Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report

Meijer, Eelco F. J.; Dofferhoff, Anton S M; Hoiting, Oscar; Buil, Jochem B.; Meis, Jacques F.

doi:10.3390/jof6020079

Cited by 91 publications

(98 citation statements)

References 40 publications

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“…The development of CAPA was fairly rapid, with a median of 6 days and range of 3-28 days after ICU admission [47,52]. Moreover, two additional CAPA cases have been reported from Germany [61] and single cases have also been reported from the Netherlands [62], Austria [60], Italy [59], Australia [63], and France [57,58] (Table 1). Among 35 CAPA cases reported to date, there were a total of 5 proven cases [52,59].…”

Section: Capa Prevalencementioning

confidence: 97%

“…Since azole resistance can be associated with a higher mortality rate when compared to patients infected with azole susceptible A. fumigatus isolates, it is of paramount importance to use antifungal susceptibility testing to inform targeted antifungal treatment, especially in regions with high azole resistance [77]. Azole-resistant A. fumigatus isolates were also persistently recovered from tracheal aspirates during the course of azole treatment in the most recent study from the Netherlands implicated a CAPA case for whom [62]. The azole-resistant A. fumigatus isolate (itraconazole, voriconazole, and posaconazole MICs were 16, 2, and 0.5 µg/mL, respectively) harbored a well-known mutation, TR34/L98H [62], presumed to have been acquired from the environment [77].…”

Section: Capa Prevalencementioning

confidence: 99%

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COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment

Arastehfar

Carvalho

Veerdonk

et al. 2020

JoF

323

404

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Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.

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Section: Capa Prevalencementioning

confidence: 97%

Section: Capa Prevalencementioning

confidence: 99%

COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment

Arastehfar

Carvalho

Veerdonk

et al. 2020

JoF

323

404

View full text Add to dashboard Cite

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“…Only seven cases reported susceptibility results based on either phenotypic testing and/or the detection of common mutations associated with triazole resistance using molecular techniques. Three cases were reported to be caused by a triazole-resistant A. fumigatus, all of which were confirmed to have the cyp51A TR 34 L98H mutation [ 16 , 21 , 23 ]. Knowledge of the local epidemiology of triazole resistance is important to help guide the choice of therapy while awaiting susceptibility results.…”

Section: Antifungal Treatment Strategies For Capamentioning

confidence: 99%

“…With the global spread of COVID-19, as of 30 June 2020, 38 cases of CAPA have been reported. [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Here, we review these cases of CAPA so as to highlight the diagnostic and therapeutic challenges posed by this novel fungal co-infection.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges

Mohamed

Rogers

Talento

2020

JoF

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Aspergillus co-infection in patients with severe coronavirus disease 2019 (COVID-19) pneumonia, leading to acute respiratory distress syndrome, has recently been reported. To date, 38 cases have been reported, with other cases most likely undiagnosed mainly due to a lack of clinical awareness and diagnostic screening. Importantly, there is currently no agreed case definition of COVID-19 associated invasive pulmonary aspergillosis (CAPA) that could aid in the early detection of this co-infection. Additionally, with the global emergence of triazole resistance, we emphasize the importance of antifungal susceptibility testing in order to ensure appropriate antifungal therapy. Herein is a review of 38 published CAPA cases, which highlights the diagnostic and therapeutic challenges posed by this novel fungal co-infection.

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“…The last patient was treated in a tertiary center in the Netherlands [ 34 ] and had no known history of exposure to azoles. Her tracheal aspirate cultures upon ICU admission grew pan-sensitive A. fumigatus and the patient was initially treated with voriconazole.…”

Section: Microbiologymentioning

confidence: 99%

Invasive Pulmonary Aspergillosis in Patients with SARS-CoV-2 Infection: A Systematic Review of the Literature

et al. 2020

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In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

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Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report

Cited by 91 publications

References 40 publications

COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment

COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment

COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges

Invasive Pulmonary Aspergillosis in Patients with SARS-CoV-2 Infection: A Systematic Review of the Literature

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