Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches

Jenks, Jeffrey D.; Nam, Hannah; Hoenigl, Martin

doi:10.1111/myc.13274

Cited by 63 publications

(53 citation statements)

References 112 publications

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“…Reported CAPA prevalence rates vary widely between different studies (3% - 33%)[ [12] , [13] , [14] , [15] , [16] ]. Several factors may explain the wide variation of CAPA rates including differences in awareness and local diagnostic strategies (e.g., bronchoscopies not done[ 17 ]), as well as various different criteria applied for definition of aspergillosis in COVID-19 patients[ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology

Prattes

Wauters

Giacobbe

et al. 2022

Clinical Microbiology and Infection

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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.

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Section: Introductionmentioning

confidence: 99%

Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology

Prattes

Wauters

Giacobbe

et al. 2022

Clinical Microbiology and Infection

Self Cite

172

210

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“…Diagnosis of CAPA is challenging in patients with COVID-19-associated ARDS, as clinical picture and radiological findings of CAPA resemble those of severe COVID-19 [15,16], and blood tests lack sensitivity due to the primarily airway invasive growth of Aspergillus in non-neutropenic patients [15][16][17]. Testing of bronchoalveolar lavage (BAL) with fungal culture, galactomannan (GM), Aspergillus polymerase chain reaction (PCR), or the Aspergillus GM lateral flow assay (LFA) is therefore preferred [18,19], but due to the presumed risk of COVID-19 transmission through bronchoscopies, sampling of the primary infection site is still not performed consistently across ICUs.…”

Section: Introductionmentioning

confidence: 99%

Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study

et al. 2021

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Background Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. Methods In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. Results We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2–9.7) in the MAFP group and 17.5% (95% CI 9.6–31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01–0.63; p = 0.017). Conclusion In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

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“… 2 , 5 , 6 Furthermore, the sensitivity of GM from blood declines in those on antifungal prophylaxis or treatment. 5 , 7 , 8 Other molecular tests such as polymerase chain reaction lack standardisation, have variable diagnostic performance across studies and settings, with declining performance in those on mould‐active prophylaxis. 9 Thus, there is a need for improved diagnostics from blood for IA.…”

Section: Introductionmentioning

confidence: 99%

Serum Lateral Flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two‐centre mixed cohort study

Hoenigl

Egger

Boyer

et al. 2021

Mycoses

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Background Detection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non‐neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients. Methods We performed a retrospective two‐centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same‐sample GM was calculated using Spearman correlation analysis and kappa statistics. Results In total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus‐associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non‐classifiable (n = 94). At a 0.5 ODI cut‐off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p < .0001). Kappa was 0.611 when both LFA and GM were used with a 0.5 ODI cut‐off, showing substantial agreement (p < .001). Discussion The LFA with digital read out from serum showed good performance for the diagnosis of probable/proven aspergillosis, with substantial agreement to GM from serum. Like the LFA from BALF, the LFA from serum may serve as a more rapid test compared to conventional GM, particularly in settings where GM is not readily available.

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Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches

Cited by 63 publications

References 112 publications

Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology

Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology

Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study

Serum Lateral Flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two‐centre mixed cohort study

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