galactomannan and Critical-Illness

Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing conditions, e.g. corticosteroid treatment, chronic obstructive pulmonary disease, liver cirrhosis, solid organ cancer, HIV infection and transplantation. Diagnosis is challenging because the signs and symptoms are non-specific, and initiation of additional diagnostic examinations is often delayed because clinical suspicion is low. Isolation of an Aspergillus species from the respiratory tract in critically ill patients, and tests such as serum galactomannan, bronchoalveolar lavage 1-3-β-d-glucan and specific PCR should be interpreted with caution. ICU patients should start adequate antifungal therapy upon suspicion of invasive aspergillosis, without awaiting definitive proof. Voriconazole, and now isavuconazole, are the drugs of choice. Mucormycosis is a rare, but increasingly prevalent disease that occurs mainly in patients with uncontrolled diabetes mellitus, immunocompromised individuals or previously healthy patients with open wounds contaminated with Mucorales. A high proportion of cases are diagnosed in the ICU. Rapidly progressing necrotizing lesions in the rhino-sinusal area, the lungs or skin and soft tissues are the characteristic presentation. Confirmation of diagnosis is based on demonstration of tissue invasion by non-septate hyphae, and by new promising molecular techniques. Control of underlying predisposing conditions, rapid surgical resection and administration of liposomal amphotericin B are the main therapeutic actions, but new agents such as isavuconazole are a promising alternative. Patients with mucormycosis receive a substantial part of their care in ICUs and, despite advances in diagnosis and treatment, mortality remains very high.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Critical Illness; Galactose; Humans; Immunocompromised Host; Intensive Care Units; Invasive Fungal Infections; Lung Diseases, Fungal; Mannans; Mucor; Mucormycosis; Nitriles; Opportunistic Infections; Pyridines; Respiratory System; Triazoles; Voriconazole

During recent years, a rising incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic critically ill patients has been reported. Critically ill patients are prone to develop disturbances in immunoregulation during their stay in the ICU, which render them more vulnerable for fungal infections. Risk factors such as chronic obstructive pulmonary disease (COPD), prolonged use of steroids, advanced liver disease, chronic renal replacement therapy, near-drowning and diabetes mellitus have been described. Diagnosis of IPA may be difficult and obtaining histo- or cytopathological demonstration of the fungus in order to meet the gold standard for IPA is not always feasible in these patients. Laboratory markers used as a non-invasive diagnostic tool, such as the galactomannan antigen test (GM), 1,3-beta-glucan, and Aspergillus PCR, show varying results. Antifungal therapy might be considered in patients with persistent pulmonary infection who exhibit risk factors together with positive cultures or sequentially positive GM and Aspergillus PCR in serum, in whom voriconazole is the drug of choice. The benefit of combination antifungal therapy lacks sufficient evidence so far, but this treatment might be considered in patients with breakthrough infections or refractory disease.

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; beta-Glucans; Critical Illness; DNA, Fungal; Drug Therapy, Combination; Galactose; Humans; Intensive Care Units; Lung Diseases, Fungal; Mannans; Opportunistic Infections; Polymerase Chain Reaction; Risk Factors

An algorithm for distinguishing invasive pulmonary aspergillosis (IPA) in critically ill patients (AspICU) has been proposed but not tested.. This was a prospective observational study applying the AspICU protocol to patients with positive Aspergillus culture (PAC group) and those with negative aspergillus culture but positive galactomannan test in respiratory tract samples (only positive galactomannan (OPG group)). Patients underwent a standardized diagnostic workup with bronchoscopy, computed tomography (CT), and galactomannan determination in serum and bronchoalveolar lavage fluid (BALF).. We included 85 patients in the study. Of these, 43 had positive aspergillus cultures and 42 patients had only a positive galactomannan test. There were no statistically significant differences in baseline characteristics, underlying conditions or ICU scores between the two groups. The galactomannan titre in BALF was significantly higher in the positive aspergillus culture (PAC) group (enzyme immunoassay (EIA) 5.9, IQR 3.2-5.7) than in the OPG group (EIA 1.7, IQR 0.9-4.5) (p < 0.001). Classic features of IPA were detected on CT in 37.5 % and 36.6 % of patients in the PAC and OPG groups, respectively. There were no statistically significant differences between the PAC and the OPG group in relation to AspICU or European Organization for the Research and Treatment of Cancer (EORTC) criteria. A positive aspergillus culture was a stronger trigger for initiating antimycotic treatment than positive BALF galactomannan: 88.4 % of patients in the PAC group were regarded by clinicians as having IPA and received antimycotic treatment as opposed to 59.5 % in the OPG group (p = 0.002). The 180-day mortality was 58.1 % in the PAC group and 59.5 % in the OPG group.. The inclusion of BALF galactomannan as an additional entry criterion for the AspICU clinical algorithm could increase the diagnostic sensitivity for IPA in ICU patients.. The study was registered at ClinicalTrials.gov (registration number NCT01866020 ) on 27 May 2013.

Topics: Aged; Aged, 80 and over; Antifungal Agents; Critical Illness; Galactose; Humans; Intensive Care Units; Mannans; Prospective Studies; Pulmonary Aspergillosis; Therapeutic Irrigation

COVID-19-associated pulmonary aspergillosis (CAPA) incidence varies depending on the country. Serum galactomannan quantification is a promising diagnostic tool since samples are easy to obtain with low biosafety issues. A multicenter prospective study was performed to evaluate the CAPA incidence in Argentina and to assess the performance of the lateral flow assay with digital readout (Sōna Aspergillus LFA) as a CAPA diagnostic and screening tool. The correlation between the values obtained with Sōna Aspergillus LFA and Platelia® EIA was evaluated. In total, 578 serum samples were obtained from 185 critically ill COVID patients. CAPA screening was done weekly starting from the first week of ICU stay. Probable CAPA incidence in critically ill patients was 10.27% (19/185 patients when LFA was used as mycological criteria) and 9% (9/100 patients when EIA was used as mycological criteria). We found a very good correlation between the two evaluated galactomannan quantification methods (overall agreement of 92.16% with a Kappa statistic value of 0.721). CAPA diagnosis (>0.5 readouts in LFA) were done during the first week of ICU stay in 94.7% of the probable CAPA patients. The overall mortality was 36.21%. CAPA patients' mortality and length of ICU stay were not statistically different from for COVID (non-CAPA) patients (42.11 vs 33.13% and 29 vs 24 days, respectively). These indicators were lower than in other reports. LFA-IMMY with digital readout is a reliable tool for early diagnosis of CAPA using serum samples in critically ill COVID patients. It has a good agreement with Platelia® EIA.. The incidence of COVID-associated pulmonary aspergillosis (CAPA) in critically-ill Argentinian patients was established (10.27%). Serum galactomannan quantification was useful as a screening tool for this mycosis. A good agreement between Platelia® EIA and Sōna Aspergillus LFA is reported.

Topics: Animals; Argentina; Aspergillus; COVID-19; Critical Illness; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Prospective Studies; Pulmonary Aspergillosis; Sensitivity and Specificity

Coronavirus disease 2019 or COVID-19 is a new infectious disease responsible for potentially severe respiratory impairment associated with initial immunosuppression. Similarly to influenza, several authors have described a higher risk of fungal infection after COVID-19, in particular for invasive pulmonary aspergillosis. The main objective here is to define the prevalence of invasive pulmonary aspergillosis (IPA) in a cohort of COVID-19 patients with moderate to severe acute respiratory disease syndrome (ARDS).. We conducted a large monocentric retrospective study investigating all the ventilated COVID-19 patients with ARDS hospitalized at Valenciennes' general hospital, France, between March 15, 2020 and April 30, 2020. In the center a systematic IPA screening strategy was carried out for all ARDS patients, with weekly tests of serum galactomannan and beta-D-glucan. Bronchoalveolar lavage with culture and chest CT scan were performed when the serum assays were positives.. A total of 54 patients were studied. Their median age was 65 years, and 37 of the patients (71%) were male. Two patients had chronic immunosuppression and among all the patients, only 2 non-immunocompromised presented a putative IPA during their stay.. The prevalence of IPA in this cohort of COVID-19 patients (3.7%) is not higher than what is described in the other ARDS populations in the literature. These results are however different from the previous publications on COVID-19 patients and must therefore be confirmed by larger and multicentric studies.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Comorbidity; COVID-19; Critical Illness; Female; France; Galactose; Hospitals, General; Humans; Immunocompromised Host; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Opportunistic Infections; Respiration, Artificial; Respiratory Distress Syndrome; Retrospective Studies; Risk Factors

Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.. We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.. CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.. CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.

Topics: Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; COVID-19; Critical Illness; Female; Galactose; Humans; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Pneumonia, Viral; Prospective Studies; Respiration, Artificial; SARS-CoV-2; Superinfection

To explore the diagnostic value of a galactomannan (GM) detection for non-immunocompromised critically ill patients with influenza-associated aspergillosis (IAA). In this retrospective case-control study, we explored the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic (ROC) curve (AUC) of serum and bronchoalveolar lavage fluid (BALF) GM tests by four detection strategies at different detection time points and with different compound modes. In total, 90 patients were evaluated. The AUC values of the second serum GM test, the first and second BALF GM tests, were significantly higher (0.839 (95% CI 0.716 to 0.963), P < 0.01; 0.904 (95% CI 0.820 to 0.988), P < 0.01; 0.827 (95% CI 0.694 to 0.961), P = 0.043) than that of the first serum GM test (0.548 (95% CI 0.377 to 0.718)). We found that at least one positive result on two consecutive serum GM tests (0.719 (95% CI 0.588 to 0.849)) was the best compared with the first positive test (0.419 (95% CI 0.342 to 0.641), P < 0.01) and positives on two consecutive tests (0.636 (95% CI 0.483 to 0.790), P = 0.014). However, there were no differences between those three detection strategies of BALF GM. The BALF GM test might have a better diagnostic value for IAA in the ICU than the serum GM test. A possible cutoff value of 1.0 to 1.3 was set for GM from BALF specimens for IAA. A single serum GM test is not routinely recommended, but at least one positive result on two consecutive tests appeared to be useful.

Topics: Adult; Aged; Aspergillosis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Clinical Laboratory Techniques; Critical Illness; Female; Galactose; Humans; Influenza, Human; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Seasons; Sensitivity and Specificity

Topics: Aged; Antibodies, Monoclonal, Humanized; Cohort Studies; Coinfection; COVID-19; Critical Illness; Galactose; Humans; Incidence; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Pandemics; Respiration, Artificial; Switzerland

Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options.. We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings.. Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis.. In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.

Topics: Aged; Aged, 80 and over; Autopsy; Betacoronavirus; Biopsy; Biopsy, Large-Core Needle; Bronchoalveolar Lavage Fluid; Coinfection; Coronavirus Infections; COVID-19; Critical Illness; Female; Galactose; Humans; Lung; Lung Diseases, Interstitial; Male; Mannans; Middle Aged; Pandemics; Phenotype; Pneumonia, Viral; Pulmonary Aspergillosis; Pulmonary Embolism; Respiratory Distress Syndrome; SARS-CoV-2; Tomography, X-Ray Computed

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Aspergillus fumigatus; beta-Glucans; Bronchoalveolar Lavage Fluid; COVID-19; Critical Illness; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Proteoglycans; Real-Time Polymerase Chain Reaction; SARS-CoV-2; United Kingdom

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in the intensive care unit (ICU). The ICU criteria were proposed to diagnose IPA in critically ill patients. This study aims to evaluate the usefulness of ICU criteria for diagnosis and treatment of IPA in nonhematologic patients in the ICU. We retrospectively reviewed 103 ICU patients with positive galactomannan test in blood and respiratory tract from January 1, 2016, to May 31, 2017. We excluded patients with hematologic malignancy. We divided the treatment and non-treatment groups according to the IPA treatment. We compared the baseline characteristics and outcomes between two groups and the agreement with ICU criteria. There were 49 patients in treatment groups and 54 patients in non-treatment groups. There were more cases of solid organ transplantation (P = .003), immunosuppressive therapy (P < .001) and bacterial viral coinfection (P = .048) in the treatment group compared to nontreatment group. There was no statistically significant difference in mortality, the use of ventilator, and septic shock between the two groups. The agreement rate between the putative group and treatment was low (59.2%). There was no statistically significant difference in outcome between the putative and colonization groups according to the ICU criteria in each group. The treatment of IPA based on the symptom, radiologic finding and galactomannan test did not showed the better outcome. Also, the treatment based on the ICU criteria didn't show the difference of outcome. The new criteria for diagnosis of IPA in critically ill patients are needed.

Topics: Aged; Bronchoalveolar Lavage Fluid; Critical Illness; Female; Galactose; Humans; Immunosuppressive Agents; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Organ Transplantation; Radiology; Retrospective Studies

Topics: Biomarkers; Critical Illness; Female; Galactose; Humans; Influenza, Human; Invasive Pulmonary Aspergillosis; Male; Mannans

To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO). A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm. One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4-73.4). Ten (7%) patients had putative IPA and nine (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. The median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively. Immunosuppression and influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Critical Illness; Echinocandins; Extracorporeal Membrane Oxygenation; Female; Galactose; Humans; Immunocompromised Host; Influenza, Human; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Micafungin; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome; Voriconazole; Young Adult

Invasive pulmonary aspergillosis (IPA) is an emerging and life-threatening infectious disease in patients admitted to the intensive care unit (ICU). Most diagnostic studies are conducted in hematological patients and results cannot readily be transferred to ICU patients lacking classical host factors. In a multicenter, prospective clinical trial including 44 ICU patients, hematological (n = 14) and non-hematological patients (n = 30), concurrent serum and bronchoalveolar lavage (BAL) samples were analyzed by conventional culture, galactomannan (GM), 1-3-beta-D-glucan (BDG) as well as an Aspergillus specific nested polymerase chain reaction (PCR). Nine patients (20%) had putative IPA according to AspICU classification. GM and PCR showed superior performance in BAL with sensitivity/specificity of 56%/94% and 44%/94% compared to 33%/97% and 11%/94% in serum. Despite better sensitivity of 89%, BDG showed poor specificity of only 31% (BAL) and 26% (serum). Combination of GM and PCR (BAL) with BDG (serum) resulted in 100% sensitivity, but also reduced specificity to 23%. Whereas mean GM levels were significantly higher in hematological patients BDG and PCR did not differ between hematological and non-hematological patients. Under present clinical conditions test combinations integrating both BAL and blood samples are advantageous. BDG might best serve as possible indicator for ruling out IPA.. ClinicalTrials.gov Identifier: NCT01695499. First posted: September 28, 2012, last update posted: May 8, 2017.

Topics: Adult; Aged; Aged, 80 and over; Aspergillus; beta-Glucans; Bronchoalveolar Lavage Fluid; Critical Illness; Diagnostic Tests, Routine; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Pilot Projects; Polymerase Chain Reaction; Prospective Studies; Young Adult

Pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. This organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. We report an unusual case of pulmonary P. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of Aspergillus fumigatus and Aspergillus terreus with ARDS. This case highlights the importance of a high index of suspicion for superimposed fungal infections in patients who are critically ill and immunocompromised. Uncommon fungal pathogens should be considered in the differential diagnosis of respiratory failure, especially if diagnostic markers such as galactomannan (from BAL and serum) or 1,3-beta-D-glucan are elevated. Further diagnostic interventions are warranted when insufficient clinical improvement is observed to prevent treatment failure and adverse outcomes.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Clarithromycin; Coinfection; Critical Illness; Extracorporeal Membrane Oxygenation; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Linezolid; Male; Mannans; Meropenem; Pneumonia; Pseudallescheria; Severe Acute Respiratory Syndrome; Thienamycins; Transplant Recipients; Voriconazole

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in critically ill patients with hematological malignancies. New diagnosis strategies include the noninvasive biomarkers 1,3-beta-D-glucan (BDG) and serum galactomannan (GM).. For early detection of IPA, we compared BDG Fungitell assay with GM Platelia assay.. Twenty-two out of 30 patients (74 %) had elevated BDG levels (mean 306 pg/ml) beyond the cutoff of 80 pg/ml. GM levels were elevated in only 3 patients (10 %) over the ODI cutoff of >0.5. Following the BDG/GM and microbiological findings, 10 (34 %) cases were classified as probable IPA and 12 (40 %) as possible IPA. Eight (26 %) were classified as no IPA. An overall sensitivity of 90 % (95 % CI 86-96 %) and specificity of 85 % (95 % CI 79-86 %) was found for the BDG Fungitell assay in IPA. In contrast, an overall sensitivity of 30 % (95 % CI 26-38 %) and specificity of 98 % (95 % CI 94-100 %) was found for the GM Platelia assay. A false-negative rate of 70 % for probable IPA and 85 % for probable/possible IPA was detected for GM. The false-negative rate for BDG was 0 % in cases of probable IPA and 45 % in cases of possible cases.. BDG is a sensitive marker for patients' surveillance at risk of IPA. In patients with hematological malignancies and septic shock, early diagnosis of IPA might be significantly improved by BDG compared to GM, also considering that BDG has the advantage of detecting fungal diseases other than IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; beta-Glucans; Critical Illness; Diagnostic Tests, Routine; Early Diagnosis; Female; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Proteoglycans; Sensitivity and Specificity; Serum; Shock, Septic; Young Adult

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients.. Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU.. In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay.. 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; APACHE; Aspergillus; Autoimmune Diseases; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Critical Illness; Early Diagnosis; Female; Galactose; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Intensive Care Units; Invasive Pulmonary Aspergillosis; Length of Stay; Male; Mannans; Middle Aged; Mortality; Neoplasms; Neutropenia; Organ Dysfunction Scores; Organ Transplantation; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Sensitivity and Specificity; Young Adult

Topics: Aspergillus; beta-Glucans; Critical Illness; Galactose; Glucans; Humans; Mannans

Critically ill chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ICU) due to respiratory failure are at particularly high risk of Aspergillus infection. The serum galactomannan index (GMI) has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis (IPA) in classical immunocompromised patients. However, the prognostic value of serum GMI in critically ill COPD patients needs evaluation. The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.. In this single-center prospective cohort study, serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients' discharge or death. Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission. Univariate analysis and survival analysis were tested in these two groups.. One hundred and fifty-three critically ill COPD patients were included and were divided into survival group (106 cases) and non-survival group (47 cases) according to their outcome. Univariate analysis showed that the highest GMI level during the first week after admission (GMI-high 1st week) was statistically different between the two groups. Independent prognostic factors for poor outcome in severe COPD patients were: GMI-high 1st week >0.5 (RR: 4.04, 95% CI: 2.17-7.51) combined with accumulative dosage of corticosteroids >216 mg before the RICU admission (RR: 2.25, 95% CI: 1.11-4.56) and clearance of creatinine (Ccr) ≤ 64.31 ml/min (RR: 2.48, 95% CI: 1.22 ± 5.07).. The positive GMI-high 1st week (>0.5) combined with an accumulative dosage of corticosteroids >216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

Topics: Aged; Aged, 80 and over; Critical Illness; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive

Topics: Antifungal Agents; Antigens; Biomarkers; Critical Illness; Early Diagnosis; Galactose; Humans; Immunocompromised Host; Immunologic Techniques; Incidence; Invasive Pulmonary Aspergillosis; Mannans; Opportunistic Infections

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Critical Illness; Female; Galactose; Humans; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Proteoglycans; ROC Curve; Sepsis

Critically ill chronic obstructive pulmonary disease (COPD) patients are at particular risk of invasive pulmonary aspergillosis (IPA). Our aims were to determine whether bronchoalveolar lavage fluid (BALF) galactomannan (GM) has a higher sensitivity and specificity than serum GM or lower respiratory tract (LRT) sample culture. Furthermore, we aimed to investigate what the optimal cut-off value would be for BALF GM.. In this prospective single-center study, BALF and serum samples were collected from critically ill COPD patients on the first day of their intensive care unit admission.. Of 50 critically ill COPD patients admitted, BALF and serum samples were collected in 34 patients. According to the receiver operating characteristics (ROC) curve, an optical density (OD) ratio of 0.8 was chosen as the cut-off value for GM in BALF. Compared to serum GM and LRT Aspergillus isolation, BALF GM yield a better sensitivity, specificity, positive and negative predictive values of 88.9%, 100%, 100% and 94.4%, respectively. Areas under the ROC curve were 0.912 (95%CI, 0.733 to 0.985) for BALF GM, and 0.879 (95%CI, 0.691 to 0.972) for serum GM results from the first day of ICU admission. Pairwise comparison of ROC curves showed P = 0.738. The OD ratio of BALF GM in IPA patients were significantly higher than those of non-IPA patients (2.88 ± 2.09 versus 0.49 ± 0.19, P = 0.009), and the OD ratio of BALF GM was significantly higher than serum GM in IPA patients (2.88 ± 2.09 versus 0.87 ± 0.47, P = 0.023). Positive BALF GM was seen earlier than LRT secretion culture (1 day versus 3.8 days).. Compared to serum GM and LRT Aspergillus isolation, BALF GM seems to have a better sensitivity in the diagnosis of IPA in critically ill COPD patients. The ROC curve suggests a possible cut-off value of 0.8 for GM from BALF specimens in critically ill COPD patients.

Topics: Aged; Aged, 80 and over; APACHE; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Critical Illness; Enzyme-Linked Immunosorbent Assay; Female; Galactose; Hospital Mortality; Humans; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Mycology; Predictive Value of Tests; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)-β-D-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94-1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74-0.96) and 0.815 (95% CI, 0.66-0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1-10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

Topics: Adult; Aged; beta-Glucans; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prospective Studies; Proteoglycans; ROC Curve; Serum

Critically ill chronic obstructive pulmonary disease (COPD) patients who are admitted to intensive care units (ICU) are at particular risk for invasive pulmonary aspergillosis (IPA). The objective of this investigation was to assess the value of consecutive galactomannan (GM) tests in determining the diagnosis and prognosis of IPA in this patient population. We studied 90 critically ill COPD patients admitted to our ICU between February 2007 and November 2009. Two consecutive serum GM tests were done on the first and fourth days of their ICU admissions. Patients were classified as proven IPA (n = 1), probable IPA (n = 18), or non-IPA (n = 71). The sensitivities, specificities, and positive and negative predictive values of GM test results for (i) the first test, (ii) the second test, (iii) at least one positive of two consecutive tests and (iv) two positive consecutive GM tests were, respectively, 57.9%/64.7%/70.6%/47.1%; 87.3%/84.6%/80.8%/94.2%; 55.0%/57.9%/54.5%/72.7%; and 88.6%/88.0%/89.4%/84.5%. The mortality values of IPA patients with (i) a positive first GM test, (ii) at least one of two tests positive, and (iii) both tests positive were (a) 81.8% (9/11), (b) 83.3% (10/12), and (c) 72.7% (8/11), respectively. These results indicate that at least one positive result of two consecutive GM tests appears to be useful in the diagnosis of IPA in critically ill COPD patients in an ICU. In addition, positive serum GM results combined with the isolation of Aspergillus from respiratory samples may be a potential marker of high mortality.

Topics: Aspergillus; Critical Illness; Galactose; Humans; Intensive Care Units; Invasive Pulmonary Aspergillosis; Mannans; Opportunistic Infections; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity; Sputum

To evaluate the usefulness of serum galactomannan (GM) for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients.. Study was conducted between February 2007 and July 2008. Included patients on admission ICU who suffer from suspected IPA. GM test and culture were collected 2 weekly. Clinical feature, mycological evidence and optical density index (ODI) were noted. Clinically invasive fungal infection (IFI) were defined proven, probable and possible. The patients were classified into neutropenia, non-neutropenia and treated with immunosuppressive agents, non-neutropenia and non-immunosuppressive agents. To compared of the sensitivity and specificity of GM in different patients.. 94 patients were included, 4 patients were proven, 29 patients were probable, 34 patients were possible IFI, 27 patients were non-IPA. The positive rate of the GM was 31.9% (30/94). The sensitivity and specificity of GM in proven cases and probable cases are 66.7% and 92.6%. GM assay tended to become positive earlier than the culture 2 - 10 (5.33 +/- 2.17) d. We found that differences in patient diagnosis and selection might account for the disparities seen for positive rate for the GM test. There was positive in three of the four patients with proven, the positive rate of GM was 65.5% for probable cases, for possible cases was 17.6%, for non-IPA cases was 7.4% (P = 0.001). For patient with neutropenia, treated with immunosuppressive agents and without immunosuppressive agents, the positive rate of GM was 52.9% vs 41.7% vs 34.6% (P = 0.015); the sensitivity was 80.0% vs 70.0% vs 53.8% (P = 0.011), the ODI was 1.365 (0.582 - 6.736) vs 1.123 (0.623 - 6.868) vs 0.554 (0.522 - 0.823), P = 0.005, respectively.. These results show that GM test is useful for early diagnosis IPA in critically ill patients. Differences in patient selection and diagnosis might account for the disparities seen for positive rate and sensitivity for the GM test. It has been higher sensitivity and ODI in the patient treated by immunosuppressive agents.

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prospective Studies; Sensitivity and Specificity