Proven Invasive Pulmonary Aspergillosis Research Articles

257. Aspergillus Galactomannan Lateral Flow Assay for Rapid Diagnosis of Invasive Aspergillosis in Bronchoalveolar Lavage

BackgroundEarly diagnosis and treatment of invasive pulmonary aspergillosis (IPA) remain the most important factor to reduce mortality. Diagnosis remains a challenge, however, due to unspecific clinical presentation and radiological findings. Only very recently rapid tests for IPA have been developed. The objective of this study was to evaluate the performance of the new CE-marked Aspergillus Galactomannan Lateral Flow Assay (LFA; IMMY, Oklahoma, USA; figure) for IPA in patients with and without hematological malignancies.MethodsThe Aspergillus Galactomannan LFA was retrospectively performed according to the manufacturer’s instructions in 106 previously frozen bronchoalveolar lavage fluid (BAL) samples from 106 patients at risk for IPA (23% with underlying hematological malignancies). Samples were collected between September 2016 and September 2018 at the University of California, San Diego. Performance of the LFA was compared with Galactomannan, BAL culture and the Aspergillus-specific LFD (another rapid test for IPA). IPA was classified according to revised EORTC/MSG criteria.ResultsOverall, 22 patients met criteria of probable or proven IPA, 9 possible IPA, while 75 patients did not fulfill criteria of IPA. Sensitivity of the Apergilllus Galactomanann LFA for probable/proven IPA was 77% (17/22). Sensitivity was similar to BAL GM (77% with a cutoff of 1.0 ODI), but higher compared with the Aspergillus-specific LFD (59%), and BAL culture (23%). The LFA resulted negative in 7/9 cases with possible IPA and 47/73 cases without IPA (overall specificity 66%, 54/82). The less than perfect specificity was driven particularly by non-neutropenic patients (specificity 62%, 43/69), while specificity was 85% among patients with underlying hematological malignancies. Lower specificity among non-neutropenic patients was also observed for the BAL GM (overall 77%, non-neutropenic patients 72%), the Aspergillus-specific LFD (overall 70%, non-neutropenic patients 67%) and BAL culture (overall 90%, non-neutropenic 88%).ConclusionOur study indicates that the LFA may be useful for rapid diagnosis of IPA in BALF when IPA is clinically suspected. The lower specificity in non-neutropenic patients may be explained by limited applicability of the EORTC/MSG criteria in those patients. Disclosures All authors: No reported disclosures.

272. Invasive Pulmonary Aspergillosis: Comparative Analysis in cancer patients with Underlying Hematologic Malignancy vs. Solid Tumor

BackgroundOver the years, the profile of patients with invasive pulmonary aspergillosis (IPA) has extended beyond the commonly associated population with hematologic malignancy (HM) and is now comprising patients with solid tumors and patients with lung diseases. We therefore aimed to compare the clinical characteristics, diagnostic approach and therapeutic outcome of IPA in cancer patients with hematologic malignancies vs. solid tumor (ST).MethodsWe conducted a retrospective study evaluating consecutive cases of proven and probable IPA from March 2004 to December 2016 in a tertiary cancer center. We included patients >18 years with an underlying ST, HM, or Hematopoietic Cell Transplantation (HCT) within 1 year of IPA diagnosis.ResultsA total of 311 patients were analyzed: 225 had HM including HCT and 86 ST. Patients with ST were more likely to have had COPD (33% vs. 8%, P > 0.01) or other underlying pulmonary diseases when compared with HM patients (76% vs. 43%, P < 0.01). Radiation therapy prior to the infection was also notably higher in the ST group than the HM group (48% vs. 14%, P < 0.01). Patients with HM were more likely to have received steroid (38% vs. 15%, P = 0.0001) and have concurrent neutropenia 37% vs. 2%, P < 0.0001). A. fumigatus was most commonly recovered in patients with ST than in patients with HM (66% vs. 38%, P < 0.01). Monotherapy and voriconazole-based primary antifungal therapy were more often prescribed in patients with ST than in patients with HM (87% vs. 56%, P < 0.0001 and 77% vs. 53%, P = 0.0002 respectively). Complete or partial successful response to therapy was recorded in 66% of patients with ST compared with 40% in the HM group (P = 0.0001). IPA attributable mortality within 12 weeks was significantly higher in the HM than in the ST group (30% vs. 18%, P = 0.04).ConclusionMonotherapy with voriconazole were more often prescribed in patients with ST than in patients with HM. Patients with ST had a better response to antifungal therapy and a lower IPA attributable mortality within 12 weeks compared with those with HM.Disclosures All authors: No reported disclosures.

Clinical application of Aspergillus lateral flow device in bronchoalveolar lavage fluid of patients with classic risk factors for invasive pulmonary aspergillosis.

The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. We evaluated the performance characteristics of a newly formatted Aspergillus lateral flow test, AspLFD, in bronchoalveolar lavage (BAL) fluid from patients with classic risk factors for IPA. Prospectively banked BAL samples from 14 patients with proven or probable IPA defined by EORTC/MSG criteria and 28 BAL samples from age-matched high-risk patients without IPA were tested with AspLFD according to manufacturer's directions. Results were read by two independent observers, and test performance was calculated. Age, gender and underlying risk factors, except for neutropenia and haematological malignancy, were similar between IPA cases and controls. Seven patients (50%) in the IPA group received a mould-active agent within 5days prior to bronchoscopy compared with only three patients (11%) in the control group, P=.004. Of 14 patients with proven/probable IPA, AspLFD was positive in 3 and negative in 9; two tests yielded invalid results. All 28 control patients had a negative AspLFD test. AspLFD showed low sensitivity (25%, 95% CI: 5.5% to 57.2%), but high specificity (100%. (95% CI: 87.7% to 100%). A positive AspLFD test in BAL fluid of patients with classic risk factors for IPA could be useful to support the diagnosis of proven/probable IPA because of its high specificity. However, as a stand-alone test for IPA, the use of AspLFD is limited by low sensitivity.

Invasive pulmonary aspergillosis in critically ill patients with hematological malignancies.

Invasive pulmonary aspergillosis (IPA) is a dreadful event in patients with hematological malignancies (HM). Recent advances have standardized diagnostic, prophylactic and curative therapeutic strategies. We sought to assess whether these advances actually translate into improved survival in critically ill patients with acute respiratory failure and IPA. This was a retrospective, multicenter study. Adult patients with HM, IPA, admitted to the ICU for acute respiratory failure over a 20-year period (January 1998-December 2017) were included. A cox regression model was used to identify variables independently associated with day-90 survival. Overall, 219 patients were included [138 (63%) men, median age 55 (IQR 44-64)]. Acute myeloid leukemia (30.1%) and non-Hodgkin lymphoma (22.8%) were the most frequent malignancies, and 53 (24.2%) were allogeneic stem cell recipients. Day-1 SOFA score was 9 [7-12]. Most patients presented with probable IPA, whereas 15 (7%) underwent lung biopsies or pleurocentesis and met criteria for proven IPA. Overall ICU and day-90 mortality were, respectively, 58.4% and 75.2% (80.4% if invasive mechanical ventilation) without any significant improvement over time. By multivariable analysis adjusted on day-1 SOFA score and ventilation strategies, voriconazole use (HR 0.49, CI 95 0.34-0.73, p < 0.001) and an ICU admission after 2010 (HR 0.67, 0.45-0.99, p = 0.042) were associated with increased survival, whereas a diffuse radiologic pattern (HR 2.07, CI 95 1.33-3.24, p = 0.001) and delayed admission to the ICU (HR 1.51, CI 95 1.05-2.16, p = 0.026) were independently associated with increased mortality. IPA is associated with high mortality rates in critically ill patients with acute respiratory failure. Routine voriconazole and prompt ICU admission are warranted.

Invasive pulmonary aspergillosis: comparative analysis in cancer patients with underlying haematologic malignancies versus solid tumours

Invasive pulmonary aspergillosis (IPA) is commonly associated with haematologic malignancies but also occurs with solid tumours. To compare the diagnostic approaches and therapeutic outcomes for IPA between patients with haematologic malignancies and solid cancers. A retrospective study was conducted evaluating consecutive cases of proven and probable IPA from 2004 to 2016. Patients >18 years of age with an underlying solid tumour, haematologic malignancy, or haematopoietic cell transplantation (HCT) within one year of IPA diagnosis were included. Of the 311 patients analysed, 225 had haematologic malignancies and 86 had solid tumours. Patients with solid tumours were more likely to have had chronic obstructive pulmonary disease (COPD) or other pulmonary diseases, have Aspergillus fumigatus infections, and have received radiotherapy before IPA occurrence than were those with haematologic malignancies (all P<0.01). Antifungal monotherapy and voriconazole-based therapy were more often prescribed in the solid group (87% vs 56%, P<0.0001, and 77% vs 53%, P=0.0002, respectively). The median duration of primary antifungal therapy was longer in the solid group (64 days vs 20 days, P<0.0001). Complete or partial response to antifungal therapy was recorded in 66% of the solid group and 40% of the haematologic group (P=0.0001). At 12 weeks, overall mortality was similar in both groups, but IPA-attributable mortality was higher in the haematologic group (30% vs 18%, P=0.04). Monotherapy was more often prescribed in patients with solid tumours than in patients with haematologic malignancies. Patients with solid tumours had better antifungal therapy response and lower 12-week IPA-attributable mortality than did those with haematologic malignancies.

Distribution of Galactomannan antigen in BAL and serum samples among Aspergillus isolates and its correlation with culture among Immunocompetent and Immunocomporomised patients in Aligarh region, a north India town

Background: Aspergillosis is one of the most common fungal infection among both general patients and immunocompromised individuals. Methods: The study was carried out on 2 groups of patients: immunocompetent and immunocompromised comprising of a total of 90 patients. Microscopy, culture, identification of isolates was done and some specialised tests on serum and BAL for antigen detection were performed. Result: Most of the patients i.e., 47 (31.3%) were between 31-40 years with a mean age of 32.5 years. The male to female ratio was 1.8:1. Galactomannan antigen was positive in 13 (28.9%) BAL samples and in 15 (33.3%) serum samples wherein the 45 BAL samples represented immunocompetent cases and 45 serum samples represented immunocompromised cases. Sensitivity and specificity of GM assay in BAL samples were found to be 100% and 97% respectively. On the other hand, sensitivity and specificity in serum samples were found to be 94.1% and 100% respectively. All patients were categorized into 4 categories as proven IPA, probable IPA, possible IPA and non-IPA. 22 (24.4%) patients were of proven invasive pulmonary aspergillosis (IPA), 7 (7.8%) of probable IPA, 2 (2.2%) belonged to possible IPA while 59 (65.5%) were of non IPA. All of the cases of proven IPA were positive on culture. Conclusion: GM assay in BAL is a very sensitive and specific marker for Aspergillosis while in case of serum samples it is somewhat lesser sensitive.

Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience.

Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3months was the primary end-point. Clinical response and mortality at 12months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point. Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12months (HR 0.258; 95% CI 0.072-0.922; p = 0.037). Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.

Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients Treated with a Preemptive/ Targeted Antifungal Therapy Strategy: 4 Year Follow Up

Purpose Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). Centers employing universal antifungal prophylaxis have reported up to 60% of the IPA episodes occur after the first year post transplant. We previously reported the incidence of IPA during the first year after transplant in a cohort of LTRs treated with preemptive prophylaxis. It is unclear how a preemptive/targeted antifungal therapy strategy impacts the incidence of IPA beyond 1 year post transplant. Methods Retrospective study of consecutive LTRs from 1 Jan 2010 to 31 Dec 2014 with a 4 year follow up on those who survived at least 1 year. Incidence of probable/ proven IPA, bronchoalveolar (BAL) Aspergillus spp. cultures or Galactomannan (GM) positivity (index value >1) were recorded during this period. IPA, Aspergillus colonization and preemptive/ targeted prophylaxis were defined according to criteria established by ISHLT. Patients with probable/ proven IPA, positive Aspergillus cultures and/ or GM received preemptive/ targeted therapy. Results There were a total of 350 consecutive LTRs with 1078 bronchoscopies . 82% (288/350) were double lung transplants, with median age of 53.9 yrs. 73% (254/350) LTRs did not receive induction immunosuppression with basiliximab or thymoglobulin . 15% (52/350) LTRs had positive BAL for GM and/ or Aspergillus cultures beyond 1 year of transplantation. Median time to positive Aspergillus culture or positive GM was 608 days. Figure 1 shows the distribution of positive Aspergillus culture and GM in the cohort after 1 year . 3% (10/350) LTRs met criteria for probable IPA. Beyond 1 year, none of the Aspergillus culture or GM negative patients had biopsy proven IPA. All cause mortality in LTRs with IPA was 10% (1/10). Conclusion Undergoing a preemptive strategy beyond 1 year post transplantation resulted in a low frequency of treatment for IPA when assessing positive BAL cultures or GM.

359. Baseline Serum Aspergillus Galactomannan Index Among Aspergillus Species in Hematologic Malignancies Patients With Invasive Pulmonary Aspergillosis

BackgroundMost of the information regarding serum Aspergillus galactomannan (sAGM) index in patients with invasive pulmonary aspergillosis (IPA) and hematological malignancies (HM) is derived by infections caused by Aspergillus fumigatus, the predominant Aspergillus species causing IPA. It is unclear if differences exist in sAGM in IPA caused by non-fumigatus Aspergillus species.MethodsWe analyzed all consecutive patients with proven or probable culture-documented IPA (EORTC/MSG criteria) at MD Anderson Cancer Center (2006–2017) who had an sAGM obtain within a week of IPA diagnosis (day −6 to day 0 of fungal culture). The sAGM result was categorized as either undetectable (GM = 0), negative (0.0 > GM < 0.5) or ≥ than a 0.5 index value. Baseline demographic characteristics and 42-day crude mortality after the diagnosis of IPA were collected.ResultsWe identified 72 (proven in 4, probable in 68) patients with culture-documented IPA. Most common HM was AML in 34 (47.2%) patients and CLL in 15 (20.8%) patients. Most (47/72, 65, 2%) patients developed IPA despite mold-active antifungals. Forty-three (60%) patients had A. fumigatus, 19 (26%) A. terreus, and 10 (14%) A. flavus. Mortality at 42 day was 22.2% (16/72) patients. Serum AGM at the baseline was undetectable in only one (2%) Aspergillus fumigatus IPA. Serum AGM positivity was seen in 28 (65%), 10 (53%), and five (50%), among the Aspergillus fumigatus, terreus, and flavus species, respectively (P = 0.52), with a median sAGM level of 1.32 (0.50–9.36), 0.87 (0.50–9.70), and 1.11 (0.57–8.58), respectively, P = 0.99. There were not significant differences in baseline neutropenia, extent of lung involvement by chest CT, prior mold-active antifungal use, prior SCT as well as 42-day mortality among patients with IPA caused by each of the three Aspergillus species.ConclusionIn the setting of common prior mold-active antifungal use, we found no apparent differences in sAGM among Aspergillus species causing IPA in HM patients. Mortality was comparable and worse in patients with high baseline sAGM levels.Disclosures D. P. Kontoyiannis, Merck: Consultant, Research support and Speaker honorarium. Pfizer: Consultant, Research support. Astellas: Consultant, Research support and Speaker honorarium. Gilead: Speaker’s Bureau, Speaker honorarium. F2G Inc.: Speaker’s Bureau, Speaker honorarium. Cidara Inc.: Speaker’s Bureau, Speaker honorarium. Jazz Pharmaceuticals: Speaker’s Bureau, Speaker honorarium.

356. Bronchoalveolar Lavage Fluid Cytology by GMS Stain for the Diagnosis of Invasive Pulmonary Aspergillosis in Patients With Hematologic Malignancies: Analysis of 67 Episodes

BackgroundThe yield of direct fungal visualization by GMS (Gomori–methenamine–silver) stain in bronchoalveolar lavage (BAL) cytology has rarely been studied in the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies (HM).MethodsWe analysed a series of patients with proven or probable culture-documented IPA (EORTC/MSG criteria) in HM patients (1999–2015). All patients had BAL cultures that were positive for Aspergillus spp. and had concurrently obtained BAL cytology GMS available for analysis.ResultsWe identified 67 such patients. BAL cytology based on GMS showed hyalohyphomycetes consistent with Aspergillus in 28/67 (41.8%) patients, whereas only in 2/67 (3.6%) direct smear Calcofluor White stain was positive. Based on BAL GMS cytology, co-infections were identified in six patients: two Pneumocystis and five viral infections with cytopathic changes (one had both). The yield of cytology was not different in patients with IPA caused by non-fumigatus Aspergillus, although patients with IPA and >1 Aspergillus in BAL culture had more often positive cytology GMS (100% vs. 0%, p 0.027). Cytology was also more often positive when obtained from a lesion-targeted BAL as compared with non-targeted bronchial washings (60.7% vs. 7.1%, p 0.038). Patients with IPA and cavitary lesions (32.1% vs. 5.1%, P = 0.006), history of SCT (64.3% vs. 33%, P = 0.015) or prior exposure to itraconazole (75% vs. 41%, P = 0.007) had positive cytology GMS results more often than did patients without these characteristics. In the multivariate analysis, only cavitary lesions were significantly associated with positive BAL GMS cytology.ConclusionGMS stain in cytology of BAL in patients with HM and culture-documented IPA had a sensitivity of 41.8% and was more often positive in patients with cavitary lesions. Although there were no differences in the proportion of GMS-positive cytology rates among differing Aspergillus spp. causing IPA, mixed Aspergillus spp. IPA was associated with an increase in positive cytology. BAL cytology was diagnostic for co-infections in more than 10% of patients. BAL cytology should be part of the diagnostic wok up in HM patients with suspected IPA.Disclosures All authors: No reported disclosures.

Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies.

INTRODUCTION:Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking.METHODS:We performed a prospective case–control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Cases were subjects with hematological diagnoses who met established revised definitions for proven or probable IPA established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG, 2008), without the use of BAL GM results. Exclusion criteria included the use of piperacillin/tazobactam and use of antifungals that were active against Aspergillus spp. before bronchoscopy. There were two control groups: patients with hematological diagnoses not meeting definitions for proven or probable IPA and patients with nonhematological diagnoses with no evidence of aspergillosis. Following bronchoscopy and BAL, GM testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.RESULTS:There were 51 cases and 20 controls. Cases had higher BAL fluid GM OD indices (ODIs) (mean: 1.27 and range: 0.4–3.78) compared with controls (mean: 0.26 and range: 0.09–0.35). Receiver operating characteristic analysis demonstrated an optimum ODI cutoff of 1.0, with high specificity (100%) and sensitivity (87.5%) for diagnosing IPA.CONCLUSIONS:Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.

Is Bulpa criteria suitable for the diagnosis of probable invasive pulmonary Aspergillosis in critically ill patients with chronic obstructive pulmonary disease? A comparative study with EORTC/ MSG and ICU criteria

BackgroundThree diagnostic criteria have been proposed used for invasive pulmonary aspergillosis (IPA) diagnosis, namely EORTC/ MSG criteria, Bulpa criteria and intensive care unit (ICU) criteria. The Bulpa criteria were proposed to diagnose IPA in chronic obstructive pulmonary disease (COPD) patients specially. Our aim is to verify that whether the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients compared with the other two criteria.MethodsWe included critically ill COPD patients admitted to the ICU from April 2006 to August 2013. Patients were classified into four populations: population one (n1 = 59) comprised all included patients; population two (n2 = 24) comprised patients with positive mycological findings (both positive cultures and positive serologic tests); population three (n3 = 18) comprised patients with positive lower respiratory tracts (LRTs) isolation; and population four (n4 = 5) comprised proven IPA patients with histopathology. Patients in four groups were diagnosed as probable IPA using three criteria respectively, and the “diagnostic rate” of each criteria were compared with each other. Then, the reasons for differences in “diagnostic rate” were analyzed in population two. Finally, the modified Bulpa criteria were proposed.ResultsBulpa criteria yielded the highest “diagnostic rate” of probable IPA followed by the ICU criteria, while the EORTC/ MSG criteria provided the lowest rates in four populations (the “diagnostic rate” of probable IPA was 33.9%, 16.9% and 6.8% in population one, p = 0.001; 83.3%, 41.7% and 16.7% in population two, p < 0.001; 100%, 55.6% and 22.2% in population three, p < 0.001; 100%, 60% and 20% in population four, p = 0.036). The reasons for the highest “diagnostic rate” by Bulpa criteria were its less strict requirements regarding the doses/courses of steroid use and typical computed tomography (CT) findings. Finally, the modified Bulpa criteria for probable IPA were proposed for critically ill COPD patients admitted to ICU, mainly involving revised interpretations of microbiological findings.ConclusionsAmong the existing three criteria, the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients admitted to ICU. A modified criteria maybe proposed for better diagnosis,and its clinical validity need to be verified in future studies.

Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients.

Background We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results Ten cases of IPA were diagnosed. ROC data demonstrated that, for diagnosing IPA, an optimal cutoff value for GM in BALF of 0.76 yielded a sensitivity of 100.0% and a specificity of 76.2%. Symptoms and radiological findings had no significant difference between proven or probable IPA group and non-IPA group. In our case-control analysis, although nine patients with false-positive results received treatment with Piperacillin/tazobactam, there was no significant difference between case and control group. Conclusions BALF GM detection is a valuable adjunctive diagnostic tool. Our retrospective study suggests that the optimal value of GM detection in BALF is 0.76 in nonneutropenic patients.

Aspergillus-positive lower respiratory tract samples in patients with the acute respiratory distress syndrome: a 10-year retrospective study.

BackgroundThe detection of Aspergillus spp. in endotracheal aspirate cultures of mechanically ventilated patients may reflect either colonization or infection. However, little is known about the prevalence and the impact on outcome of respiratory tract sample positive for Aspergillus during the acute respiratory distress syndrome (ARDS).MethodsWe conducted a monocentric, retrospective study over a 10-year period (January 2006–December 2015) in the ICU of a university hospital. All consecutive adult patients with ARDS were included, and the diagnosis of invasive pulmonary aspergillosis was assessed using a previously validated algorithm.ResultsIn total, 423 ARDS patients were included with 35 patients [8.3 %, 95 % CI (5.4–10.6)] having at least one respiratory tract sample positive for Aspergillus (Aspergillus+ patients) after a median delay of 3 days (1–11) following ICU admission. Comorbidities did not differ between Aspergillus+ and Aspergillus− patients except for more frequent immunosuppression in Aspergillus+ patients (40 vs. 22 %; p = 0.02). There was no difference between Aspergillus− and Aspergillus+ patients regarding in-ICU mortality, ventilator-free days at day 28, and incidence of ventilator-associated pneumonia, but need for renal replacement therapy was higher in Aspergillus+ patients than in others (49 vs. 27 %; p = 0.01). Seventeen [4.0 %, 95 % CI (2.1–5.9)] patients had putative/proven aspergillosis. After adjusting on covariates associated with ICU mortality, putative/proven aspergillosis was associated with in-ICU mortality [aOR = 9.58 (1.97–46.52); p = 0.005], while Aspergillus colonization was not [aOR = 0.64 (0.21–1.99); p = 0.44].ConclusionsEight percent of ARDS patients had Aspergillus spp.-positive respiratory tract cultures. These had a higher risk of mortality only when categorized as having putative or proven invasive pulmonary aspergillosis.

Clinical analysis of 16 cases of invasive pulmonary aspergillosis in children

To investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children. The clinical data of 16 cases of proven or probable IPA who had been in our Hospital from January 2006 to June 2014 were retrospectively analyzed. Among the 16 patients, 11 were males and 5 were females. One child had proven IPA and 15 children had probable IPA. Host risk included long duration use of multiple broad-spectrum antibiotics in 16 cases, neutropenia in 9 cases, invasive mechanical ventilation in 3 cases, primary immunodeficiency disease in 2 cases, long-term use of glucocorticoids in 2 cases, measles in 2 cases, and congenital pulmonary hypoplasia in 1 case. Fever, cough and expectoration were present in all the children with IPA. At the time of diagnosis, the halo sign and subpleural wedge consolidation shadows were more common in neutropenia group (5/9, 7/9) than those in non-neutropenia group(0/7, 1/7)(P<0.05). The cavities and"air-crescent sign"were more common after 15 days to 1 month when the children had been treated with anti-aspergillosis drugs than that at the onset of diagnosis of IPA (P<0.05). The positive rate of serum galactomannan (GM) test was higher than that of sputum culture and serum G test (P<0.05). Thirteen children received voriconazole, in 7 of the children the treatment was effective. Neutropenia were the common host risk factors in children with IPA. Subpleural wedge consolidation shadows, the halo sign and the"air-crescent"sign were highly suggestive of the diagnosis of IPA in children. Subpleural wedge consolidation shadows and the halo sign were more common in neutropenia group than in non-neutropenia group in the early stage of the course. Serum GM test played an important role in the diagnosis of IPA in children. Voriconazole was effective in majority of the children with IPA.

Influence of mould-active antifungal treatment on the performance of the Aspergillus-specific bronchoalveolar lavage fluid lateral-flow device test

The effect of mould-active antifungal (AF) therapy/prophylaxis on the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) was evaluated. This was a retrospective analysis of patients diagnosed with probable or proven IPA (according to revised EORTC/MSG criteria) at the Medical University of Graz (Austria) and the University Hospital of Mannheim (Germany) between February 2011 and December 2014. In total, 60 patients with 63 bronchoalveolar lavage fluid (BALF) samples were included in the analysis. Patient charts were reviewed regarding AF treatment at the time of bronchoscopy, and the influence of AFs on the performance of the LFD and BALF galactomannan (GM) ELISA results was calculated. Overall, 54 patients (57 BALF samples) had probable IPA and 6 patients (6 samples) had proven IPA. In 21/63 samples (33%) (from 19 patients), systemic mould-active AFs had been initiated before bronchoscopy. Of 63 BALF samples, 16 (25%) yielded a false-negative LFD result. The sensitivity of the LFD for probable/proven IPA was significantly lower in those receiving mould-active AFs compared with those without (52% vs. 86%; P=0.006). Similar results were found for BALF GM, with sensitivities decreasing under systemic AFs (71% vs. 95%, P=0.013 with the 0.5 ODI cut-off; 52% vs. 81%, P=0.036 with the 1.0 cut-off). These results suggest that the sensitivity of the BALF LFD and BALF GM assays may be reduced in the presence of mould-active AF treatment. Negative results in patients on AFs should therefore be interpreted with caution.

Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis

Because there are no available molecular markers for pulmonary mucormycosis (PM), which has low culture sensitivity, early diagnosis and treatment rely heavily on imaging modes such as computed tomography (CT). However, there are limited data comparing CT findings for PM with those for invasive pulmonary aspergillosis (IPA). Adult patients who met the modified criteria for proven and probable PM (over an 11-year period) and IPA (over a 6-year period, owing to the availability of the galactomannan assay) according to the modified European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions were retrospectively enrolled. IPA cases were selected at a 1 : 4 (PM/IPA) ratio. Thoracic CT scans were reviewed by two experienced radiologists blinded to the patients' demographics and clinical outcomes. A total of 24 patients with PM, including 20 (83%) with proven PM and four (17%) with probable PM, and 96 patients with IPA, including 12 (13%) with proven IPA and 84 (87%) with probable IPA, were eventually analysed. The reverse halo sign was more common in patients with PM (54%) than in those with IPA (6%, p < 0.001), whereas some airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, were more common in patients with IPA (IPA 52% vs. PM 29%, p 0.04; IPA 49% vs. PM 21%, p 0.01; IPA 34% vs. PM 4%, p 0.003, respectively). The reverse halo sign was more common, and airway-invasive features were less common, in patients with PM than in those with IPA. These findings may help physicians to initiate Zygomycetes-active antifungal treatment earlier.

Invasive aspergillosis in neutropenic patients during hospital renovation: effectiveness of mechanical preventive measures in a prospective cohort of 438 patients.

Aspergillus species are the main cause of invasive fungal disease for patients with severe and prolonged neutropenia. Building or renovation works have been shown as one of the major causes of outbreaks of aspergillosis. This study aimed to assess the effectiveness of introduction and adaptation by air sampling of mechanical preventive measures on the incidence of invasive pulmonary aspergillosis in neutropenic patients during hospital renovation. All of the patients admitted for prolonged and severe neutropenia during a renovation period from 2003 to 2008 were prospectively enrolled. Invasive pulmonary aspergillosis (IPA) cases were classified as possible, probable, and proven, according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group criteria. The effectiveness of preventive measures was determined by air sampling. We recorded 705 hospitalizations for neutropenia concerning 438 patients. The majority of hospitalized neutropenic patients was treated for acute leukemia (38.3 %), followed by patients suffering from non-Hodgkin and Hodgkin lymphomas (33 %). The total cumulative incidence of probable and proven IPA was 4.1 %. Risk factors for developing IPA were underlying disease, treatment course at the time of hospitalization, and the mean duration of hospitalization and of neutropenia. In this prospective study, the incidence of invasive pulmonary aspergillosis did not increase in neutropenic patients during a renovation period because of efficient mechanical preventive measures systematically adjusted using the results of air sampling.

Immune reconstitution inflammatory syndrome in neutropenic patients with invasive pulmonary aspergillosis

Clinical and radiologic deterioration is sometimes observed during neutrophil recovery in patients with invasive pulmonary aspergillosis (IPA). This deterioration can be caused by immune reconstitution inflammatory syndrome (IRIS) as well as by progression of the IPA. However, there is limited data on IRIS in neutropenic patients. Over a 6-year period, adult patients with neutropenia who met the criteria for probable or proven IPA by the revised EORTC/MSG definition were retrospectively enrolled. IRIS was defined as de novo appearance or worsening of radiologic pulmonary findings temporally related to neutrophil recovery, with evidence of a decrease of 50% in serum galactomannan level. Of 153 patients, 36 (24%, 95% CI 18%-31%) developed IRIS during neutrophil recovery. More of these patients received voriconazole than did those with non-IRIS (42% vs. 25%, P = 0.05). Thirty- and ninety-day mortalities were lower in the patients with IRIS than in those with non-IRIS (11% vs. 33%, P = 0.01, and 33% vs. 58%, P = 0.01, respectively). IRIS is relatively common among neutropenic patients with IPA, occurring in about one quarter of such patients. It is associated with voriconazole use and has a good prognosis.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.