Outcome Of Invasive Pulmonary Aspergillosis Research Articles

Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study

RationaleThe prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests.ObjectivesTo identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs).MethodsWe conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria.Measurements and main resultsOf the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality.ConclusionsAn aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

(742) - Contemporary Incidence and Outcomes of Invasive Pulmonary Aspergillosis in Heart Transplant Recipients

(742) - Contemporary Incidence and Outcomes of Invasive Pulmonary Aspergillosis in Heart Transplant Recipients

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

852. Epidemiology, clinical characteristics and outcomes of invasive pulmonary aspergillosis among critically ill patients in medical intensive care unit: A retrospective study from the tertiary care hospital in Thailand

Abstract Background Invasive pulmonary aspergillosis (IPA) is a serious infection which leads to poor outcomes particularly in immunocompromised patients. Recently, IPA in critically ill patients in intensive care unit (ICU) has been increasingly recognized owing to its substantial morbidity and mortality. However, clinical data of IPA in ICU is scarce especially in Thailand. Methods A single-center, retrospective, observational study was conducted in King Chulalongkorn Memorial Hospital. We collected data on demographic, clinical characteristics, and outcomes of the patients who developed IPA during admission in the medical intensive care unit (MICU) between Jan 2016 to Dec 2021. IPA was identified by using ICD-10 and medication code for voriconazole, amphotericin B or liposomal amphotericin B. Patients met proven, probable IPA according to EORTC/MSG definition or putative IPA were included. The primary outcome was the incidence of IA in the MICU. Clinical characteristics, 12-week all-cause mortality and associated risk factor were the secondary outcomes. Results During the study period, a total of 5,019 patients were admitted in MICU. Fifty-seven met definitions of IPA which represented incidence of 1.14%. Seven patients (12.3%) had proven IPA, while 37 (61.4%) and 13 (22.8%) patients had probable and putative IPA, respectively. Cardiovascular disease (33.3%), chronic liver disease (26.7%), and diabetes (20.0%) were common comorbidities in patients with putative IPA. Diagnosis was made at median of 5 (3-10) days after ICU admission. Organisms were identified in 36 patients (63%) which Aspergillus fumigatus was the most common species (36.8%). All-cause mortality at week 12 was 89.5%. SOFA score (OR 1.494, 95%CI 1.058-2.110) and vasopressor used on admission (OR 16.00, 95%CI 2.209-115.92) had trend toward increase mortality. Median survival in putative and probable IPA group were 4 and 8 days after diagnosis (p= 0.023). Patients who received treatment with voriconazole had median survival 13 days compared to 5 days in other antifungal agents (p= 0.006). Conclusion IPA carried a high mortality among critically ill patients in MICU. High SOFA score and vasopressors used at the MICU admission were associated with mortality. Voriconazole therapy appeared to correlate with longer survival time. Disclosures All Authors: No reported disclosures

Invasive pulmonary aspergillosis in critically ill patients with pneumonia due to COVID-19, influenza, and community-acquired pneumonia: A prospective observational study.

Influenza A and SARS-CoV-2 are risk factors for invasive pulmonary aspergillosis. Both influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis result in high mortality and poor clinical outcomes. No prospective study has so far compared the features, treatment, and outcomes of influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis within a similar time frame. Therefore, this study aimed to determine the frequency, risk factors, and outcomes of invasive pulmonary aspergillosis in critically ill patients with influenza, COVID-19, and community-acquired pneumonia. This prospective study included adult patients with pneumonia and was conducted at The Aga Khan University Hospital in Karachi, Pakistan. Patients were divided into three groups, including community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia. The data collected included information on demographic characteristics, comorbidities, clinical features, laboratory results, treatment, and outcomes. A total of 140 patients were included in this study. These included 35 (25%), 70 (50%), and 35 (25%) patients with community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia, respectively. In addition, 20 (14.2%) patients were found to have invasive aspergillosis, of whom 10/35 (28.5%), 9/70 (12.8%), and 1/35 (2.8%) patients were in the COVID-19, influenza, and community-acquired pneumonia groups, respectively. Moreover, nine (90%) COVID-19-associated pulmonary aspergillosis patients required vasopressors, compared to three (33%) patients with influenza-associated pulmonary aspergillosis (P=0.020). In total, seven (70%) COVID-19-associated pulmonary aspergillosis patients required invasive mechanical ventilation compared to four (44%) influenza-associated pulmonary aspergillosis patients (P=0.37). The mean±SD length of hospital stay was highest in the COVID-19-associated pulmonary aspergillosis patients (18.3±7.28 days) compared to influenza-associated pulmonary aspergillosis patients (11.7±5.34 days) (P=0.036). The number of deaths in influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis patients was three (33.3%) and five (50%), respectively (P=0.526). A higher proportion of patients with COVID-19 developed invasive aspergillosis compared to those with influenza. Although the mortality rate in COVID-19-associated pulmonary aspergillosis was comparable to that in influenza-associated pulmonary aspergillosis patients, COVID-19-associated pulmonary aspergillosis patients had a significantly longer stay in the hospital.

Outcomes of invasive pulmonary aspergillosis in hospitalized hematopoietic stem cell transplantation recipients: A National Readmission Database study.

e19051 Background: Hematopoietic Stem Cell Transplant (HSCT) is well established method of treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with compromise in the host immune system and increases risk of various infection in these patients, such as Invasive Pulmonary Aspergillosis (IPA). Methods: A retrospective study of a nationally representative cohort of hospital admissions was conducted from January 1, 2013 to December 31, 2018. Data was collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) Nationwide Readmissions Database (NRD) between 2013 and 2018. We used the International Classification of Diseases, 10th revision (ICD–10), and 9th revision (ICD-9) diagnostic codes to identify patients with IPA and HSCT. All adult patients ≥18 years were included in the study. Our study's primary objective was to assess the relationship between IPA on in-hospital mortality and 30-day readmission among patients undergoing HSCT. A secondary objective was to examine potential differences in complications between HSCT with IPA and HSCT without IPA. The absolute yearly mortality and rate of IPA for HSCT patients from 2013 to 2018 were also calculated. We used survey statistics to calculate weighted analysis and compared with Pearson’s chi-square test for categorical variables and t-test for the continuous variables. We calculated the odds ratio and 95% confidence interval in multivariate logistic regression for association of mortality among patients with IPA adjusted for model 1 variables including age, sex, smoking status, insurance type, and comorbid conditions. All p-values were 2 sided, with a significance threshold of p < 0.05. Results: A total of 90,451 index hospitalizations for HSCT were identified for the years 2013-2018 in the NRD with the 89,331 index hospitalizations for HSCT without IPA, and 1,092 index hospitalizations for HSCT-IPA. The in-hospital mortality for HSCT-IPA was higher as compared to HSCT without IPA (18.3% vs 4.2%; p < 0.001). HSCT-IPA had a significantly higher 30-day readmission rate (36.2%) than HSCT without IPA (24.0%). The HSCT-IPA group had higher multi-organ complications including atrial fibrillation (AF) (13.6% vs 8.3%; p < 0.007), acute kidney injury (AKI) (54.8% vs 22.0%; p < 0.001), respiratory failure (51.3% vs 13.5%, p < 0.001), pneumonia (65.4% vs 19.4%, p < 0.001), sepsis (38.2% vs 18.5%, p-value < 0.001), septic shock (16.1% vs 5.1%, p < 0.001), need for mechanical ventilation (21.1% vs 5.1% p < 0.001), non-invasive positive pressure ventilation (4.9% vs 2.5%, p < 0.001), and intensive-care unit admission (21.8% vs 6.1% p < 0.001). Conclusions: IPA is rare but fatal complication associated with HSCT with higher in-hospital mortality, 30-day readmission, and complications due to multiorgan failure.

Malignant course of invasive pulmonary aspergillosis in the new coronavirus infection COVID-19

Respiratory infections caused by fungal pathogens are the main cause of death in immunocompromised patients. During the COVID-19 pandemic, the registration of respiratory fungal pathology, especially pulmonary aspergillosis, has increased significantly.
 We present a histopathologically confirmed case of fatal invasive pulmonary aspergillosis complicating COVID-19. A 65-year-old patient with long-term diabetes backgrounded with a severe course of COVID-19 (the virus was identified ICD-10 code U07.1) described. During the illness bilateral polysegmental pneumonia of fungal-bacterial (Klebsiella pneumoniae) etiology with necrosis and sequestration of the affected tissue the lower lobe of the right lung with the formation of a fungal ball and the development of a right-sided pneumothorax was developed. In other parts of both lungs, focal destruction of the interalveolar septa was determined with the formation of small cavities filled with detritus and accumulations of segmented neutrophils, with the proliferation of fungal mycelium, positively stained in the PAS reaction. Fungal hyphae and conidial heads were also found in the lumens of individual bronchi and vessels with invasion of their walls. Long-term (more than one month) course of the disease, clinical and radiological dynamics, and detection of a forming connective tissue capsule along the periphery of the necrosis zone during microscopy testifies in favor of the subacute nature of the infection.
 The presented clinical case, as well as a review of current publications and meta-analyses on invasive pulmonary aspergillosis, point to diagnostic problems and poor outcomes of invasive pulmonary aspergillosis in patients with COVID-19.
 Pulmonary aspergillosis associated with COVID-19 is a serious and potentially life ― threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment. Early diagnosis of fungal infections is crucial to ensure the survival of such patients. Targeted biopsy examination with microscopy and/or seeding of a lung biopsy allows not only to establish the diagnosis of aspergillosis, but also to determine the presence of tissue invasion.
 Further research should include approaches aimed at developing an effective diagnosis of fungal tissue invasion and respiratory tract damage, determining the patients immune status in order to conduct personalized immunotherapy.

Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave.

Background: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. Methods: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. Results: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients’ characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4–7.4] p = 0.005). Conclusion: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.

Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta-analysis.

BackgroundAn increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta‐analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza.MethodsA systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random‐effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed.ResultsFourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non‐European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy.ConclusionsThe IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high‐risk factors, should be thoroughly screened for IPA.

987. Clinical Epidemiology and Outcomes of Invasive Pulmonary Aspergillosis as a Complication of Respiratory Viral Infection in Hospitalized Patients

BackgroundInvasive pulmonary aspergillosis (IPA) is increasingly recognized as a complication of severe respiratory viral infections (RVIs), including influenza and COVID-19. However, the incidence and outcomes of IPA following other RVIs is not well-described. We hypothesized that IPA may be an underreported complication of non-influenza RVIs. The objective of this study was to quantify the incidence and associated outcomes of IPA following RVI in hospitalized patients.MethodsWe conducted a single-center retrospective cohort study of adult hospitalized patients with RVI diagnosed by multiplex PCR-based assay at the University of Kansas Hospital (Kansas City, Kansas) from September 2018-October 2019. Patients with a diagnosis of proven or probable IPA prior to RVI and those with hospital admission < 24 h were excluded from analysis. Proven or probable IPA was defined according to EORTC/MSGERC consensus definitions. The primary outcome was 1-year all-cause mortality.ResultsA total of 195 patients met study criteria and were included in the analysis. The most common types of RVI observed were rhinovirus/enterovirus (57.9%, n=113), parainfluenza (13.3%, n=26), influenza (8.2%, n=16), and respiratory syncytial virus (7.7%, n=15). The cumulative incidence of IPA infection within 6 weeks of RVI was 5.6% (n=11). Excluding patients co-infected with multiple respiratory viruses (n=5), IPA was numerically more likely to occur following influenza compared to non-influenza RVI (12.5% [ n=2/16] vs. 4.6% [n=8/174]; odds ratio, 2.96; 95% confidence interval [CI], 0.57-15.3; P=0.176). Overall, one-year all-cause mortality was 20% (n=39/195) in this cohort. Development of IPA as a complication of RVI was associated with a significant decrease in 1-year survival (hazard ratio [HR], 3.04; 95% CI, 1.19-7.78; P=0.021), and this relationship persisted after adjustment for age (HR, 2.77; 95% CI, 1.08-7.10; P=0.034). ConclusionIn a cohort of hospitalized patients with RVI, 5.6% of patients developed proven or probable IPA. Although IPA was more likely to occur in patients with influenza, this complication was also observed with other types of RVI. Invasive pulmonary aspergillosis may be an underappreciated complication of non-influenza RVI in hospitalized patients and warrants continued study.Disclosures All Authors: No reported disclosures

Risk factors for development and mortality of invasive pulmonary Aspergillosis in kidney transplantation recipients.

Invasive pulmonary aspergillosis (IPA) is a high mortality opportunistic infection among kidney transplant recipients. This study assessed the risk factors and outcomes of IPA after KT. A retrospective study was conducted at a tertiary-care referral hospital in Korea. Electronic medical records of patients diagnosed with IPA after KT between February 1995 and March 2015 were reviewed. The control patients comprised two patients who received KT before and after each IPA case. Twenty-six cases were diagnosed with IPA among 1963 recipients at a median of 58years old. The most common cause of end-stage renal disease was diabetic nephropathy. The median time to diagnosis was 161days. Delayed graft function was associated with the development of IPA. The overall 12-week mortality rate of IPA was 57.5%. Serum GM level ≥ 2 and BAL GM level ≥ 5 were associated with 12-week mortality in the Kaplan-Meier survival analyses. Approximately half of IPA in KT recipients developed during the late posttransplant period (> 6months), especially after treatment for acute rejection. Careful monitoring for IPA is required in patients with delayed graft function, DM, and who received rejection therapy. Higher serum and BAL GM were associated with 12-week mortality.

Invasive Pulmonary Aspergillosis in Adults With Avian Influenza A (H7N9) Pneumonia in China: A Retrospective Study.

Cases of severe influenza with Aspergillus infection are commonly reported in patients with severe influenza. However, the epidemiology, risk factors, and outcomes of invasive pulmonary aspergillosis (IPA) in patients with avian influenza A (H7N9) infection remain unclear. We performed a retrospective multicenter cohort study. Data were collected from patients with avian influenza A (H7N9) infection admitted to 17 hospitals across China from February 2013 through February 2018. We found that IPA was diagnosed in 18 (5.4%) of 335 patients; 61.1% of patients with IPA (11 of 18) were identified before or within 2 days after an H7N9 virus-negative result. The median hospital stays in patients with or without IPA were 23.5 and 18 days, respectively (P < .01), and the median intensive care unit stays, respectively, were 22 and 12 days (P < .01). Smoking in the past year and antibiotic use for >7 days before admission were independently associated with IPA (adjusted odds ratio [95% confidence interval], 6.2 [1.7-26] for smoking and 4.89 [1.0-89] for antibiotic use). These findings provided important insights into the epidemiology and outcomes of IPA in patients with H7N9 infection in China.

Comparison of Clinical Manifestation, Diagnosis, and Outcomes of Invasive Pulmonary Aspergillosis and Pulmonary Mucormycosis.

Objects: Invasive pulmonary mold infection usually has devastating outcomes. Timely differentiation between invasive pulmonary aspergillosis (IPA) from pulmonary mucormycosis (PM) is critical for treatment decision-making. However, information on IPA and PM differentiation is limited. Methods: We conducted a retrospective, multicenter, observational study, with proven and probable IPA and PM patients from January 2004 to December 2017. Demographics, clinical manifestations, image reports, histopathological findings, and outcomes were analyzed. Results: A total of 46 IPA (33 proven and 13 probable) and 19 PM (18 proven and one probable) cases were analyzed. The majority of tissues (81% in IPA and 61% in PM) were obtained using bronchoscopy. Prior influenza infection was a predisposing factor for IPA, and abscess formation in CT scan was associated with PM (p = 0.0491, p = 0.0454, respectively). The positive culture rate for PM was lower than that for IPA (37% vs. 67%, p = 0.0294). The galactomannan (GM) level from serum and bronchoalveolar lavage (BAL) fluid was significantly higher in IPA than in PM (3.3 ± 0.5 vs. 0.8 ± 0.6, p = 0.0361; 4.0 ± 0.6 vs. 0.59 ± 0.1, p = 0.0473, respectively). The overall mortality rate was 65%, which was similar among IPA and PM groups. Systemic steroid exposure and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were independently correlated to mortality in IPA (p = 0.027, p = 0.026, respectively). However, there was no predictor for mortality found in PM patients. Conclusions: Influenza infection, abscess formation in CT scan, and GM level may help physicians to differentiate IPA and PM. Bronchoscopy-guided biopsy and lavage specimen provide timely and definite diagnosis. The prognosis of IPA is associated with systemic steroid exposure and higher APACHE II scores on admission.

Prevalence and outcome of invasive pulmonary aspergillosis in critically ill patients with liver cirrhosis: an observational study

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in critically ill patients with endstage liver disease. Therefore, aim of this study is to predict the prevalence and outcome of IPA in critically ill patients with underlying liver cirrhosis and evaluation of the necessity Glactomannan (GM) screening in serum and bronchoalveolar lavage (BAL) in this cohort. In total 12 out of 84 patients (14%) had probable IPA. The mean optical density index (ODI) bronchoalveolar lavage (BAL) GM index was 3.6 ± 1.5 (Range: 1.7–5.7). An overall sensitivity of 90% (95% CI 86–96%) and specificity of 85% (95% CI 81–88%) was found for the BAL GM in IPA. Acute Physiology And Chronic Health Evaluation (APACHE II), sequential organ failure assessment (SOFA) as well the model of endstage liver disease (MELD) score were significantly higher in the probable IPA group as compared to the No IPA group (26 versus 21, p < 0.001 and 14 versus 10, p < 0.044). Length of intensive care unit (ICU) stay was significantly longer in probable IPA patients (16 versus 10 days, p < 0.027) and mortality rate was significantly higher in probable IPA patients (100% versus 65%, p < 0.001) as compared to No IPA patients. APACHE II and MELD score were independently associated with higher mortality rate using multivariate logistic regression (p = 0.025 and p = 0.034). In conclusion, IPA has a relevant impact on outcome. Screening for IPA is indicated, easy to perform and a necessity to improve outcome.

Hypoxia attenuates anti‐Aspergillus fumigatus immune responses initiated by human dendritic cells

Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A.fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated invitro with germ tubes of A.fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A.fumigatus. These data suggest that hypoxia at the site of A.fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients.

Combination Therapy for Invasive Aspergillosis: Controversies and Conclusions

Historically poor outcomes have generated many efforts toward improving outcomes of invasive pulmonary aspergillosis in immunosuppressed hosts, by improving prevention strategies, use of early diagnostics, and employing new antifungals, including combinations of drugs. The latter approach is supported by theoretical benefits in both the antimicrobial activity and pharmacologic properties of drugs, with in vitro and animal studies suggesting potential utility. Because drug combinations can also increase toxicities, interactions, and costs, demonstrating therapeutic effects in clinical trials is imperative. Here, clinical data evaluating combination antifungal therapy for aspergillosis are reviewed. Results to date suggest potential benefit of antifungal combinations, especially those including azoles and echinocandins, but conclusions are not definitive. This important topic warrants further study.

Invasive Aspergillus infections in hospitalized patients with chronic lung disease

BackgroundAlthough invasive pulmonary aspergillosis (IPA) is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.MethodsThe records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.ResultsBaseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61%) and asthma (18%), and immunocompromised patients primarily had malignancies (27%) and bone marrow transplants (14%). A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03). The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14); 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75).ConclusionNontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the more traditional immunocompromised population.

Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content. In addition, hypoxia-induced cell wall alterations increase macrophage and neutrophil responsiveness and antifungal activity as judged by inflammatory cytokine production and ability to induce hyphal damage. We observe that these effects are largely dependent on the mammalian β-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus β-glucan exposure correlates with the presence of hypoxia in situ. Our data suggest that hypoxia-induced fungal cell wall changes influence the activation of innate effector cells at sites of hyphal tissue invasion, which has potential implications for therapeutic outcomes of invasive pulmonary aspergillosis.

Epidemiology and Clinical outcomes of Invasive Pulmonary Aspergillosis: A Nationwide Multicenter Study in Korea

Epidemiology and Clinical outcomes of Invasive Pulmonary Aspergillosis: A Nationwide Multicenter Study in Korea

Prospective Evaluation of Clinical and Biological Markers To Predict the Outcome of Invasive Pulmonary Aspergillosis in Hematological Patients

Early evaluation of treatment efficacy in invasive aspergillosis (IA), a leading cause of morbidity and mortality in hematological patients, remains a challenge. We conducted a prospective study to evaluate the performance of different markers in predicting the outcome of patients with IA. Both clinical and biological criteria were assessed 7, 14, 21, and 45 days after inclusion in the study, and mortality was assessed at day 60. The association between baseline data and their evolution and the day 45 response to treatment was analyzed. A total of 57 patients (4 with proven, 44 with probable, and 9 with possible aspergillosis according to the revised EORTC/MSG [European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group] definitions) were included. At day 45, 30 patients (53%) were determined to be responders, 25 (44%) were nonresponders, and 2 were not able to be evaluated. Twenty patients died within the 60 days of follow-up. We found that a poor day 45 outcome was associated with patients who had high baseline serum galactomannan (GM) antigen levels and those receiving steroids at the time of IA. A consistently negative serum GM index was associated with a good outcome, and the day 14 clinical evaluation was predictive of the day 45 outcome. No association was found between Aspergillus antibodies or DNA detection and patients' outcome. We conclude that the GM index value at diagnosis of IA, GM index kinetics, and clinical evaluation at day 14 are good markers for predicting the outcome of patients with IA and should be taken into account for adapting antifungal treatment.