Diagnosis” (Dx) was that of collection of the first positive sample. Results: A total of 67 patients (pts, 52.2% male) with a median age of 63.6 years (mean: 59.2, range: 23.2-90.0) were included; 68.7% had acute leukemias - 89.4% of which myeloid (AML), 13.0% lymphoblastic, 4.4% promyelocytic and 2.2% of ambiguous lineage - and 4.5% had myelodysplastic syndromes; 20.9% had a chronic lymphoproliferative disease, 3.0% had aplastic anemia and 3.0% had plasma cell dyscrasias. There was an average of 4 cases of rare IFI per year (range: 0-9), with a peak in 2017 (13.4% of total); 50.8% of all infections diagnosed over the nearly 17 years of the study occurred in the 5 years between 2013-2017, a period of renovation work in our hospital. Time to Dx ranged from 0 (collection on the day of hospitalization) to 98 days (mean: 25.4; median: 22 days). Identification of the fungus took a median of 5 days (mean: 5.6, range: 2-16 days) from the time of collection. In 8 patients (12.9%), the lab report with a fungal identification was released post-mortem; in these pts, results were available a median of 3.5 days after exitus (mean: 5.4, range: 1-13 days). In 79.1% of pts, a yeast was isolated (68.7% Geotrichum-like), while in 20.9% a filamentous fungus was identified (3.0% Mucorales). The most frequent genera were Geotrichum (62.7%), Saprochaete (5.8%), Fusarium and Alternaria (4.5% each). Cryptococcus, Trichosporon and Penicillium accounted for 3% of infections each, with 9 additional species identified in single pts. Fungemia was found in 58.2% of pts (in peripheral blood in 52.2%; in central access blood in 38.8%; in both in 32.8%). Pulmonary isolates were obtained in 26.9% of pts (in sputum in 19.4%; in bronchial aspirate or lavage in 10.4%; in both in 3.0%). Urinary isolates were found in 6.0% of pts; 13.4% had fungi in other biologic samples. The median overall survival was 20 days; 32.6% of pts died within a week of Dx, 45.6% within the first fortnight and 60.9% within the first month; 26.1% died between 1 and 3 months from Dx; and 13.0% died over 3 months after Dx. At the time of the study, 5 pts (7.5% of the cohort) were still alive, all with yeast infections; survivors had evidence of fungemia in 20% of cases and pulmonary involvement in 60%. Discussion: In our large clinical series, AML was responsible for nearly 2/3 of cases of rare IFI, reflecting its overall increased risk for IFI. The rarity of these agents was highlighted by the fact that our tertiary hematology center, serving a population of 2.3 million, had an average of 4 cases of rare IFI per year; yearly variations were in part accounted for by construction work (which releases fungal spores). Dx varied from the day of admission to over 3 months into hospitalization, reflecting a range from community-acquired to nosocomial infections; the average pt had been in hospital for 3 weeks by the time they were diagnosed. There were 4-fold more yeast infections than filamentous fungi, with Geotrichum and related yeasts accounting for 2/3 of cases. Fungemia was present in over half of patients, and pulmonary infiltrates in 1/4, a proportion that was reversed in survivors. Fungal identification took up to a fortnight, and over 10% of patients were dead before a Dx was established, not benefiting from directed treatment. The high lethality of these infections was underlined by the fact that 1/3 died within a week of Dx, with a median OS of 3 weeks. About 1/10 of pts died more than 3 months from Dx, with progressive hematologic disease being the most likely cause of death in that pt subset; less than 10% of the cohort is currently alive, and in remission.

Invasive Fungal Infections after CAR T-Cell Therapy for B-Cell Lymphoma: A Study from the French Descart Registry

Introduction: Chimeric antigen receptor (CAR) T cell therapy has emerged as an important treatment option for patients with B-cell malignancies. Despite its major clinical impact, CAR T cell therapy holds a potential risk of increased susceptibility to infections, including invasive fungal infections (IFI). Since data about the prevalence and impact of fungal infections in this population are limited, we aimed to provide a comprehensive overview of IFI using real-world data from the national DESCAR-T registry. Methods: We performed a multi-center retrospective cohort study, quering the French DESCAR-T registry (NCT04328298), to describe type, frequency and outcomes of IFI in adults with refractory or relapsed (R/R) B cell lymphomas. In addition, healthcare providers were contacted to declare any missing cases. Demographic, biological and clinical characteristics were collected retrospectively. Each IFI case was reviewed by an infectious disease specialist and a microbiologist, and classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria (Donnelly et al. Clinical Infect Dis 2020). Results: Among the 1144 patients included in the registry from 2018 to 2022, we identified 57 suspected IFI cases. After exclusion of 25 patients not adjudicated for IFI, 32 patients (3%) were identified as having presented a proven (n = 14), probable (n = 12), or possible (n = 6) IFI. DLBCL was the primary diagnosis for 30 patients and axi-cel was the most frequent CAR T product (23/32, 72%). Seven patients (22%) had received a previous hematopoietic stem cell transplantation. All patients experienced cytokine release syndrome (including 8 grade ≥ 3) and 21 (66%) experienced immune effector cell-associated syndrome (including 13 grade ≥ 3). Overall, 27 (84%), 21 (66%), and 5 (16%) received tocilizumab (median 960mg, range 120-2880mg), corticosteroids, and anakinra, respectively. Among known risk factors for IFI, grade 4 neutropenia and late neutropenia (< 1g/L) at day 28 after infusion were identified in 25 (78%) and 14 (44%) patients respectively. Overall, 8 (25%) patients received antifungal prophylaxis, posaconazole was used for 4 of them. Over half of the IFI cases occurred between 0 and 30 days after CAR T-cell infusion (18/32, 56%), with a median onset time of 29.5 days (IQR 16.5 - 79.5). The most frequently observed infections were invasive Aspergillosis (n = 13), with pulmonary involvement in 10/13 (77%) of patients, leading to a fatal issue in 3/13 patients (23%). Other mold infections included Mucormycosis (n = 5), with pulmonary involvement in 4/5 patients and a fatal outcome in 1/5, as well as Fusariosis (n = 1). Yeast infections (n = 12) were mostly identified as Candidemia (92%) with a mortality rate of 3/12 (27%). The median overall survival of patients with IFI was 186.5 days (IQR 79-506), 7 deaths being related to IFI and 3 to lymphoma relapse. Median progression-free survival was 94 days (IQR 31 - 252). Conclusions: This study represents one of the largest investigations about IFI in B-cell lymphoma patients treated with CAR T-cells. Even though IFI represent a rare complication after CAR T-cell therapy, the related-mortality is high. Selective antifungal prophylaxis may benefit high-risk patients, while rapid preemptive diagnostic workup, particularly for lung involvement, is mandatory. Analysis to define potential risk factors for IFI are ongoing.

Epidemiology and Clinical Outcomes of Hematologic Patients with Proven and Probable Invasive Fungal Infections: A Latin American Tertiary Care Centre Experience

Introduction Although diagnostic and therapeutic strategies for invasive fungal infections (IFI) have evolved in the last decade, their identification and management within patients with hematologic diseases (HD) continues to be a challenge. For this group, in addition to the increased risk of developing an IFI, mortality has been reported as high as 39.1%. The incidence and etiology vary across regions, suggesting an influence of patient-specific characteristics, environment, and clinician's practices. Literature regarding low- and middle-income countries, reflecting the real-world approach and management for this high-risk group is scarce. Our aim was to describe patients' clinical and microbiological characteristics, treatment strategies, and outcomes in a tertiary care hospital in Mexico City. Methods Retrospective single-center study that included all consecutive cases of IFI occurring in adult patients with HD or hematopoietic stem cell transplant (HSCT) between January 2013 and December 2019. We included only proven and probable cases of IFI according to the mycoses study group of the European Organization for Research and Treatment of Cancer (EORTC) guidelines. Clinical data, diagnostic work-up, treatment modalities, and outcomes were extracted from the medical records. Results In a total of 119 patients, 129 IFIs were diagnosed; criteria were fulfilled for proven in 38% ( n = 49) and probable in 62% ( n = 80). The median age was 39 years (range, 18-87) and HD was acute leukemia at 46.5%. At the time of IFI, 83.7% had active HD and 82.2% were on active treatment. HSCTs were allogeneic in 11 patients and autologous in 2 patients. A 31.8% and 91.5% presented with at least one comorbidity and/or risk factor, respectively. Severe neutropenia was present in 67.4% with a median of 13 days (range, 0-167) from the start of neutropenia to IFI diagnosis. Additional characteristics are shown in Table 1. The median time from the HD/HSCT to IFI was 73 days (range, 0-1,598); 30.2% being diagnosed within the treatment induction phase. Identified pathogenswere Aspergillus sp in 62.4%, Candida sp in 21.3%, Mucor spin10.6%, Fusarium sp in 3.5%, and Histoplasma capsulatum in 2.1%. In 10 (7.8%) cases, fungal coinfection was identified. For proven cases, sites where the microorganism was isolated or identifiedwere: blood 48.3%, lung 25.9%, sinuses 13.8%, CSF 3.4%, bone marrow 3.4%, skin 1.8%,and others 3.4%. For probable IFI, sitesof infection were: lung 91.8%, sinuses 5.9%, and other 2.4%. A 92.8% of aspergillosis and 80% of mucormycosis infections were localized in the lungs, while 86.7% of candidiasis were identified in the blood. Forty-five (35.4%) patients were receiving antifungal prophylaxis (fluconazole n = 24, itraconazole n = 13, posaconazole n = 3, voriconazole n = 3, anidulafungin n = 2). Antifungal treatment was given to24 (96.1%) of patients; 5 died before IFI diagnosis. Frontline agents included voriconazole ( n = 62), amphotericin n = 26), anidulafungin ( n = 16), caspofungin ( n = 6), fluconazole ( n = 5), clinical trial (posaconazole vs. voriconazole, n = 5) itraconazole ( n = 3), and posaconazole ( n = 1). Overall survival (OS) at 6 weeks was 59.7% and at 12 weeks was 51.9%. Overall response rate (ORR) was 48.4% ( n=60) and 54.8% ( n=68) at 6 and 12 weeks, respectively. On univariate analysis risk factors associated with increased mortality at 12-weeks were: age >40 ( p=0.001), active HD ( p = 0.020), CVC 30 days prior to IFI ( p=0.032), IMV 30 days prior to IFI ( p=0.026), and admission to ICU 30 days prior to IFI ( p=0.009). Aspergillosis was associated with reduced 12-week mortality ( p=0.001).On multivariate analysis age >40 ( p=0.010) and aspergillosis (p =0.002) remained independently associated with increased and reduced mortality, respectively. Conclusion This study reports unique information regarding proven and probable IFI in hematologic patients diagnosed under EORTC 2020 guidelines. Our epidemiology was similar to that reported by other countries, including most common etiologic agents and a higher proportion of AL and on active chemotherapy patients.Mortality rates were higher, possibly explained by the exclusion of possible IFI cases, higher proportion of active primary disease, and limited antifungal prophylaxis. Better survival among patients with aspergillosis, suggest that current diagnostic tests lead to earlier diagnosis and treatment with an impact on patients' prognosis.

Impact of invasive fungal infections in men from a state in southern Brazil: A geospatial analysis.

To analyse the records of male hospitalisation for fungal infections, including their spatial distribution and the main invasive epidemiological and sociodemographic characteristics in the State of Paraná, Brazil. Spatial analysis based on data from male admission records for invasive fungal infections (IFIs) in the State of Paraná, from 2015 to 2019. Data were taken from the hospital records obtained in the Hospital Information System of the Unified Health System, being collected, georeferenced and analysed to infer the existence of autocorrelation with the hospitalisation rates in the state. From 2015 to 2019, there were 385 cases of IFIs in men, being more prevalent in white individuals aged 61-70 years. We observed that the metropolitan, southeast, central-eastern, north-central, northwestern and western regions formed high-high clusters, with regions with a high number of registered cases. In the regression, there was an association with socioeconomic and demographic factors that showed a correlation with the rates of hospitalisation for IFIs. The study draws attention to Paraná as an endemic region for paracoccidioidomycosis, in addition to presenting high rates of nosocomial fungal infections. We also emphasise the importance of compulsory notification in the state and in the country to gain greater control over the incidence and prevalence of cases and to incentivise the creation of public policies for the prevention of IFIs.

Invasive mucorales sinusitis in a young patient with Emberger syndrome and newly diagnosed AML: A case report and literature review of invasive fungal infections in GATA2 deficiency.

Germline pathogenic variants (PVs) in the gene encoding the GATA2 transcription factor can result in profound reductions of monocytes, dendritic cells, natural killer cells and B cells. GATA2 PVs are associated with an increased risk of myeloid malignancies and a predisposition to nontuberculous mycobacterial and human papillomavirus infections. Additionally, invasive fungal infections (IFIs) have been reported in individuals with GATA2 PVs, even in the absence of myeloid malignancies. In this report, we present the case of a 40-year-old man with Emberger syndrome (GATA2 mutation, recently diagnosed acute myeloid leukaemia [AML] and history of lymphedema with hearing loss) who developed Mucorales sinusitis while receiving his first course of remission induction chemotherapy. Additionally, we review the literature on all published cases of proven IFIs in patients with GATA2 PVs. Clinicians should be aware that patients with GATA2 PVs could be vulnerable to opportunistic IFIs, even in the absence of AML and antineoplastic therapy. Furthermore, the distinctly unusual occurrence of mucormycosis during the first course of induction chemotherapy for AML in our patient indicates that patients with germline GATA2 PVs receiving induction chemotherapy for AML might be at high risk for early onset of IFIs due to aggressive, opportunistic moulds.

Invasive Fungal Infection in Hematopoietic Stem Cell Transplant Recipient from an Indian Oncology Setting

Objective Invasive fungal infections (IFI) are one of the major causes of morbidity and mortality in post-hematopoietic stem cell transplant (HSCT) recipients. Data from India is limited. The objective of this study was to analyze the incidence, risk factors, and outcomes associated with IFI in our center. Materials and Methods Adult patients, who underwent marrow/stem cell transplantation between 2014 and 2018, in an oncology center in India, were included in this single-center retrospective observational study. The revised European Organization for Research and Treatment of Cancer/ Mycoses Study Group (EORTC/MSG) consensus group 2008 definition for IFI was considered to define cases. Incidence, risk factors, and outcomes associated with IFI were analyzed. Statistical Analysis All continuous variables were represented by mean ± standard deviation and categorical variables as percentage. Comparison of categorical variables was done by either the chi-squared test or Fisher's exact test. All “p” values less than 0.05 were considered statistically significant. Results Out of the 126 patients who underwent HSCT between January 2014 and December 2018, 56 (44.4%) patients had allo-HSCT, 64 (50.8%) had auto-HSCT, and 6 (4.8%) had haplo-identical HSCT. Eighty-three (63%) patients were male and 43 (34%) females, and 113 (83.9%) Asians and 13 (10.3%) Africans. Total 111 (88%) patients received myeloablative conditioning and 24 (19%) received total body irradiation. The hematological conditions were acute myeloid leukemia (n = 23; 18.25%), acute lymphoblastic leukemia (n = 16; 12.69%), chronic myeloid leukemia (n = 4; 3.17%), Hodgkin lymphoma (n = 17; 13.4%), non-Hodgkin lymphoma (n = 11; 8.73%), myeloma (n = 35; 27.7%), sickle cell disease (n = 13; 10.31%), etc. Most patients received fluconazole (78; 61.9%) followed by micafungin (23; 18.25%), posaconazole (20; 15.87%), voriconazole (4; 3.17%), and liposomal amphotericin B (1; 0.79%) as antifungal prophylaxis. The overall rate of IFI (possible cases included) was auto-HSCT (n = 5; 7.81%), and allo-HSCT (n = 5; 8.92%). Among auto-HSCT, the IFI was proven = 0, probable n = 1 (1.5%), and possible n = 4 (6.25%) and among allo-HSCT the IFI was proven = 0, probable n = 2 (3.57%), and possible n = 3 (5.35%). No patients in haplo-HSCT had IFI. The 1-year survival rate among the IFI cases was 8/10(80%). A meaningful comparison of the risk factors and the impact of prophylactic regimens were difficult because of the very low number of IFI cases. Conclusions The overall rate of IFI in HSCT patients in our setting was low compared to global data on IFI in HSCT.

Invasive Fungal Infection Mimicking Infarctions in a Child with Acute Lymphoblastic Leukemia

Invasive fungal infection is a major cause of morbidity and mortality after intensive chemotherapy in patients with leukemia who present with febrile neutropenia. The most common sites of involvement are the lungs, sinonasal region, and disseminated blood stream infection. Visceral organ involvement is usually seen in the form of fungal abscesses, with parenchymal infarcts being less common. We report an unusual case of invasive fungal infection presenting with extensive liver infarction, global renal infarction, and multiple brain lesions in a 4-year-old boy with acute lymphoblastic leukemia on induction chemotherapy.

Breakthrough invasive fungal infection in patients with myeloid malignancy receiving posaconazole tablet prophylaxis: clinical features, risk factors, and posaconazole profiles.

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for breakthrough IFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady-state and breakthrough IFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. Ten patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P<0.001). History of allogeneic hematopoietic stem cell transplantation (OR 6.27; 95% CI 1.63-24.09), prolonged neutropenia≥28 days (OR 4.33; 95% CI 1.20-15.70), and low plasma PSC concentration<0.7μg/mL (OR 16.33; 95% CI 4.15-64.26) were risk factors for bIFI. The optimal cut-off value of plasma PSC concentration predicting bIFI was 0.765μg/mL (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablets prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.

Invasive Fungal Infection of the Duramater as the Presenting Manifestation of Disseminated Sarcoidosis (P10-10.005)

<h3>Objective:</h3> To describe a case of invasive fungal infection of the duramater which was the presenting manifestation of Disseminated sarcoidosis <h3>Background:</h3> Invasive Central nervous system fungal infections are usually encountered in the setting of immunosuppressive conditions, craniospinal trauma or instrumentation. It is rare for a treatment naïve patient with sarcoidosis to develop fungal infection of the duramater. <h3>Design/Methods:</h3> We describe the case of a young male who was found to have nodular thickening of the duramater due to Invasive CNS fungal infection. <h3>Results:</h3> We had a 27 year old man who had no prior comorbidities who presented with a single seizure. On evaluation, he was found to have nodular thickening of the Duramater. Differentials of infective, inflammatory, histiocytic and malignant conditions were considered. He underwent detailed evaluation and PET-CT revealed generalized lymphadenopathy. Biopsy from the dural thickening revealed septate hyphae and fungal culture showed Acremonium species. There were granulomas found on histopathologic examination of the dural as well as subcarinal lymphnode biopsy. He was treated with Voriconazole for 24 weeks followed by treatment of sarcoidosis. <h3>Conclusions:</h3> Sarcoidosis may be associated with immunodeficiency due to its effects on the lymphocytes, bone marrow and other organs such as the thymus. There have been several reports of patients with sarcoidosis being predisposed to infections such as Progressive multifocal leukoencephalopathy, fungal infections, tuberculosis and other bacterial infections. These infections may occur de-novo in the absence of immunosuppressant drugs or corticosteroids which have been traditionally used in the management of sarcoidosis with organ threatening or life threatening symptoms. Infections that occur as the first manifestation of an underlying autoimmune condition are challenging to diagnose. Appropriate diagnosis is essential to ensure optimum treatment of both conditions. <b>Disclosure:</b> Dr. Elavarasi has stock in Pfizer. Dr. Elavarasi has stock in PGHL. The institution of Dr. Elavarasi has received research support from All India Institute of Medical Sciences, New Delhi. The institution of Dr. Elavarasi has received research support from Indian Council for Medical Research. Dr. SINGH has nothing to disclose. Dr. CHHATTERPAL has nothing to disclose. Dr. Wig has nothing to disclose. Dr. Mittal has nothing to disclose. Mehar Chand Sharma has nothing to disclose. Dr. DAS has nothing to disclose. Ajay Garg has nothing to disclose. Dr. Jagdevan has nothing to disclose. Dr. Shamim has nothing to disclose. Dr. Tripathi has nothing to disclose. Dr. Vibha has nothing to disclose. Rajesh Kumar Singh has nothing to disclose.

Real-life comparison of posaconazole versus fluconazole for primary antifungal prophylaxis during remission-induction chemotherapy for acute leukemia

Patients undergoing remission-induction intensive chemotherapy for acute leukemia are at high risk for life-threatening invasive fungal infections (IFIs). Primary antifungal prophylaxis with posaconazole has been shown to reduce the incidence of IFI compared to fluconazole, but real-life data are limited and the effect on mortality remains unclear. This retrospective cohort study compared fluconazole and posaconazole as primary prophylaxis in real-life practice over a 10-year period, in a Canadian hospital. A total of 299 episodes were included (fluconazole, n = 98; posaconazole, n = 201), of which 68% were first inductions. The underlying hematologic malignancy was acute myeloid leukemia or myelodysplastic syndrome in 88% of episodes and acute lymphoblastic leukemia in 9%. Overall, 20 cases of IFI occurred (aspergillosis, n = 17; candidiasis, n = 3) and 14 were considered as breakthrough IFI. IFI incidence was significantly lower in the posaconazole group (3.5% versus 13.2%; p = 0.001). Empirical or targeted antifungal therapy was also reduced in the posaconazole cohort. Mortality was similar in both groups. In a real-life setting in Canada, primary posaconazole prophylaxis reduces the incidence of IFI during remission-induction chemotherapy, compared to fluconazole.

Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves.

Invasive fungal infections (IFIs) represent a severe complication of COVID-19, yet they are under-estimated. We conducted a retrospective analysis including all the COVID-19 patients admitted to the Infectious Diseases Unit of the Federico II University Hospital of Naples until the 1 July 2021. Among 409 patients, we reported seven cases of IFIs by Candida spp., seven of Pneumocystis jirovecii pneumonia, three of invasive pulmonary aspergillosis, and one of Trichosporon asahii. None of the cases presented underlying predisposing conditions, excluding one oncohematological patient treated with rituximab. Ten cases showed lymphopenia with high rates of CD4+ < 200/µL. All cases received high-dose steroid therapy (mean duration 33 days, mean cumulative dosage 1015 mg of prednisone equivalent), and seven cases had severe COVID-19 disease (OSCI ≥ 5) prior to IFI diagnosis. The cases showed a higher overall duration of hospitalization (63 vs 24 days) and higher mortality rate (23% vs. 7%) compared with the COVID-19 patients who did not developed IFIs. Cases showed a higher prevalence of high-dose steroid therapy and lymphopenia with CD4+ < 200/µL, primarily due to SARS-CoV-2 infection and not related to underlying comorbidities. IFIs strongly impact the overall length of hospitalization and mortality. Therefore, clinicians should maintain a high degree of suspicion of IFIs, especially in severe COVID-19 patients.

Invasive Fungal Infections in Acute Haematological Malignancies: A Cross-sectional Study

Introduction: Fungal infections are common complications of acute haematological malignancies i.e. acute myeloid and acute lymphoblastic leukaemia. The cells in these two groups are different morphologically and immunologically. Hence the interaction with the different types of fungi may vary. Aim: To identify the acute leukaemia cases and fungal infection among myeloid and lymphoid groups and to find out association of types of invasive fungal infection according to cell line affected. Materials and Methods: A cross-sectional observational hospital-based prospective study was conducted in a risk group of acute haematological malignancy over a period of six months from July 2021 to December 2021 in a tertiary care Hospital, Medical College Kolkata, West Bengal, India. Study tools were questionnaire based on European Organisation for Research and Treatment of Cancer /Mycoses Study Group (EORTC/MSG) criteria, clinical reports and standard laboratory procedures were practiced in Microbiology laboratory. The data was entered in excel spreadsheet and analysed using Statistical Package for the Social Sciences (SPSS) 28th version. Results: A total of 24 cases of Invasive Fungal Infections (IFI) were observed out of the 78 patients included in the study. This corresponds to an IFI prevalence of 30.77%. Patients with proven IFI constituted 8 (33.33%), probable IFI accounted for 15 (62.5%) where as those with possible IFI accounted for 1 (4.2%) of total IFI cases. There were age and sex wise variation in IFI. The prevalence of IFI was found to be higher in Acute Myeloid Leukaemia (AML) (48.5%) patients as compared to Acute Lymphoblastic Leukaemia (ALL) (19.14%). Of all AML patients invasive candidiasis was the most common type followed by aspergillosis. In ALL patients invasive candidiasis also constituted 44.44% followed by dematiaceous mycosis, followed by aspergillosis. Conclusion: AML patients suffer more from IFI than ALL ones. Invasive non albicans candidiasis affected both types but more incidence was seen in AML affected group. Aspergillus spp. affected lungs of both groups but dematiaceous fungi were isolated only from ALL affected paediatric patients and in samples other than pulmonary or blood sample.

A case of invasive fungal infection triggered by treatment of superior vena cava syndrome caused by tongue squamous cell carcinoma

A case of invasive fungal infection triggered by treatment of superior vena cava syndrome caused by tongue squamous cell carcinoma

Perineural spread of rhino-orbito-cerebral mucormycosis in post-Covid-19 patients-Description of this rare pathwayin the rural population of southern Rajasthan

Various opportunistic infections were found to be more common in patients with a history of Covid-19 infection after the second wave of pandemic. The rural and tribal population was severly hit due to quack practices, lack of health care, and knowledge. Clinical features range from non-invasive sinusitis to aggressive invasive form in immunocompetent hosts. Rhino-orbito-cerebral mucormycosis (RCOM) is a very infrequent but lethal fungal infection, usually affecting diabetic patients (Ketoacidosis state). It has characteristic patterns of spread, i.e., continuous, direct spread or via vascular invasion, while perineural spread being the least common pathway of invasion. We report nine cases of invasive fungal infection with an symptomatic perineural spread in this study.

Evaluation of Panfungal Polymerase Chain Reaction in Early Detection of Invasive Fungal Infections in Egyptian Patients with Hematological Malignancies.

The incidence of invasive fungal infections (IFIs) has increased owing to the rising number of immunodeficient patients. A case-control study was performed at the Ain Shams University Hospitals, Cairo, Egypt. The case group (n = 80) included 80 patients diagnosed with hematological malignancies, and the control group (n = 20) included 20 patients. All patients were tested for the presence of fungal species using blood culture and panfungal real-time polymerase chain reaction (RT-PCR). Fungal species differentiation was performed using high-resolution melting (HRM) PCR. There were 39 suspected cases of IFIs among the 80 patients. The panfungal RT-PCR detection rate was 51.3% (41/80). HRM-PCR identified that 51.2% of the fungal species were Candida albicans, 44.0% were non-Candida albicans, and 4.9% were Mucor. The blood cultures were positive for the presence of fungi in two patients with acute myeloid leukemia. The fungal detection rate using the panfungal RT-PCR technique was significantly higher than that using the blood culture technique (P < 0.001). RT-PCR using panfungal markers is sensitive, rapid, and superior to the blood culture technique to detect IFIs. HRM-PCR is a specific test for species identification.

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a form of cancer that is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells of the hematopoietic system. Patients with acute myeloid leukemia (AML) receiving azacitidine (AZA) alone or in combination with venetoclax (VEN-AZA) are at increased risk for invasive fungal infections (IFIs). We compared the incidence and risk of IFI during these treatment regimens in a single Taiwan hospital. A total of 61 patients with AML received at least one course of AZA in the hematology ward of China Medical University Hospital (Taichung, Taiwan) between September 2012 and June 2020. Thirty-eight patients (62.3%) received AZA monotherapy; 23 (37.7%) received VEN-AZA. Incidence rates of probable and proven IFI were 18% and 1.6%, respectively, during AZA treatment. One proven case of Fusarium spp. infection was isolated by skin and soft tissue culture. Most (75%) IFI cases occurred during the first cycle of AZA therapy. Half of all IFI cases occurred in patients with prolonged neutropenia. The risk of IFI was significantly higher for the European LeukemiaNet (ELN) nonfavorable-risk group (intermediate- and adverse-risk group) versus the ELN favorable-risk group and for patients with prolonged neutropenia versus those without (P<0.05 for both comparisons). In this study, median OS did not differ significantly between patients with and without IFIs during AZA-containing regimens (14.6 months vs 13.7 months; P=0.59). The incidence of IFI was high in this AML cohort treated with AZA-containing regiments in Taiwan. The majority of IFI cases occurred during the early cycles of AZA (cycles 1-2). Prospective studies are needed to determine the optimal choice of antifungal prophylaxis agent during VEN-AZA therapy for AML.

Risk Factors for Invasive Fungal Disease in Pediatric Oncology

Background: Invasive fungal infections are a major cause of death in pediatric oncology, especially among patients under chemotherapy. This study aims to identify risk factors for invasive fungal infections in pediatric oncology. Methods: We conducted a monocentric retrospective case-control multi-cohort study on a population of 30 patients with malignant hemopathies or solid cancers under chemotherapy, admitted in the Pediatric Oncology unit of Nafissa Hammoud Hospital in Algiers, amongst which 24 patients were controls, and 6 patients were cases. Results: In a total of 30 patients (53.3 % male), 13 patients developed a fever, from which 6 patients were identified as invasive fungal infection cases according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Infectious Diseases Mycoses Study Group (EORTC/MSG) guidelines, with an incidence of 20 %. The mean age was 7.47 years old at the admission date. Four statistically significant risk factors were identified (p-value &lt; 0.05, CI 95 %): mucositis with an odds ratio (OR) at 10 (1,34 – 74,51), the most aggressive chemotherapy protocol according to the ITR2 with an OR at 115 (6,10 – 2165,95), severe prolonged neutropenia with an OR at 7,6 (1,07 – 54,09) and severe prolonged lymphopenia with an OR at 25 (2,27 – 275,71). Conclusion: Many conditions were identified as risk factors for invasive fungal infections in pediatric oncology, especially severe lymphopenia and aggressive chemotherapy. These patients may have to receive close monitoring or even antifungal prophylaxis.