Invasive pulmonary aspergillosis complicating COVID-19 in the ICU - A case report.

It is not yet known, if critically ill COVID-19 patients are prone to fungal infections. We report a 69-year-old patient without typical risk factors for invasive pulmonary aspergillosis (IPA), who developed IPA two weeks after onset of symptoms. Our report shows that IPA may occur in critically ill COVID-19 patients

Questioning the 14-day dogma in candidemia treatment duration

The growing threat of antimicrobial resistance (AMR) is a global concern. With AMR directly causing 1.27 million deaths in 2019 and projections of up to 10 million annual deaths by 2050, optimising infectious disease treatments is imperative. Prudent antimicrobial use, including treatment duration, can mitigate AMR emergence. This is particularly critical in candidemia, a severe condition with a 45% crude mortality rate, as the 14-day minimum treatment period has not been challenged in randomised comparison. A comprehensive literature search was conducted in August 2023, revealing seven original articles and two case series discussing treatment durations of less than 14 days for candidemia. No interventional trials or prospective observational studies assessing shorter durations were found. Historical studies showed varying candidemia treatment durations, questioning the current 14-day minimum recommendation. Recent research observed no significant survival differences between patients receiving shorter or longer treatment, emphasising the need for evidence-based guidance. Treatment duration reduction post-blood culture clearance could decrease exposure to antifungal drugs, limiting selection pressure, especially in the context of emerging multiresistant Candida species. Candidemia's complexity, emerging resistance and potential for shorter in-hospital stays underscore the urgency of refining treatment strategies. Evidence-driven candidemia treatment durations are imperative to balance efficacy with resistance prevention and ensure the longevity of antifungal therapies. Further research and clinical trials are needed to establish evidence-based guidelines for candidemia treatment duration

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

Background1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values.MethodsBDG was determined in 346 samples from 50 patients undergoing laparoscopic (24) or open (26) intestinal surgery at the following time points: after insertion of arterial but before skin incision, after skin incision but before dissection of the intestinal mucosa, after completion of anastomosis, after completion of skin sutures, in the evening after surgery, day 2 after surgery, 4-5 days after surgery.ResultsBDG was positive (ie, concentration ≥80 pg/mL) in 54% to 61% of patients during laparoscopic and open surgery (highest rates after completion of skin sutures). BDG was still positive in 12% (open) to 17% (laparoscopic) of patients without any suspected or proven fungal infection or anastomotic leakage 4-5 days after surgery. After completion of gut anastomosis, the BDG increase was higher in open compared with laparoscopic intestinal surgery.ConclusionsThe value of positive BDG tests in the perioperative setting up to 5 days postsurgery seems to be limited due to BDG elevations from intestinal surgical procedures

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

Evaluation of Galactomannan Testing, the Aspergillus-Specific Lateral-Flow Device Test and Levels of Cytokines in Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

Background: Diagnosis of chronic pulmonary aspergillosis (CPA) is challenging. Symptoms are unspecific or missing, radiological findings are variable and proof of mycological evidence is limited by the accuracy of diagnostic tests. The goal of this study was to investigate diagnostic performance of galactomannan (GM), the newly formatted Aspergillus-specific lateral-flow-device test (LFD), and a number of cytokines in bronchoalveolar lavage fluid (BALF) samples obtained from patients with CPA, patients with respiratory disorders without CPA and healthy individuals.Methods: Patients with CPA (n = 27) and controls (n = 27 with underlying respiratory diseases but without CPA, and n = 27 healthy volunteers) were recruited at the Medical University of Graz, Austria and the Research Center Borstel, Germany between 2010 and 2018. GM, LFD and cytokine testing was performed retrospectively at the Research Center Borstel.Results: Sensitivity and specificity of GM testing from BALF with a cut off level of ≥0.5 optical density index (ODI) was 41 and 100% and 30 and 100% with a cut off level of ≥1.0 ODI. ROC curve analysis showed an AUC 0.718 (95% CI 0.581–0.855) for GM for differentiating CPA patients to patients with other respiratory diseases without CPA. The LFD resulted positive in only three patients with CPA (7%) and was highly specific. CPA patients did not differ significantly in the BALF cytokine profile compared to patients with respiratory disorders without CPA, but showed significant higher values for IFN-γ, IL-1b, IL-6, IL-8, and TNF-α compared to healthy individuals.Conclusion: Both GM and LFD showed insufficient performance for diagnosing CPA, with sensitivities of BALF GM below 50%, and sensitivity of the LFD below 10%. The high specificities may, however, result in a high positive predictive value and thereby help to identify semi-invasive or invasive disease

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

Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome