COVID-19 associated Pulmonary Aspergillosis in Patients Admitted to the Intensive Care Unit: Impact of Antifungal Prophylaxis.

Early after the beginning of the coronavirus disease 2019 (COVID-19)-pandemic, it was observed that critically ill patients in the intensive care unit (ICU) were susceptible to developing secondary fungal infections, particularly COVID-19 associated pulmonary aspergillosis (CAPA). Here we report our local experience on the impact of mold active antifungal prophylaxis on CAPA occurrence in critically ill COVID-19 patients. This is a monocentric, prospective cohort study including all consecutive patients with COVID-19 associated acute respiratory failure who were admitted to our local medical ICU. Based on the treating physician's discretion, patients may have received antifungal prophylaxis or not. All patients were retrospectively characterized as having CAPA according to the 2020 ECMM/ISHAM consensus definitions. Seventy-seven patients were admitted to our medical ICU during April 2020 and May 2021 and included in the study. The majority of patients received invasive-mechanical ventilation (61%). Fifty-three patients (68.8%) received posaconazole prophylaxis. Six cases of probable CAPA were diagnosed within clinical routine management. All six cases were diagnosed in the non-prophylaxis group. The incidence of CAPA in the overall study cohort was 0.57 events per 100 ICU days and 2.20 events per 100 ICU days in the non-prophylaxis group. No difference of cumulative 84-days survival could be observed between the two groups (p = 0.115). In this monocentric cohort, application of posaconazole prophylaxis in patients with COVID-19 associated respiratory failure did significantly reduce the rate of CAPA.

Vinorelbine as substitute for vincristine in patients with diffuse large B cell lymphoma and vincristine-induced neuropathy.

BACKGROUND: A combination of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard first-line therapy for diffuse large B cell lymphoma (DLBCL), the most common aggressive lymphoma in adults. One of the major adverse effects of this regimen is vincristine-induced polyneuropathy which leads to discontinuation of vincristine in up to 30% of DLBCL-patients. Dose reduction of vincristine might worsen treatment outcomes of DLBCL but identification of treatment alternatives for patients exhibiting peripheral neuropathy during R-CHOP is an unmet need in hematology. METHODS: In this retrospective cohort study, comprising 987 patients with de novo DLBCL, we delineated the role of vinorelbine as a substitute for vincristine in R-CHOP by measuring improvements in neuropathy and outcome variables. RESULTS: Five-year overall survival (OS) and progression-free survival (PFS) were 72.6% and 63.1% in patients who received regular doses of vincristine, as compared to 60.6% and 51.7% in patients who received reduced doses of vincristine (p = 0.022 and p = 0.003, respectively). Of 199 patients who switched to vinorelbine, the majority experienced an improvement of neuropathy Furthermore, vinorelbine-switched patients showed favorable oncologic outcomes. CONCLUSION: Replacement of vincristine by vinorelbine due to neuropathy is effective and safe, and results in a significant improvement in neuropathy as compared to treatment with R-CHOP.

Point-of-care testing for viral-associated pulmonary aspergillosis.

INTRODUCTION: Over the last years, severe respiratory viral infections, particularly those caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the influenza virus, have emerged as risk factor for viral-associated pulmonary aspergillosis (VAPA) among critically ill patients. Delays in diagnosis of VAPA are associated with increased mortality. Point-of-care-tests may play an important role in earlier diagnosis of VAPA and thus improve patient outcomes. AREAS COVERED: The following review will give an update on point-of-care tests for VAPA, analyzing performances in respiratory and blood specimens. EXPERT OPINION: Point-of-care tests have emerged, and particularly the IMMY Aspergillus galactomannan lateral flow assay (LFA) shows performances comparable to the galactomannan ELISA for diagnosis of VAPA. Notably, nearly all evaluations of POC tests for VAPA have been performed in COVID-19 patients, with very limited data in influenza patients. For early diagnosis of COVID associated pulmonary aspergillosis (CAPA), the LFA has shown promising performances in respiratory samples, particularly in bronchoalveolar lavage fluid, and may thereby help in improving patient outcomes. In contrast, serum LFA testing may not be useful for early diagnosis of disease, except in cases with invasive tracheobronchial aspergillosis.

Pathogen Detection by Metagenomic Next-Generation Sequencing During Neutropenic Fever in Patients With Hematological Malignancies.

Background: Febrile neutropenia (FN) after chemotherapy is a major cause of morbidity during cancer treatment. The performance of metagenomic next-generation sequencing (mNGS) of circulating cell-free deoxyribonucleic acid from plasma may be superior to blood culture (BC) diagnostics for identification of causative pathogens. The aim of this study was to validate mNGS (DISQVER test) for the detection of pathogens in hematologic patients with FN. Methods: We collected paired whole blood specimens from central venous catheter and peripheral vein during FN for BC and mNGS testing. We repeated paired sampling at the earliest after 3 days of fever, which was defined as 1 FN episode. All clinical data were retrospectively reviewed by an infectious disease expert panel. We calculated percent positive agreement (PPA), percent negative agreement (PNA), percent overall agreement (POA), and sensitivity and specificity. Results: We analyzed a total of 98 unselected FN episodes in 61 patients who developed predominantly FN after conditioning therapy for allogeneic (n = 22) or autologous (n = 21) hematopoietic stem cell transplantation. Success rate of mNGS was 99% (97 of 98). Positivity rate of mNGS was 43% (42 of 97) overall and 32% (31 of 97) excluding viruses compared to 14% (14 of 98) in BC. The PPA, PNA, and POA between mNGS and BC were 84.6% (95% confidence interval [CI], 54.6% to 98.1%), 63.1% (95% CI, 51.9% to 73.4%), and 66% (95% CI, 55.7% to 75.3%), respectively. Sensitivity for bacteria or fungi was 40% (95% CI, 28.0% to 52.9%) and 18.5% (95% CI, 9.9% to 30.0%), respectively. Conclusions: Pathogen detection by mNGS (DISQVER) during unselected FN episodes shows 2-fold higher sensitivity and a broader pathogen spectrum than BC.