Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients

Introduction: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. Methods: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Results: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. Conclusion: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. Trial registration: ClinicalTrials.gov NCT02058316. Registered 20 January 2014

Point of Care Testing for the Diagnosis of Fungal Infections: Are We There Yet?

Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay)

Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies

Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.

Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases.

RationaleInvasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases.ObjectivesWe compared the diagnostic performances of galactomannan, 1,3-β-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases.MethodsWe analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases.Measurements and main resultsThirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), β-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14).ConclusionsProbable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of β-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316)

Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria.

PurposeThe objective of this study was to compare epidemiology, causative pathogens, outcome, and levels of laboratory markers of inflammation of community-onset (i.e. community-acquired and healthcare-associated) and hospital-acquired bloodstream infection (BSI) in South-East Austria.MethodsIn this prospective cohort study, 672 patients fulfilling criteria of systemic inflammatory response syndrome with positive peripheral blood cultures (277 community-onset [192 community-acquired, 85 healthcare-associated BSI], 395 hospital-acquired) were enrolled at the Medical University of Graz, Austria from 2011 throughout 2012. Clinical, microbiological, demographic as well as outcome and laboratory data was collected.ResultsEscherichia coli followed by Staphylococcus aureus were the most frequently isolated pathogens. While Streptococcus spp. and Escherichia coli were isolated more frequently in patients with community-onset BSI, Enterococcus spp., Candida spp., Pseudomonas spp., Enterobacter spp., and coagulase-negative staphylococci were isolated more frequently among those with hospital-acquired BSI. With regard to the outcome, 30-day (82/395 vs. 31/277; p = 0.001) and 90-day mortality (106/395 vs. 35/277; p<0.001) was significantly higher among patients with hospital-acquired BSI even though these patients were significantly younger. Also, hospital-acquired BSI remained a significant predictor of mortality in multivariable analysis. At the time the blood cultures were drawn, patients with community-onset BSI had significantly higher leukocyte counts, neutrophil-leucocyte ratios as well as C-reactive protein, procalcitonin, interleukin-6 and serum creatinine levels when compared to those with hospital-acquired BSI. Patients with healthcare-associated BSI presented with significantly higher PCT and creatinine levels than those with community-acquired BSI.ConclusionsHospital-acquired BSI was associated with significantly higher 30- and 90-day mortality rates. Hospital-acquired BSI therefore poses an important target for the most aggressive strategies for prevention and infection control

Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria.

The objective of this study was to compare epidemiology, causative pathogens, outcome, and levels of laboratory markers of inflammation of community-onset (i.e. community-acquired and healthcare-associated) and hospital-acquired bloodstream infection (BSI) in South-East Austria.In this prospective cohort study, 672 patients fulfilling criteria of systemic inflammatory response syndrome with positive peripheral blood cultures (277 community-onset [192 community-acquired, 85 healthcare-associated BSI], 395 hospital-acquired) were enrolled at the Medical University of Graz, Austria from 2011 throughout 2012. Clinical, microbiological, demographic as well as outcome and laboratory data was collected.Escherichia coli followed by Staphylococcus aureus were the most frequently isolated pathogens. While Streptococcus spp. and Escherichia coli were isolated more frequently in patients with community-onset BSI, Enterococcus spp., Candida spp., Pseudomonas spp., Enterobacter spp., and coagulase-negative staphylococci were isolated more frequently among those with hospital-acquired BSI. With regard to the outcome, 30-day (82/395 vs. 31/277; p = 0.001) and 90-day mortality (106/395 vs. 35/277; p<0.001) was significantly higher among patients with hospital-acquired BSI even though these patients were significantly younger. Also, hospital-acquired BSI remained a significant predictor of mortality in multivariable analysis. At the time the blood cultures were drawn, patients with community-onset BSI had significantly higher leukocyte counts, neutrophil-leucocyte ratios as well as C-reactive protein, procalcitonin, interleukin-6 and serum creatinine levels when compared to those with hospital-acquired BSI. Patients with healthcare-associated BSI presented with significantly higher PCT and creatinine levels than those with community-acquired BSI.Hospital-acquired BSI was associated with significantly higher 30- and 90-day mortality rates. Hospital-acquired BSI therefore poses an important target for the most aggressive strategies for prevention and infection control

Galactomannan testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples for diagnosis of invasive aspergillosis.

In recent years galactomannan antigen testing (GM) and also Aspergillus PCR have become increasingly important for diagnosis of invasive aspergillosis (IA). Whether or not these tests need to be performed with bronchoalveolar lavage fluid (BALF; i.e., primary site of infection), or testing of blood samples is sufficient, remains, however, a matter of debate. We evaluated the diagnostic performance of GM ELISA, and Aspergillus PCR by using BALF samples and blood samples obtained at the same day from a total of 53 immunocompromised patients (16 with probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria; 38 patients with hematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital). Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and 12/16 (75%) of patients with probable/proven IA received mold-active antifungal prophylaxis/therapy at the time of the BALF procedure. Sensitivities of GM and Aspergillus PCR were 38% and 44% in BALF, and 31% and 0% in blood, respectively. Best sensitivity (75%) for detecting proven/probable IA was achieved when BALF Aspergillus PCR, BALF GM (&gt;1.0 ODI), BALF-culture and serum-GM (&gt;0.5 ODI) were combined (specificity 95%). In conclusion, sensitivities of the evaluated diagnostic tests-when interpreted on their own-were low in BALF and even lower in blood, sensitivities increased markedly when diagnostic tests were combined