Objectives Coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome. Methods The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centers from nine different countries to assess epidemiology, risk factors, and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions. Results A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) patients with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31) after ICU admission predominantly in older patients [adjusted hazard ratio (aHR) 1.04 per year; 95%CI 1.02-1.06] with any form of invasive respiratory support (HR 3.4; 95%CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95%CI 1.41-4.25). Median prevalence of CAPA per center was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar p<0.001 ) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR=2.14; 95%CI: 1.59-2.87, p<=0.001 ). Conclusion Prevalence of CAPA varied between centers. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.

Dear Editor,Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure caused by SARS-CoV-2 [1-3]. A cornerstone in CAPA diagnosis is microbiology, including culture from lower respiratory tract samples, and bronchoalveolar lavage fluid (BALF) galactomannan (GM) [4,5].We performed a multinational cohort study including 20 centers in 9 countries with the aim to evaluate diagnostic approaches and treatment of CAPA as well as CAPA prevalence. All participating centers were invited to provide data on diagnostic work-up, treatment and outcome on prospective cohorts of consecutive COVID-19 ICU patients (inclusion criteria: SARS-CoV-2-positive polymerase chain reaction, admission to intensive care unit (ICU) due to respiratory failure) with and without CAPA via an online case report form between 03/2020 and 05/2021. Cases were then classified according to the 2020 ECMM/ISHAM consensus criteria [4]. The study protocol was approved by the Medical University of

The increasing incidence of extensively drug-resistant (XDR) Mycobacterium tuberculosis in high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDR M. tuberculosis strains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the "hot-spot" regions of rpoB, katG, inhA, ahpC, gyrA, gyrB, and rrs genes in 50 XDR M. tuberculosis strains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDR M. tuberculosis strains would be undetected if only these common hot-spot regions were tested. The frequencies of resistanceconferring mutations were found to be comparable among all XDR M. tuberculosis strain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDR M. tuberculosis strains.

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The incidence of chronic pulmonary aspergillosis (CPA) is especially increasing in high tuberculosis (TB) burden countries. Despite a high estimated CPA burden in Pakistan, actual data on CPA are not available. The aim of the current study is to determine the underlying conditions and clinical spectrum of CPA at a tertiary care hospital in Karachi, Pakistan. This is a retrospective chart review study in patients admitted with CPA from January 2012 to December 2017. A total of 67 patients were identified during the study period. Mean age of CPA patients was 45.9 ± 15 years, 44 (65.7%) were male and 19 (28.4%) had diabetes. The most common type of CPA was simple aspergilloma (49.2%) followed by chronic cavitary pulmonary aspergillosis (CCPA) (44.7%). TB was the underlying cause of CPA in 58 (86.6%) patients followed by bronchiectasis caused by allergic bronchopulmonary aspergillosis (ABPA) 8 (11.9%). Aspergillus flavus was identified in 17 (47.2%), followed by A. fumigatus in 13 (36.1%) CPA patients. Isolation of multiple Aspergillus species was found in 10 (25.6%) patients. Itraconazole was given in 27 (40.3%) patients and a combination therapy of itraconazole and surgery was given in 21 (31.34%) patients. We found aspergilloma and CCPA as the most prevalent forms of CPA in our setting. Further large prospective studies using Aspergillus specific immunoglobulin G (IgG) antibodies testing are required for better understanding of CPA in Pakistan.