Positive Galactomannan Research Articles

2114. Invasive fusariosis in the era of mold active azoles and molecular targeted chemotherapy: Increasing incidence and lack of improved outcomes

Abstract Background Invasive fusariosis (IF) is an uncommon opportunistic mold infection primarily affecting patients (pts) with leukemia and allogeneic hematopoietic cell transplant (HSCT). Historically, IF had poor outcome when there is lack of recovery from immunosuppression. However, IF incidence and outcome in the in the era of new mold-active triazoles and leukemia regimens that incorporate molecularly targeted drugs is unknown. Methods We retrospectively studied the incidence, risk factors, clinical features, and outcome of microbiologically documented IF (revised EORTC/MSG criteria) in pts with leukemia at MD Anderson Cancer Center in the last 12 years (June 2009-October 2021). The independent risk factors for 42-day (d) mortality from IF diagnosis were assessed by a binary multivariable logistic regression model. Annual incidence density (1998-2021) was estimated using Poisson regression analysis. Results Among 140 IF pts (114 proven, 26 probable), 100 (71%) had pneumonia, 88 (63%) disseminated infection, and 32 (23%) sinusitis, with no apparent changes in relative frequency over the years. 124 pts (89%) had neutropenia (ANC < 500) at IF diagnosis, 118 (84%) had relapsed/refractory (R/R) leukemia, and 43 (31%) had prior HSCT. 19% (18/97 pts) of IF pts had positive serum galactomannan and 55% had coinfections. In the last 5 years of the study, 45/58 IF cases (78%) were breakthrough infections to mold active triazoles (12 voriconazole, 25 posaconazole, 8 isavuconazole). 74 (53%) out of the 140 IF pts died by d42. Only 6 pts (9%) had neutrophil recovery at time of death compared to 47 (64%) who survived until day 42 (P < 0.001). Neutrophil recovery (aOR 0.04, 95% CI 0.01-0.14), SOFA score (aOR 1.91 per point, 95% CI 1.47-2.50), and pneumonia (aOR 3.28, 95% CI 1.11-9.70) were independent predictors of 42-d mortality. Since 1998, the incidence density of IF continuously increased (P = 0.006) at an annual ratio of 1.05 (95% CI 1.02-1.07, Figure 1). Figure 1Incidence density of invasive fusariosis (per 100,000 patient-days) in leukemia patients between 1998 and 2021 Conclusion Over the past 23 years, IF incidence has been increasing. IF is predominantly seen in pts with R/R acute leukemia and increasingly seen as a breakthrough infection to mold-active triazoles. Even in contemporary pt cohorts, IF has high mortality in the setting of persistent myelosuppression. Disclosures Russell E. Lewis, PharmD, Air: Advisor/Consultant|Cidara: Advisor/Consultant|F2G: Advisor/Consultant|Gilead: Advisor/Consultant|Merck & Co, Inc: Grant/Research Support|Synexis: Advisor/Consultant Dimiitrios P. Kontoyiannis, MD, ScD, PhD (hon), AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant.

Blood Mucorales PCR to track down Aspergillus and Mucorales co-infections in at-risk hematology patients: A case-control study.

Serum Mucorales PCR can precede the final diagnosis of invasive mucormycosis by several days or weeks and could therefore be useful as a non-invasive screening tool. We assessed the performance of a commercial Mucorales PCR assay (MucorGenius®, PathoNostics, Maastricht, The Netherlands) on prospectively collected banked sera from hematology patients at risk for invasive mould infections. We evaluated if there is an underestimated incidence of missed Mucorales co-infections in patients with invasive aspergillosis (IA). We tested Mucorales PCR on the sera of all patients with a diagnosis of at least possible IA (EORTC-MSGERC consensus criteria) before the start of any antifungal therapy, and in a control group of similar high-risk hematology patients without IA (in a 1:4 ratio). When a positive Mucorales PCR was observed, at least 5 serum samples taken before and after the positive one were selected. Mucorales PCR was performed in 46 diagnostic serum samples of cases and in 184 controls. Serum Mucorales PCR was positive in 4 cases of IA (8.7%; 12.9% of probable cases) and in 1 control case (0.5%) (p=0.0061, OR=17.43 (1.90-159.96). Post-mortem cultures of the positive control became positive for Rhizopus arrhizus. Mortality of IA cases with and without a positive Mucorales PCR was not significantly different. Only in the PCR positive control case, serial serum samples before and after the diagnostic sample were also positive. It is not entirely clear what a positive Mucorales PCR in these cases implies since the 4 Mucorales PCR positive cases were treated with antifungals with activity against Mucorales. In addition, PCR was positive only once. This study does not provide enough evidence to implement Mucorales PCR screening. However, our findings emphasize once more the importance of considering the possibility of dual mould infections, even in patients with a positive galactomannan detection.

Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study.

The utility of surveillance bronchoscopy (SB) for the clinical management of lung transplant recipients (LTRs) is undefined. This study evaluates the role of SB in the monitoring and care of LTRs. We retrospectively analyzed all LTRs who had SB at Henry Ford Hospital in Detroit, Michigan between August 2014 and August 2019. Bronchoscopies performed for clinical symptoms, new radiographic abnormalities, and to assess stents or acute rejection were excluded. A total of 107 LTRs and 449 bronchoscopies were analyzed. The primary outcome was the rate of change in clinical care based on microbiologic and pathologic test results. Secondary outcomes were rates of microbiologic and pathologic test positivity and rates of adverse effects. The most common microbiologic tests performed on bronchoalveolar lavage were bacterial (96.9%), fungal (95.3%), and acid-fast bacillus (95.1%) stains and cultures. Of 2560 microbiologic tests, 22.0% were positive and resulted in therapy changes for 2.9%. Positive galactomannan, acid-fast bacillus tests, and Pneumocystis jirovecii antigen/polymerase chain reaction did not result in therapy changes. Of the 370 transbronchial biopsies performed, 82.2% were negative for acute rejection and 13% were positive for A1/A2 rejection. Immunosuppressive therapy changes occurred after 15.8% with reduction in immunosuppression due to positive microbiologic tests in 16.9%. Adverse events occurred in 8.0% of patients. Diagnostic stewardship is warranted when performing SB in LTRs.

Active screening of COVID-19-associated pulmonary aspergillosis with serum beta-glucan and endotracheal aspirates galactomannan and fungal culture.

Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution. To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol. We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM. A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p= .0004). Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.

Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Cellular Therapies: A Real-World Analysis

Objective: Cellular therapies, including CAR-T cell, gene therapy, autologous and allogeneic hematopoietic cell transplantation (HCT), remain a cornerstone in management of various benign and malignant disorders. Despite intensified efforts to improve strategies, invasive fungal infections (IFD) remain an important cause of morbidity and mortality. Therefore, we investigated risk factors, prevalence, and outcome of IFD in the era of novel anti-fungal prophylaxis. Methods: We retrospectively enrolled consecutive adult patients that underwent cellular therapies at our JACIE-accredited center according to standard operating procedures (2013-2022). We defined IFD according to current consensus (2020) and guidance on imaging (2021, EORTC). We analyzed the following factors: age, disease, donor, HLA matching, conditioning, graft, severe acute and moderate/severe chronic GVHD, antifungal prophylaxis, immunosuppressants, IFD type (according to current consensus), galactomannan/β-D-glucan, cultures, imaging, bacterial/viral infections, IFD treatment, relapse, and overall survival (OS). Results: We studied 950 recipients of cellular therapies (19 CAR-T cell and 2 gene therapies, 456 autologous and 473 allogeneic HCT). No CAR-T cell and gene therapy patient developed IFD; while 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Further analysis was performed only in allogeneic HCT recipients. Possible IFD was documented in 31/473 at a median of 112 (range 7-1353) post-transplant day, probable in 11/473 (5: positive galactomannan, 6: positive cultures) at 154 (12-469), proven in 10/473 (3: positive galactomannan, 7: positive cultures) at 226 (25-1146) day. Concurrence of bacterial or viral infection was documented in 20/52 and 17/52 patients respectively. Second IFD episode occurred in 3 patients (1: probable, 2: proven IFD), that succumbed to TRM (1) and relapse (2). Candida species were isolated in 9 patients, Fusarium in 2 and Aspergillus in 2. Mucormycosis was diagnosed in 2 patients, while the remaining IFD were attributed to aspergillosis. During the aplastic period, caspofungin had been administered as primary prophylaxis (41/52) and amphotericin as secondary prophylaxis (11/52), which were then changed to posaconazole and isavuconazole respectively for the immunosuppression period. Independent risk factors for IFD were type of donor (20% in alternative, 12% in unrelated, and 5% in sibling donors, p=0.006) and moderate/severe chronic GVHD (15% versus 8%, p=0.029). Five-year OS was significantly lower in patients with IFD, especially those with proven IFD (p=0.041). IFD remained a predictor of OS (p=0.044) independently of donor type and chronic GVHD. Conclusions: Our large real-world cohort indicates the relatively low prevalence of proven IFD in the era of novel antifungal prophylaxis, which is however associated with poor outcomes in allogeneic HCT recipients. Possible IFD, assessed by host and clinical factors including updated documentation of imaging, has shown similar outcomes to probable IFD. Therefore, wider application of sensitive mycological testing is needed for high-risk populations, such as alternative alloHCT recipients or chronic GVHD patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P155 A Mexican case series of COVID-19 - associated pulmonary aspergillosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMThe pandemic coronavirus disease 2019 (COVID-19) has been in the scope for invasive pulmonary aspergillosis (IPA) after the first reports worldwide, now known as CAPA.Objectiveto describe a case series of CAPA documented in four intensive care units while treating patients with severe COVID-19 pneumonia in order to describe clinical characteristics, cultures result and MICs from Aspergillus isolations, and treatments.MethodsA prospective and descriptive study was performed from March 2020 to February 2022 in four tertiary level hospitals that treated COVID-19 patients in Mexico. We followed every single culture coming from the COVID-19 ICU, Aspergillus positive cultures had morphologic identification, and the MICs were obtained by broth microdilution. We did not interfere in the treatment.ResultsDuring 24 months of follow-up of patients with severe COVID-19 we found 17 adult cases with a mold identification, from those, 14 patients fit in the possible CAPA definition according to ECMM/ISHAM, and the remaining 3 were treated after expert opinion. The baseline characteristics of overall 47% had diabetes, and 41% were obese. Of the 14 cases included as a possible CAPA all of them had acute severe respiratory syndrome (average PaO2/FiO2 134 mmHg), 64% were in prone position, 78% had steroids at ICU admission, 92% had antibiotics at ICU. The computed tomography pattern predominantly associated were pulmonary infiltrates, nodules and cavitation. Only 2 patients (14%) had a positive galactomannan (>4.5) from non-bronchoscopic lavage. We had 9 Aspergillus fumigatus isolations and 4 A. niger, 1 A. flavus, 6 patients received voriconazole, 3 patients received isavuconazole, 1 anidulafungin and liposomal amphotericin B were used in 1 patient each respectively. The predominant MIC from isolations were ≥64 μg/ml for fluconazole, and <0.5 μg/ml for voriconazole, also all of them had MIC equal or <0.75 μg/ml for isavuconazole and 0.015 μg/ml for anidulafungin. A total of 50% of the patients had a CAPA-related death.ConclusionsCAPA is still a difficult entity to think of for diagnosis and treatment in severely ill COVID-19 patients. What predominates like other series were obesity, use of steroids, and ARDS. The contribution of small Mexican series like ours (based on the new guidelines) will allow to understand that CAPA could be no longer a rare fungal infectious disease complication in severely ill COVID-19 patients. An extended consensus must be made for those possible CAPA definition cases.

P169 Systemic Pythiosis: presumably, the first human case in India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesThis is the first human case of systemic disease due to Pythium insidiosum reported from India. The case highlights difficulty in diagnosis and management.MethodsA 44-year-old male patient had a peri-esophageal and peri-gastric inflammatory lesion which showed inflammation along with sparsely septate hyphae (Fig. 1), and partially responded to voriconazole (VCZ). After 1.5 years, he developed a massive liver lesion (Fig. 2), and hepatic venous thrombosis which was refractory despite restarting therapy with posaconazole (PCZ). As a desperate measure, surgical excision of the large liver lesion was undertaken.ResultsSerum BDG was positive and Serum Galactomannan was negative. There was no tidy explanation for the insidious clinical course of the illness over 1.5 years, partial response to VCZ for the esophageal lesion and inadequate response of the subsequent lesion to PCZ. The liver biopsy specimen showed a flat, feathery growth on SDA which was identified at PGI, Chandigarh by ITS as P. insidiosum. P. insidiosum and additionally Rhizopus microsporus were identified by molecular sequencing from the surgical specimen as well. The patient succumbed to carbapenem-resistant Klebsiella bacteremia in the postoperative stage.ConclusionThe case underscores the insidious course of systemic pythiosis, diagnostic, and management challenges.

P203 Chronic pulmonary aspergillosis (CPA) in post tuberculosis sequele— aclinical experience from tertiary care

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMIntroductionChronic pulmonary aspergillosis (CPA) is a spectrum of illnesses clinically presenting as a persistent cough, dyspnea, hemoptysis, fatigue, and weight loss and radiologically can range from single aspergilloma, Aspergillus nodule, or chronic cavitary pulmonary aspergillosis (CCPA) which can progress to chronic fibrosing pulmonary aspergillosis if left untreated.1 CPA has high morbidity, burden in India estimated to be in a 5-year prevalence of 24/100 000.2 The commonly used criteria for diagnosing CPA include cough or hemoptysis for 1 month, raised Aspergillus-specific IgG, absence of positive GeneXpert test for Mycobacterium tuberculosis and either paracavitary fibrosis or a fungal ball on imaging of the thorax or progressive cavitation (either new cavitation or deterioration of pre-existing cavitation) on serial chest radiographs. Pulmonary tuberculosis (PTB) is the important predisposing risk factor for CPA,3 India being an endemic country, incidence of CPA may be underestimated or it may be misdiagnosed as smear-negative tuberculosis. Microbiologically, diagnosis by direct confirmation of Aspergillus spp infection (microscopy or culture from respiratory samples) may not be always positive, in such a scenario the immune response to Aspergillus spp. by measuring Aspergillus specific Immunoglobulin Ig G in clinically suspected cases may be used for diagnosis of CPA.MethodThis is a cross-sectional conducted in a tertiary care hospital, New Delhi, India. The patients with previous history of pulmonary tuberculosis who presented with symptoms of cough, hemoptysis, fever, shortness of breath, chest pain, and weight loss of ˃12-week duration were enrolled in the study. Relevant investigations including blood tests, chest imaging, sputum examination for bacterial infections, fungal (KOH mount), and tuberculosis (AFB smear, CBNAAT, mycobacterial cultures) were done. Microbiological evidence included a positive Aspergillus-specific IgG (cut off >8 units/ml) or positive serum galactomannan index (GMI) (cut off >1 according to EORTC/MSG guidelines) or KOH mount on sputum showing branching hyaline septate hyphae morphologically suggestive of Aspergillus spp. Patients who were diagnosed with CPA according to criteria were treated and followed up.ResultsA total of 15 patients were screened in the study, 4 patients who had concurrently detected pulmonary tuberculosis detected by Genexpert, were excluded from the study. Majority of patients presented with complaints of recurrent episodes of cough and hemoptysis. Imaging features included cavitation, bronchiectasis, pleural thickening, and fungal ball. Sputum microscopy for fungal elements was positive only in 10 patients. The serum Aspergillus Ig G (values ranged from 19.8-200 u/mL) was raised in all patients while serum GMI above cut-off was present in only 5 patients. All confirmed CPA patients were managed with voriconazole for 4 months. Following 4 months of treatment, all patients had favorable outcomes in terms of radiological improvement and clinical cure.ConclusionCPA is an underestimated post-PTB sequel and should be considered as differentials in patients with respiratory symptoms in post TB patients. Aspergillus Ig G and chest imaging are recommended as initial diagnostic tools for diagnosing CPA.Sources:Denning DW, Cadranel J, Beigelman-Aubry C et al. European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016; 47(1): 45-68.Agarwal R, Denning DW, Chakrabarti A. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS One. 2014; 9(12): e114745.Page ID, Byanyima R, Hosmane S et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. Eur Respir J. 2019; 53: 1801184

Concordancia del antígeno de galactomanano en lavado broncoalveolar broncoscópico y mini lavado broncoalveolar a ciegas

Introduction: viral pneumonias increase the susceptibility to develop fungal secondary infections. With COVID-19 pandemic, multiple cases of invasive pulmonary aspergillosis associated with COVID-19 (PAAC) have been reported, increasing mortality. It is not recommended to perform bronchoscopy during COVID-19 illness given the risk of aerosolization, so new techniques such as mini bronchoalveolar lavage (BAL) emerge. The necessity to perform a validating task for the galactomannan (GM) measurement in samples obtained through mini-BAL emerges from the absence of cutting points for the GM antigen positivity in respiratory samples non obtained by bronchoscopy.&nbsp; Aim: to validate the concordance of GM measurement in respiratory samples obtained through mini-BAL and BAL by bronchoscopy.&nbsp; Material and methods: observational and analytical prospective study. Patients admitted to intensive care unit with suspected PAAC who were asked to obtain respiratory samples for MG study were included. In all the cases, BAL and mini-BAL samples were obtained in one same procedure. It was considered positive GM with a value higher than 1.&nbsp; Results: 11 patients were studied, 6 (54.5%) cases were diagnosed positive for PAAC through bronchoscopic BAL. The mini-BAL sensitivity was 33% and the specificity 100%; predictive positive value 100% and negative predictive value 55%. The concordance correlation coefficient was 0,28% (IC -0,078 a 0,57), which showed a poor concordance between both methods. Conclusion: The GM test through mini-BAL could prove to be a fine confirmatory method, while a negative result does not discard PAAC.

Serum Aspergillus-specific IgE, IgG and IgG4 immunoglobulins assessment in the work-up of invasive pulmonary aspergillosis: a prospective cohort study.

Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG<inf>4</inf>, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy). We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG<inf>4</inf> specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patients. Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG<inf>4</inf> showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM. In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

Predictors and outcomes of peritoneal dialysis-related infections due to filamentous molds (MycoPDICS).

We sought to evaluate the predictors and outcomes of mold peritonitis in patients with peritoneal dialysis (PD). This cohort study included PD patients from the MycoPDICS database who had fungal peritonitis between July 2015-June 2020. Patient outcomes were analyzed by Kaplan Meier curves and the Log-rank test. Multivariable Cox proportional hazards model regression was used to estimating associations between fungal types and patients' outcomes. The study included 304 fungal peritonitis episodes (yeasts n = 129, hyaline molds n = 122, non-hyaline molds n = 44, and mixed fungi n = 9) in 303 patients. Fungal infections were common during the wet season (p <0.001). Mold peritonitis was significantly more frequent in patients with higher hemoglobin levels, presentations with catheter problems, and positive galactomannan (a fungal cell wall component) tests. Patient survival rates were lowest for non-hyaline mold peritonitis. A higher hazard of death was significantly associated with leaving the catheter in-situ (adjusted hazard ratio [HR] = 6.15, 95%confidence interval [CI]: 2.86-13.23) or delaying catheter removal after the diagnosis of fungal peritonitis (HR = 1.56, 95%CI: 1.00-2.44), as well as not receiving antifungal treatment (HR = 2.23, 95%CI: 1.25-4.01) or receiving it for less than 2 weeks (HR = 2.13, 95%CI: 1.33-3.43). Each additional day of antifungal therapy beyond the minimum 14-day duration was associated with a 2% lower risk of death (HR = 0.98, 95%CI: 0.95-0.999). Non-hyaline-mold peritonitis had worse survival. Longer duration and higher daily dosage of antifungal treatment were associated with better survival. Deviations from the 2016 ISPD Peritonitis Guideline recommendations concerning treatment duration and catheter removal timing were independently associated with higher mortality.

Acute Abdominal Distention in a Premature Low-birthweight Infant.

Acute Abdominal Distention in a Premature Low-birthweight Infant.

Clinical, Laboratory, Radiological, Bronchoscopic, and Outcome Characteristics of Pulmonary Fungal Infection in Children in PICU in Central China: A Case Series.

ObjectiveFungal infections are common in pediatric intensive care units (PICUs), but the monitoring methods are limited. This study analyzed the differences in clinical features, diagnosis, and treatment between PICU patients with and without fungal infection.MethodsThis retrospective study analyzed PICU patients at the Maternal and Child Health Hospital of Hubei Province diagnosed with severe pneumonia between January 2015 and January 2020. The patients were divided into the fungal (F) and non-fungal (NF) infection groups. Levels of 1,3-beta-D-glucan (BDG) and galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) were analyzed. Chest computed tomography (CT) images were reviewed.ResultsA total of 357 patients were included. In the F group, fever, moist rales, coarse rales, shortness of breath, and sepsis were more common (all P < 0.05); PICU time, hospitalization duration, and BDG- and GM-positive rates in serum and BALF were all significantly higher than in the NF group (all P < 0.05). The BDG- and GM-positive rates in serum and BALF were higher in the F than in the NF group (all P < 0.05). The abnormal lymphocyte ratios in serum were higher in the F group (all P < 0.05). Wedge-shaped, patchy, streaky shadows and subpleural reticulation were higher in CT images of the F group (all P < 0.05). Tracheobronchial stenosis was more common in pulmonary fibroscopy results of the F group (P = 0.04).ConclusionPICU pneumonia patients with fungal infection have specific clinical and laboratory features compared with those without fungal infection, including higher rates of BALF, serum BDG, GM positivity and tracheobronchial stenosis.

Case report: Vascular graft infection due to Aspergillus species presenting with recurrent vascular occlusion

BackgroundAn aortic graft implantation is an effective therapeutic method for various aortic diseases. However, it is known that sometimes these implanted grafts can be the foci of infections. Here we report a rare case of graft infection that presented multiple embolisms of aortic branches and peripheral organs.Case presentationA 63-year-old Japanese woman with a history of aortic graft implantation presented with occlusions of large arteries in different loci and time points, with elevation of non-specific inflammatory markers. Thoracic contrast-computed tomography (CT) captured vegetation in the descending aortic graft and the [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) showed accumulation of FDG in the same site, suggesting a graft infection. Despite all these suspicious findings, repeated blood culture examinations never detected any microorganisms. A diagnosis of Aspergillus graft infection was made based on an elevated serum β-D glucan (βDG) and a positive Aspergillus galactomannan (GM) antigen test. The patient subsequently had surgery with replacement of the descending aortic graft and anti-fungal drugs were instituted with significant improvement noted.ConclusionIn the present case, the patient’s specific feature in the anatomical vascular construction, past operation, and basal fundamental diseases collaboratively contributed to the pathogenesis of the present infection. It is important to recognize the risk of graft infection and conduct imaging studies when indicative symptoms emerge. The negativity in blood culture studies often makes detection of pathogenic microbes extremely difficult. This case suggests that non-cultural tests such as bDG and GM can be useful for diagnosis and starting appropriate anti-fungal drugs in the early stages.

Characteristics and Outcomes of Patients with Invasive Pulmonary Aspergillosis and Respiratory Tract Aspergillus Colonization from a Tertiary University Hospital in Thailand.

Positive culture for Aspergillus spp. from respiratory specimens needs to be interpreted together with relevant clinical conditions/settings to differentiate invasive infection from colonization. In this study, we aimed to investigate the association between positive culture for Aspergillus spp. from respiratory specimens and the presence of invasive pulmonary aspergillosis. Hospitalized patients with positive culture for Aspergillus spp. from any respiratory sample were retrospectively recruited. Patients were classified into two groups: those with invasive pulmonary aspergillosis and those with non-invasive aspergillosis/colonization. Two hundred and forty-one patients (48.1% male; mean age: 59.8 ± 14.5 years) were included. The most common Aspergillus spp. was A. fumigatus (21.0%). The most common underlying condition was chronic lung disease (23.7%), followed by solid tumor (22.4%). Myeloproliferative disease (aOR: 69.2, 95% CI: 2.4–1991.9), neutropenia ≥ 10 days (aOR: 31.8; 95% CI: 1.10–920.53), and corticosteroid treatment (aOR: 42.8, 95% CI: 6.5–281.3) were independent predictors of the invasive form. Chronic lung disease was independently inversely related to invasive form (OR: 0.04; 95% CI: 0.003–0.49). Serum galactomannan was positive in 69.2% of patients with invasive aspergillosis (OR: 25.9, 95% CI: 5.2–127.8). All inappropriately treated patients with invasive form died. In conclusion, positive culture for Aspergillus spp. from respiratory specimens with coexisting myeloproliferative disease, neutropenia ≥ 10 days, corticosteroid treatment, or positive serum galactomannan is highly suggestive of invasive pulmonary aspergillosis.

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality. MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression. ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality. DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.

Critically ill patients with COVID-19 show lung fungal dysbiosis with reduced microbial diversity in patients colonized with Candida spp.

BackgroundThe COVID-19 pandemic has intensified interest in how the infection affects the lung microbiome of critically ill patients and how it contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of critically ill patients with COVID-19 in comparison to patients without COVID-19.MethodsWe performed an internal transcribed spacer 2 (ITS2) profiling with the Illumina MiSeq platform on 26 respiratory specimens from patients with COVID-19 as well as from 26 patients with non–COVID-19 pneumonia.ResultsPatients with COVID-19 were more likely to be colonized with Candida spp. ARDS was associated with lung dysbiosis characterized by a shift to Candida species colonization and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in colonized patients with COVID-19. In patients with COVID-19 not colonized with Candida spp., ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and 1 Aspergillus spp.–positive specimen. In addition, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp. among patients with COVID-19.ConclusionOur study underpins that ARDS in patients with COVID-19 is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.

Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016-2019.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016–2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

Invasive aspergillosis in coronavirus disease 2019: a practical approach for clinicians.

Purpose of reviewInvasive pulmonary aspergillosis (IPA) can affect patients with severe coronavirus disease 2019 (COVID-19), but many questions remain open about its very variable incidence across the world, the actual link between the viral infection and the fungal superinfection, the significance of Aspergillus recovery in a respiratory sample, and the management of such cases. This review addresses these questions and aims at providing some clues for the practical diagnostic and therapeutic approaches of COVID-19-associated pulmonary aspergillosis (CAPA) in a clinical perspective.Recent findingsDefinitions have been proposed for possible/probable/proven CAPA, but distinction between colonization and invasive fungal infection is difficult and not possible in most cases in the absence of histopathological proof or positive galactomannan in serum. Most importantly, the recovery of an Aspergillus by a direct (culture, PCR) or indirect (galactomannan) test in a respiratory sample is an indicator of worse outcome, which justifies a screening for early detection and initiation of preemptive antifungal therapy in such cases.SummaryThe COVID-19 pandemic has increased our awareness of IPA among ICU patients. Although current recommendations are mainly based on experts’ opinions, prospective studies are needed to get more evidence-based support for the diagnostic approach and management of CAPA.

Microbiological monitoring of COVID-19 patients in the ICU: a prospective observational study

Objective. To study spectrum of pathogens and the time to colonization of respiratory samples in patients with severe and critical COVID-19 as well as to analyze incidence of nosocomial infections and structure of prescribed antibacterial drugs. Materials and Methods. The prospective observational study included patients aged 18 years and older with confirmed severe and critical COVID-19 from December 2021 to February 2022. During the first 48 hours and then every 2–3 days of hospitalization, a respiratory sample was collected: sputum, tracheal aspirate (if intubated), bronchoalveolar lavage (if bronchoscopy was performed) for microscopy and microbiological examination. Some patients were screened for invasive aspergillosis. Clinical and demographic data, comorbidities, pathogenetic therapy for COVID-19, antibiotic therapy, cases of probable/documented bacterial nosocomial infections, antibiotic-associated diarrhea, and hospital treatment outcomes were recorded. Results. A total of 82 patients were included in this study. Patients with lung parenchyma involvement of more than 50% by computer tomography predominated; most of them (77%) required intubation and mechanical ventilation due to progression of respiratory failure, and 76% of patients had a lethal outcome. During the first 48 hours, a respiratory sample was obtained from 47 patients; the rest of the patients presented with non-productive cough. No growth of microorganisms was detected in 31 (36.8%) cases; clinically significant pathogens were detected in 16 (19.5%) patients. A subsequent analysis included data from 63 patients with a sufficient number of samples for dynamic observation were used. During the first 3 days of ICU stay, the most common bacterial pathogens were Klebsiella pneumoniae without acquired antibiotic resistance and methicillin-susceptible Staphylococcus aureus. From 3rd day and afterwards, an increase in the proportion of Acinetobacter baumannii, other non-fermenting bacteria, and carbapenemresistant Enterobacterales was noted. Among the pathogens causing lower respiratory tract infections, A. baumannii and carbapenem-resistant K. pneumoniae were predominant pathogens and accounted for 76% of cases. Positive galactomannan test results were obtained in 4 cases. Conclusions. The study confirmed importance of bacterial nosocomial infections in patients with severe and critical COVID-19. In the case of the development of nosocomial lower respiratory tract infections, empirical antimicrobial therapy should take into account the predominance of carbapenem-resistant Enterobacteria and A. baumannii, as well as the possibility of invasive aspergillosis.