Risk Factors For Invasive Aspergillosis Research Articles

Diagnostic significance of bronchoalveolar lavage galactomannan assay in invasive aspergillosis: A comprehensive analysis

Background: In critically ill and immunocompromised patients, diagnosing invasive aspergillosis (IA) is crucial. This study focuses on theGalactomannan (GM) Antigen Test. The study categorizes GM-positive patients into two groups based on bronchoalveolar lavage fluid GM levels: Group 1 (GM index >1.5) and Group 2 (GM index >0.5-1.5). Aim: This study aims to investigate the association between GM levels in bronchoalveolar lavage fluid and clinical outcomes in IA patients, specifically focusing on mortality rates. Additionally, the study explores the role of C-reactive protein (CRP) levels, type 2 diabetes mellitus, and chronic kidney disease (CKD) as key risk factors for IA. Methods: Patients with GM-positive results were divided into Group 1 and Group 2 based on GM index levels. The study assessed age, sex distribution, and mortality rates in these groups. Results: While there were no significant differences in age and sex distribution between Group 1 and Group 2, a higher mortality rate was observed in Group 1, aligning with established clinical expectations. The study highlights the importance of categorizing GM interpretations based on these two groups. CRP levels, along with comorbidities like type 2 diabetes mellitus and CKD, emerged as key risk factors for IA. Conclusion: This research emphasizes the significance of GM levels in bronchoalveolar lavage fluid as a prognostic indicator for IA, especially when categorized into GM index groups. The study contributes valuable insights into mortality rates and identifies CRP levels, type 2 diabetes mellitus, and CKD as crucial risk factors. These findings enhance our understanding of IA diagnostics and risk stratification.

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality.

Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation. To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA). In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group. The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero). In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

COVID-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study.

The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to A. fumigatus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.

Comparison of the Results of Galactomannan and Beta Glucan Antigen Tests in the Suspicion of Invasive Pulmonary Aspergillosis

Opportunistic fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Invasive aspergillosis (IA) has an important place among these infections with ~ 250.000 cases annually. Reducing the mortality rate due to invasive aspergillosis is possible with early diagnosis and treatment of the disease. Because of the low sensitivity in microscopic examination, the time consuming of culture growth, and the difficulties in distinguishing colonization/infection, serological methods are frequently used in the diagnosis of invasive aspergillosis. The aim of this study was to determine the diagnostic performance of galactomannan and beta glucan tests for the diagnosis of invasive pulmonary aspergillosis (IPA). Sixty patients, followed up with the suspicion of invasive pulmonary aspergillosis in Gazi University Hospital were included in the study. The clinical classification of the patients was made according to the revised European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria. A total of 10 patients were classified as probable invasive aspergillosis and 20 patients were classified as possible invasive fungal disease. Demographic data of the patients and various risk factors were recorded. One hundred and thirty serum and nine bronchoalveolar lavage (BAL) fluid samples were studied with Plateliaᵀᴹ Aspergillus Ag (Bio-Rad, France), Dynamiker Aspergillus Galactomannan and Dynamiker Fungus (1-3)-beta-D-Glucan (Dynamiker, China) kits. Sensitivity and specificity values were calculated according to U.S. Food and Drug Administration (FDA) approved Plateliaᵀᴹ Aspergillus Ag test. According to this study, the most important risk factors in the development of IPA were the use of steroids and immunomodulatory drugs. The sensitivity of the galactomannan test in the probable group was 77.8%, the specificity was 96.7%, the sensitivity of the beta glucan test was 61.1%, and the specificity was 92.6%. When these two tests were evaluated together, it was observed that the sensitivity in the probable group increased to 83.3% and the specificity decreased to 89.3%. The combined use of galactomannan and beta glucan tests increases the diagnostic sensitivity. Although the presence of prolonged neutropenia is an important risk factor for IA, the use of steroids and immunomodulatory drugs should be kept in mind in non-neutropenic patients.

Invasive Aspergillosis after Renal Transplantation.

Over 95,000 renal transplantation procedures were completed in 2021. Invasive aspergillosis (IA) affects about 1 in 250 to 1 in 43 renal transplant recipients. About 50% of cases occur in the first 6 months after transplantation; the median time of onset is nearly 3 years. Major risk factors for IA include old age, diabetes mellitus (especially if prior diabetic nephropathy), delayed graft function, acute graft rejection, chronic obstructive pulmonary disease, cytomegalovirus disease, and neutropenia. Hospital construction, demolition activities, and residential refurbishments also increase the risk. Parenchymal pulmonary infection is the most common (~75%), and bronchial, sinus, cerebral, and disseminated disease are less common. Typical pulmonary features of fever, dyspnea, cough, and hemoptysis are seen in most patients, but 20% have non-specific general features of illness. Non-specific infiltrates and pulmonary nodules are the commonest radiological features, with bilateral disease carrying a worse prognosis. Bronchoscopy for direct microscopy, fungal culture, and Aspergillus antigen are the fastest means of establishing the diagnosis; a positive serum Aspergillus antigen presages a worse outcome. Standard therapy includes voriconazole, isavuconazole, or posaconazole, with great attention necessary to assess likely drug-drug interactions. Liposomal amphotericin B and echinocandins are less effective. A reduction in or stopping immunosuppression needs careful consideration, given the overall mortality of IA in renal-transplanted patients; continuing corticosteroid after the diagnosis of IA increases mortality by 2.5 times. Surgical resection or the addition of a gamma interferon should also be considered.

Risk Factors and Outcomes of Invasive Aspergillosis in Kidney Transplant Recipients: A Case-Control Study of United States Renal Data System Data.

Kidney transplant recipients are at increased risk for invasive aspergillosis (IA), a disease with poor outcomes and substantial economic burden. We aimed to determine risk factors for posttransplant IA by using a national database and to assess the association of IA with mortality and allograft failure. Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2017. To evaluate risk factors for IA, we performed conditional logistic regression analysis by comparing characteristics between IA-infected patients and their matched uninfected controls. We performed Cox regression analysis to evaluate the effects of IA on mortality and death-censored allograft failure. We matched 359 patients with IA to 1436 uninfected controls (1:4). IA was diagnosed at a median of 22.5 months (interquartile range, 5.4-85.2 months) after kidney transplant. Risk factors for IA were Black/African American race, duration of pretransplant hemodialysis, higher Elixhauser Comorbidity Index score, weight loss, chronic pulmonary disease, need for early posttransplant hemodialysis, and a history of cytomegalovirus infection. Receiving an allograft from a living donor was protective against IA. IA was a strong independent predictor of 1-year mortality (adjusted hazard ratio [aHR], 5.02 [95% confidence interval {CI}, 3.58-7.04], P < .001). Additionally, IA was associated with 1-year allograft failure (aHR, 3.37 [95% CI, 1.96-5.77], P < .001). Our findings emphasize the importance of timely transplant to mitigate the risk of posttransplant IA. An individualized approach to disease prevention is essential to decrease mortality and allograft failure.

Influenza vaccination is associated with a reduced risk of invasive aspergillosis in high-risk individuals in Taiwan: a population-based cohort study

ABSTRACT Invasive aspergillosis (IA) has become the emerging life-threatening disease in recent years. Influenza has been identified as an independent risk factor for IA. Vaccination is the most effective way to prevent influenza, while whether it can reduce IA in high-risk population still uncertain. We aimed to investigate the association between influenza vaccination and the risk of IA in high-risk population. We performed a population-based cohort study of people who qualified for government-funded influenza vaccination and were at high risk for IA at the start of the influenza season each year between 2016 and 2019. We utilized Taiwan’s National Health Insurance Research Database to identify the influenza vaccination status and IA diagnosis during the follow-up period. We compared the risk of IA between people with and without vaccination using multivariable logistic regression analysis. Out of total 8,544,451 people who were eligible during the 3 influenza seasons, 3,136,477 (36.7%) were vaccinated. A total of 1179 IA cases with the incidence of 13.8 cases per 100,000 high-risk individuals were identified during the follow-up. Compared to non-vaccinated group, vaccinated individuals had a 21% risk reduction of IA (adjusted odds ratio 0.79, 95% confidence interval 0.70–0.90). Influenza vaccination was associated with a lower risk of IA among males, immunosuppressive conditions, malignancy, diabetes, and those having host factors according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Influenza vaccination is recommended for high-risk population to reduce the risk of IA.

Neutrophil and Macrophage NADPH Oxidase 2 Differentially Control Responses to Inflammation and to Aspergillus fumigatus in Mice.

Aspergillus fumigatus is an important opportunistic fungal pathogen and causes invasive pulmonary aspergillosis in conditions with compromised innate antifungal immunity, including chronic granulomatous disease, which results from inherited deficiency of the superoxide-generating leukocyte NADPH oxidase 2 (NOX2). Derivative oxidants have both antimicrobial and immunoregulatory activity and, in the context of A. fumigatus, contribute to both fungal killing and dampening inflammation induced by fungal cell walls. As the relative roles of macrophage versus neutrophil NOX2 in the host response to A. fumigatus are incompletely understood, we studied mice with conditional deletion of NOX2. When NOX2 was absent in alveolar macrophages as a result of LysM-Cre-mediated deletion, germination of inhaled A. fumigatus conidia was increased. Reducing NOX2 activity specifically in neutrophils via S100a8 (MRP8)-Cre also increased fungal burden, which was inversely proportional to the level of neutrophil NOX2 activity. Moreover, diminished NOX2 in neutrophils synergized with corticosteroid immunosuppression to impair lung clearance of A. fumigatus. Neutrophil-specific reduction in NOX2 activity also enhanced acute inflammation induced by inhaled sterile fungal cell walls. These results advance understanding into cell-specific roles of NOX2 in the host response to A. fumigatus. We show that alveolar macrophage NOX2 is a nonredundant effector that limits germination of inhaled A. fumigatus conidia. In contrast, reducing NOX2 activity only in neutrophils is sufficient to enhance inflammation to fungal cell walls as well as to promote invasive A. fumigatus. This may be relevant in clinical settings with acquired defects in NOX2 activity due to underlying conditions, which overlap risk factors for invasive aspergillosis.

P144 The uncommon meets the common: Invasive Aspergillosis and tuberculosis co-infection in non-neutropenic patients— arare association

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground and ObjectiveInvasive aspergillosis (IA) is known to occur in immunocompromised patients including neutropenic patients. But, recently increasing cases have been reported in patients with non-classical risk factors and non-neutropenic patients like diabetes mellitus, chronic lung disease, HIV infection, critically ill patients, etc. According to ISHAM these non-classical risk factors should be included in EORTC/MSG host criteria for diagnosis of invasive aspergillosis.India has a high tuberculosis (TB) burden, and this is always considered as the first differential for any patient with fever, cough, hemoptysis, and weight loss. Post-tubercular chronic pulmonary aspergillosis common reported condition. However, co-infection of active TB and invasive aspergillosis is less reported. This co-infection could be one of the contributors of high morbidity and mortality in cases with tuberculosis.We hereby present a series of five cases of TB concomitant with invasive aspergillosis in non-neutropenic patients.MethodsThis is a prospective observational study, all patients admitted with molecular diagnosis (GeneXpert) of tuberculosis and with at least one non-classical risk factor for invasive aspergillosis were subjected to further evaluation. Diagnosis of invasive aspergillosis was considered in patients who had at least one clinical and one mycological EORTC criteria. Galactomannan level in different samples was measured via PlateliaTM ELISA. The efficacy of different antifungals and outcomes were analyzed.ResultsTotal 57 patients with TB underwent for evaluation of invasive aspergillosis. Among them, five patients were diagnosed to have concomitant TB and invasive aspergillosis, of which three cases of CNS TB and CNS aspergillosis and two had concomitant pulmonary infections. The average age was 31 ± 12 years with a female preponderance (4/5). Two patients were HIV positive, while among non-HIV patients, one had CD4 cytopenia (CD4-171). One patient had no known predisposing factor. Radiologically, most common pulmonary lesions were patchy consolidation with centrilobular nodules with tree in bud appearance, while CNS lesions showed multiple ring-enhancing lesions. All the patients had CBNAAT positive, two from BAL sample, 1 from CSF, and 1 from the lymph node. Rifampicin was sensitive in all, except one who had rifampicin resistance indeterminate. Of these patients, four were probable invasive aspergillosis satisfying the host, mycological and clinical factors as per the EORTC/MSGERC 2021 guidelines. The treatment of coinfection is challenging due to the interaction of rifampicin with voriconazole, which is the drug of choice for invasive aspergillosis. Here, 3 patients were treated with Inj amphotericin B, while the other 2 patients were started on voriconazole with rifampicin sparing regimen for TB. Of the 5 patients, 4 patients survived with excellent response to the treatment, with one fatality.ConclusionThe possibility of concurrent TB and invasive aspergillosis in non-neutropenic hosts should be considered to avoid devastating outcomes. The lack of clinical suspicion may result in misdiagnosis, and most importantly, the chronicity of the infection makes it indistinguishable from TB. Moreover, the co-administration of antifungal and anti-TB medications presents significant therapeutic challenges necessitating thorough evaluation and monitoring.

Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis.

BackgroundThis study aimed to investigate the Aspergillus species distribution, antifungal sensitivities, clinical characteristics, and risk factors of patients with invasive aspergillosis (IA) in a tertiary teaching hospital in Anhui Province.MethodsIn the present study, 156 Aspergillus isolates were collected from patients admitted to a 2,800-bed comprehensive hospital between January 2019 and April 2021. The epidemiology of Aspergillus species was well-examined, and its antifungal susceptibility was specifically measured by the microbroth dilution method. The risk factors of patients with IA were documented and analyzed intensively. In addition, gene sequencing was employed to determine gene mutations of cytochrome P450 14-α sterol demethylase-Aspergillus (cyp51A) associated with azole resistance among Aspergillus fumigatus.ResultsThe Aspergillus species distribution was dominated by A. fumigatus (56.41%), Aspergillus flavus (20.51%), and Aspergillus niger (15.38%) locally. In particular, all Aspergillus species showed very low minimum inhibitory concentrations (MICs, ≤ 0.5 μg/ml) for azoles and echinocandins, slightly high MICs (1.66–2.91 μg/ml) for amphotericin B, and exceptionally high MICs (>64 μg/ml) for flucytosine. Azole-resistant rate of Aspergillus species in this local region reached up to 5.79%. Correlation analyses of multiple antifungals indicate a significant MIC relevance between isavuconazole and voriconazole (Pearson correlation coefficient was 0.81, P < 0.0001). The clinical risk factors for patients with IA were found primarily to be pulmonary diseases (P = 0.007) and patients' age (P < 0.001). Notably, three mutant loci (TR46/Y121F/T289A) of the cyp51A gene were identified in azole-resistant A. fumigatus.ConclusionsThe Aspergillus species emerged increasingly, of which A. fumigatus and A. flavus remained the main pathogens for invasive Aspergillus infections in the local region. The vast majority of Aspergillus species exhibited good susceptibility to all the antifungals, except flucytosine. The local occurrence of azole-resistant Aspergillus species grew gradually and needed monitoring in time. Pulmonary diseases and age were likely considered as highly associated risk factors for IA. To our knowledge, the clinically isolated azole-resistant A. fumigatus with TR46/Y121F/T289A mutations identified here were rarely reported in the area of China.

Clinical and Epidemiological Profile of Patients with Invasive Aspergillosis from a Fourth Level Hospital in Bogota, Colombia: A Retrospective Study.

Invasive aspergillosis (IA) is a severe mycosis caused by Aspergillus species. The infection mainly affects immunocompromised patients with a significant clinical burden. This study aimed to determine the clinical and epidemiological characteristics of patients diagnosed with IA in a fourth level hospital in Colombia, as these data are scarce in the country. A retrospective, observational study, from a single center was conducted with 34 male and 32 female patients, between 1 month- and 90-year-old, diagnosed with proven (18.2%), probable (74.2%) and possible (7.6%) IA, during a 21-year period. The most frequent underlying conditions for IA were chemotherapy (39.4%) and corticosteroid use (34.8%). The lung was the most common affected organ (92.4%). Computed tomography (CT) imaging findings were mainly nodules (57.6%) and consolidation (31.8%). A low positive correlation was found between serum galactomannan and hospitalization length. Aspergillus fumigatus prevailed (73.3%) in sputum and bronchoalveolar lavage cultures. Most patients were hospitalized in general wards (63.6%) and treated with voriconazole (80.3%). Mortality rate was 15.2%. Common risk factors for IA were identified in the Colombian cohort, including medications and underlying diseases. However, their frequency differs from other countries, reinforcing the idea that local surveillance is essential and at-risk patients should be carefully monitored.

Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit With Coronavirus Disease 2019: A Multicenter Retrospective Study.

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality.Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed.Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0–42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16–3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80–7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02–2.79, p = 1.02–2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA.Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

Aspergillosis: Emerging risk groups in critically ill patients.

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

Prevalence and Clinical Risk Factors for Invasive Aspergillosis in Patients with Acute Leukemia at Srinagarind Hospital, Khon Kaen University

Objective: Invasive aspergillosis (IA) is the most common fungal infection in patients with acute leukemia and associated with high mortality rate. We aimed to report the prevalence and clinical risk factors of IA in patients with acute leukemia at Srinagarind Hospital, Khon Kaen University. Materials and Methods: A retrospectively study was performed in adult acute leukemia patients who were diagnosed with IA from January 2006 to December 2015 at Srinagarind Hospital, Khon Kaen University. IA was defined by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group. Clinical characteristics and laboratory data were analyzed. Multivariate logistic regression analysis was used to determine the associations. Results: A total of 355 patients with acute leukemia, invasive aspergillosis was found in 39 patients (11%). The median age was 46 years (IQR of 33 to 59 years). Gender distribution was equal between males and females. Most common type of leukemias in the study are acute myeloid leukemia non-M3 (50.7%), followed by acute myeloid leukemia M3 (24.8%), and acute lymphoblastic leukemia (24.8%) respectively. Using logistic regression analysis, patients who had neutropenia at the time of IA diagnosed (adjusted OR 3.54; p=0.014), hepatitis B viral infection (adjusted OR 3.13; p=0.03), and working as construction worker (adjusted OR 23.08; p&lt;0.001) remained the risk factor of IA. Conclusion: The prevalence of IA in Thai patients with acute leukemia is modest. Neutropenia, hepatitis B viral infection and construction worker were significant clinical risk factors for IA in patients with acute leukemia. Keywords: Invasive aspergillosis; Acute leukemia; Srinagarind Hospital

Risk factors of invasive fungal infections in lung transplant recipients: A systematic review and meta-analysis

Invasive fungal infection (IFI) remains a common complication after lung transplantation, causing significant morbidity and mortality. We have attempted to quantify systematically risk factors of IFI in lung transplant recipients. Studies were retrieved from Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews and Cochrane central register of controlled trials. All case-control and cohort studies evaluating the risk factors of IFI in adult lung transplant recipients were screened. Two researchers reviewed and assessed all studies independently. We pooled the estimated effect of each factor associated with IFI by using a random effect model. Eight studies were included in the systematic review and 5 studies were eligible for the meta-analysis. Rates of IFI range from 8% to 33% in lung transplant recipients. Independent risk factors for invasive aspergillosis (IA) in lung transplantation include previous fungal colonization (odds ratio [OR] 2.44; 95% confidence interval [CI] 0.08-0.47), cytomegalovirus infection (OR 1.96; 95% CI 1.08-3.56), and single lung transplantation (OR 1.77; 95% CI 1.08-2.91). Pre-emptive antifungal therapy is a protective factor for IA in lung transplant (OR 0.2; 95% CI 0.08-0.47). Cytomegalovirus infection, previous fungal colonization and single lung transplantation independently increase the risk of IA in lung transplant recipients. Pre-emptive antifungal therapy is a protective factor for IA in the lung transplant population.

Suppression effect of thyme and carvacrol nano-emulsions on Aspergillus fumigatus isolated from patients in the intensive care unit of Assiut University Hospital, Egypt

Background and Aim: Aspergillus fumigatus is a zoonotic fungus that causes several diseases in humans ranging from allergic reaction to fatal disseminated invasive infection, especially in immunocompromised patients. This study aimed to investigate the incidence of invasive A. fumigatus in patients admitted to the intensive care unit (ICU) of Assiut University Hospital, highlight the factors associated with their infection, and determine the antifungal effect of thyme nano-emulsion (TNE) and carvacrol nano-emulsion (CNE) on isolated A. fumigatus strains. Materials and Methods: Mycological culture method and scanning electron microscopy (SEM) were used in the identification of A. fumigatus in 630 blood samples collected from 210 patients. TNE and CNE at five concentrations (1%, 2%, 4%, 6%, and 8%) and average sizes of 90.3 and 75.6 nm, respectively, were characterized by transmission electron microscopy. Their effect on A. fumigatus isolate growth was evaluated by the well-diffusion method and SEM, which was used for the detection of the degenerative effect of A. fumigatus ultrastructure. Results: A. fumigatus was detected in 54 of 210 (25.7%) patients in the ICU. Advanced age and chronic diseases were considered important risk factors for invasive aspergillosis, especially in patients with more than 1 clinical disease. TNE and CNE showed an inhibitory effect on A. fumigatus isolates, which significantly increased with high concentrations. The respective values for TNE at concentrations of 6% and 8% were 6±0.41 mm and 15±0.67 mm. CNE completely inhibited A. fumigatus growth at concentrations of 4%, 6%, and 8%, while mean inhibition zones of 22±0.68 mm and 30±0.32 mm appeared at concentrations of 1% and 2%. SEM demonstrated degenerative changes in A. fumigatus structure. Conclusion: TNE and CNE can be used in bioactive treatments against A. fumigatus, and additional studies are required to determine the safe and effective doses and best method for application in human and veterinary medicine.

Invasive aspergillosis in adult patients with rheumatic diseases

Objective: to study risk factors for invasive aspergillosis (IA), its etiology, clinical manifestations, and treatment efficiency in patients with rheumatic diseases (RD).Patients and methods. The first study of proven and probable IA (EORT/MSGERC, 2019) was conducted in 18 patients with RD, who accounted for 3% of all adult IA patients (n=699) included in the 1998–2020 registry of the Department of Clinical Mycology, Allergology, and Immunology, I.I. Mechnikov North-Western State Medical University (Group 1). This group comprised 56% women; the median age was 59 [21; 75] years. Group 2 (a comparison group) included 610 adult hematology patients with IA (median age, 45 [18; 79] years; 42% women). A prospective case-control study was conducted to identify risk factors for IA in patients with RD: 36 rheumatic patients without IA (median age, 58 (18–79) years; 61% women) (a control group).Results and discussion. Patients with RD were found to often develop IA in the presence of anti-neutrophilic cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) and systemic lupus erythematosus (50 and 16%, respectively). It was shown for the first time that the likelihood of IA in patients with RD increases with prolonged (median 14 days) lymphocytopenia during RD treatment (odds ratio 13.0; 95% confidence interval, 3.3–50.3). The main causative agents of IA were A. fumigatus (50%) and A. niger (29%). IA was more severe in Group 1 than in Group 2: in the resuscitation and intensive care units, there were 44 and 18%, respectively (p=0.01). Group 1 versus Group 2 more frequently had respiratory failure (61 and 37%, respectively; p=0.03), hemoptysis (28 and 7%; p=0.0001), chest pain (17 and 7%; p=0.04), and cardiac involvement (11 and 1%; p=0.0001), and less frequently had fever (67 and 85%; p=0.01). The common site of IA was the lung (83%); the characteristic feature detected by computed tomography (CT) is pulmonary cavitation (44%). Antifungal therapy was used in 89% of Group 1 patients; the overall 12-week survival was 69%.Conclusion. In patients with RD, it is difficult to differentiate between the progression of the underlying disease, adverse drug reactions, infectious complications, or a combination of these disorders due to the similarity of their clinical manifestations. When RD patients with infectious syndrome and respiratory failure develop prolonged lymphocytopenia during combination therapy, AI should be suspected and lung CT, bronchoscopy, and mycological examination of the material obtained by bronchoalveolar lavage be done.

Nationwide Trends and Outcomes in Neutropenic Acute Leukemia Patients with Invasive Aspergillosis

Background: Invasive aspergillosis (IA) is one of the most dreaded complications in neutropenic patients with hematologic malignancies; risk significantly increases with chemotherapy, particularly during induction. It dramatically worsens the overall prognosis of the underlying malignancy and predisposes patients to undergo secondary interventions, thereby prolonging the duration of treatment and hospital stay. While prophylactic antifungal therapy has remarkably lowered the rates of IA, it remains a persistent problem in cancer treatment. The primary objective of our study is to explore the risk factors of IA in neutropenic patients with acute leukemias and its role in hospital stay, in-hospital mortality, and hospitalization costs. Methods: The Nationwide Inpatient Sample (NIS) database was queried to include all adults with acute leukemia admitted from 2012 and 2017, whose course was complicated by neutropenia. Those with and without invasive aspergillosis were compared. T-test was used to compare means of continuous variables and chi-square test to compare proportions of categorical variables. Multivariable logistic regression was used to evaluate risk factors for aspergillosis, as well as, inpatient mortality. Statistical tests for trends of resource utilization across six years were performed. Results: A total of 141,835 admissions met the inclusion criteria, of which, 2.5% had aspergillosis. Mean age (55.4 years) and gender (male 55.5%) did not significantly differ in neutropenic patients with and without aspergillosis. AML accounted for a larger proportion of the aspergillosis group (84.3% vs 76.9%, p&amp;lt;0.0001). Rates of HSCT and inpatient chemotherapy were comparable in both groups. Those with aspergillosis had higher inpatient mortality (15.8% vs 7.1%, p&amp;lt;0.0001) and more frequently required ICU-level care (12.9% vs 5.4%, p&amp;lt;0.0001) Independent risk factors for the development of aspergillosis included: Black race, receiving treatment at a teaching hospital, AML (compared to ALL) and poor nutritional status. On multivariate analysis, aspergillosis conferred an increased risk of inpatient mortality (aOR 2.57, 95% CI: 2.08-3.19, p&amp;lt;0.001), longer length of hospital stay by 7.4 days (95% CI: 6.0 to 8.8 days, p&amp;lt;0.001) and higher hospitalization costs by $37k per admission (95% CI: $29k-44k, p&amp;lt;0.001). Rates of aspergillosis decreased from 2.9% in 2012 to 2.2% in 2017 (trend P=0.03). In neutropenic acute leukemia patients without aspergillosis, there has been an improvement in inpatient mortality (from 7.3% in 2012 to 6.0% in 2017, trend P &amp;lt;0.01), as well as, length of hospital stay (17.5 days in 2012 to 16.7 days in 2017, trend P=0.02). However, there was no significant change in mortality or resource utilization among those with aspergillosis. Conclusions: Aspergillosis represents a significant challenge in the management of hematological malignancies. There is a delicate interplay between neutropenia and IA, with neutropenic patients more susceptible to invasive fungal infections, and IA further contributing to neutropenia. The encouraging trend in decreasing prevalence along the years is reflective of more aggressive prophylactic antifungal usage in acute leukemias, with the revised IDSA guidelines for aspergillosis being a cornerstone. However, mortality and resource utilization remain unchanged despite advances in diagnosis and treatment of aspergillosis. This data highlights the importance of prophylactic antifungals and maintaining a high index of suspicion for IA in neutropenic acute leukemia and the need of early focused treatment to improve clinical outcomes. Disclosures No relevant conflicts of interest to declare.

COVID-19 associated with pulmonary aspergillosis: A literature review.

Bacterial or virus co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in many studies, however, the knowledge on Aspergillus co-infection among patients with coronavirus disease 2019 (COVID-19) was limited. This literature review aims to explore and describe the updated information about COVID-19 associated with pulmonary aspergillosis. We found that Aspergillus spp. can cause co-infections in patients with COVID-19, especially in severe/critical illness. The incidence of IPA in COVID-19 ranged from 19.6% to 33.3%. Acute respiratory distress syndrome requiring mechanical ventilation was the common complications, and the overall mortality was high, which could be up to 64.7% (n = 22) in the pooled analysis of 34 reported cases. The conventional risk factors of invasive aspergillosis were not common among these specific populations. Fungus culture and galactomannan test, especially from respiratory specimens could help early diagnosis. Aspergillus fumigatus was the most common species causing co-infection in COVID-19 patients, followed by Aspergillus flavus. Although voriconazole is the recommended anti-Aspergillus agent and also the most commonly used antifungal agent, aspergillosis caused by azole-resistant Aspergillus is also possible. Additionally, voriconazole should be used carefully in the concern of complicated drug–drug interaction and enhancing cardiovascular toxicity on anti-SARS-CoV-2 agents. Finally, this review suggests that clinicians should keep alerting the possible occurrence of pulmonary aspergillosis in severe/critical COVID-19 patients, and aggressively microbiologic study in addition to SARS-CoV-2 via respiratory specimens should be indicated.

Risk factors for the development of invasive aspergillosis after kidney transplantation: Systematic review and meta-analysis.

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR]=7.26; 95% confidence interval [CI]=1.05-50.06) and among those with diabetic nephropathy (OR=1.65; 95% CI=1.10-2.48). Requiring posttransplant hemodialysis (OR=3.69; 95% CI=2.13-6.37) or surgical reintervention (OR=6.28; 95% CI=1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR=7.51; 95% CI=4.37-12.91), respiratory tract viral infection (OR=7.75; 95% CI=1.60-37.57), cytomegalovirus infection or disease (OR=2.67; 95% CI=1.12-6.32), and acute graft rejection (OR=3.01; 95% CI=1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR=0.65; 95% CI=0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.