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Journal of Fungi (Basel, Switzerland) Apr 2021Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with... (Review)
Review
BACKGROUND
Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients.
METHODS
A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate.
RESULTS
A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.
PubMed: 33922773
DOI: 10.3390/jof7050327 -
Mycoses Sep 2021COVID-19-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this... (Meta-Analysis)
Meta-Analysis
COVID-19-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this systematic review and meta-analysis, we aimed to determine the incidence and mortality of CAPA in critically ill patients with COVID-19 to improve guidance on surveillance and prognostication. Observational studies reporting COVID-19-associated pulmonary aspergillosis were searched with PubMed and Embase databases, followed by an additional manual search in April 2021. We performed a one-group meta-analysis on the incidence and mortality of CAPA using a random-effect model. We identified 28 observational studies with a total of 3148 patients to be included in the meta-analysis. Among the 28 studies, 23 were conducted in Europe, two in Mexico and one each in China, Pakistan and the United States. Routine screening for secondary fungal infection was employed in 13 studies. The modified AspICU algorithm was utilised in 15 studies and was the most commonly used case definition and diagnostic algorithm for pulmonary aspergillosis. The incidence and mortality of CAPA in the ICU were estimated to be 10.2% (95% CI, 8.0-12.5; I = 82.0%) and 54.9% (95% CI, 45.6-64.2; I = 62.7%), respectively. In conclusion, our estimates may be utilised as a basis for surveillance of CAPA and prognostication in the ICU. Large, prospective cohort studies based on the new case definitions of CAPA are warranted to validate our estimates.
Topics: Adult; Aged; Aged, 80 and over; COVID-19; Cause of Death; Female; Humans; Incidence; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Middle Aged; SARS-CoV-2
PubMed: 33896063
DOI: 10.1111/myc.13292 -
The Journal of Hospital Infection Jul 2021COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. The purpose of this review was to...
COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. The purpose of this review was to discuss the incidence, characteristics, diagnostic criteria, biomarkers, and outcomes of hospitalized patients diagnosed with CAPA. A literature search was performed through Pubmed and Web of Science databases for articles published up to 20 March 2021. In 1421 COVID-19 patients, the overall CAPA incidence was 13.5% (range 2.5-35.0%). The majority required invasive mechanical ventilation (IMV). The time to CAPA diagnosis from illness onset varied between 8.0 and 16.0 days. However, the time to CAPA diagnosis from intensive care unit (ICU) admission and IMV initiation ranged between 4.0-15.0 days and 3.0-8.0 days. The most common diagnostic criteria were the modified AspICU-Dutch/Belgian Mycosis Study Group and IAPA-Verweij et al. A total of 77.6% of patients had positive lower respiratory tract cultures, other fungal biomarkers of bronchoalveolar lavage and serum galactomannan were positive in 45.3% and 18.2% of patients. The CAPA mortality rate was high at 48.4%, despite the widespread use of antifungals. Lengthy hospital and ICU stays ranging between 16.0-37.5 days and 10.5-37.0 days were observed. CAPA patients had prolonged IMV duration of 13.0-20.0 days. The true incidence of CAPA likely remains unknown as the diagnosis is limited by the lack of standardized diagnostic criteria that rely solely on microbiological data with direct or indirect detection of Aspergillus in respiratory specimens, particularly in clinical conditions with a low pretest probability. A well-designed, multi-centre study to determine the optimal diagnostic approach for CAPA is required.
Topics: Antifungal Agents; COVID-19; Humans; Incidence; Invasive Pulmonary Aspergillosis; Observational Studies as Topic; Respiration, Artificial
PubMed: 33891985
DOI: 10.1016/j.jhin.2021.04.012 -
Frontiers in Endocrinology 2021To analyze and summarize the clinical characteristics, treatments, and prognosis of Cushing's syndrome (CS) with nocardiosis.
OBJECTIVE
To analyze and summarize the clinical characteristics, treatments, and prognosis of Cushing's syndrome (CS) with nocardiosis.
METHODS
A patient in our hospital and additional 17 patients of CS with nocardiosis in the English literature were included in this study. Clinical characteristics, laboratory data, imaging studies, treatments, and prognosis were evaluated.
RESULTS
A 41-year-old man with CS was diagnosed and treated in our hospital. He had co-infections of nocardiosis and aspergillosis. Together with 17 patients of CS with nocardiosis in the English literature, 2 patients (11.1%) were diagnosed as Cushing's disease (CD) while 16 (88.9%) were diagnosed or suspected as ectopic ACTH syndrome (EAS). The average 24hrUFC was 7,587.1 ± 2,772.0 μg/d. The average serum total cortisol and ACTH (8 AM) was 80.2 ± 18.7 μg/dl and 441.8 ± 131.8 pg/ml, respectively. The most common pulmonary radiologic findings in CT scan were cavitary lesions (10/18) and nodules (8/18). Co-infections were found in 33.3% (6/18) patients. The CS patients with co-infections had higher levels of ACTH (671.5 ± 398.2 245.5 ± 217.1 pg/ml, = 0.047), and 38.9% (7/18) patients survived through the antibiotic therapy and the treatment of CS. Patients with lower level of ACTH (survival mortality: 213.1 ± 159.0 554.7 ± 401.0 pg/ml, P = 0.04), no co-infection, underwent CS surgery, and received antibiotic therapy for more than 6 months, had more possibilities to survive.
CONCLUSIONS
Nocardia infection should be cautioned when a patient of CS presented with abnormal chest radiographs. The mortality risk factors for CS with nocardiosis are high level of ACTH and co-infections. We should endeavor to make early etiological diagnosis, apply long-term sensitive antibiotics and aggressive treatments of CS.
Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Adult; Anti-Bacterial Agents; Cushing Syndrome; Female; Humans; Male; Middle Aged; Nocardia Infections; Prognosis; Radiography, Thoracic; Risk; Risk Factors
PubMed: 33854481
DOI: 10.3389/fendo.2021.640998 -
Journal of Fungi (Basel, Switzerland) Feb 2021The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases...
Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.
The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.
PubMed: 33670864
DOI: 10.3390/jof7030176 -
Mycoses Aug 2021Acute respiratory distress syndrome is a common complication of severe viral pneumonia, such as influenza and COVID-19, that requires critical care including ventilatory...
The double-edged sword of systemic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza-associated mucormycosis versus COVID-19 associated mucormycosis.
Acute respiratory distress syndrome is a common complication of severe viral pneumonia, such as influenza and COVID-19, that requires critical care including ventilatory support, use of corticosteroids and other adjunctive therapies to arrest the attendant massive airways inflammation. Although recommended for the treatment of viral pneumonia, steroid therapy appears to be a double-edged sword, predisposing patients to secondary bacterial and invasive fungal infections (IFIs) whereby impacting morbidity and mortality. Mucormycosis is a fungal emergency with a highly aggressive tendency for contiguous spread, associated with a poor prognosis if not promptly diagnosed and managed. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions including corticosteroid therapy are known risk factors for mucormycosis. Upon the background lung pathology, immune dysfunction and corticosteroid therapy, patients with severe viral pneumonia are likely to develop IFIs like aspergillosis and mucormycosis. Notably, the combination of steroid therapy and DM can augment immunosuppression and hyperglycaemia, increasing the risk of mucormycosis in a susceptible individual. Here, we report a case of sinonasal mucormycosis in a 44-year-old woman with hyperglycaemia secondary to poorly controlled diabetes following dexamethasone therapy on a background of influenza pneumonia and review 15 available literatures on reported cases of influenza and COVID-19 associated mucormycosis.
Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Antifungal Agents; COVID-19; Diabetes Complications; Female; Humans; Influenza, Human; Liposomes; Mucormycosis; Pneumonia, Viral; Triazoles
PubMed: 33590551
DOI: 10.1111/myc.13256 -
Mycopathologia May 2021Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19...
Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Diabetes Complications; Glucocorticoids; Humans; Kidney Failure, Chronic; Male; Middle Aged; Mucormycosis; Rhizopus; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33544266
DOI: 10.1007/s11046-021-00528-2 -
Neurospine Mar 2021Vertebral aspergillosis is quite rare conditions, often misdiagnosed, that requires long-term antibiotic therapy, and sometimes, surgical treatments. The present...
OBJECTIVE
Vertebral aspergillosis is quite rare conditions, often misdiagnosed, that requires long-term antibiotic therapy, and sometimes, surgical treatments. The present investigations were aimed to investigate the epidemiology, clinical-radiological aspects, treatment protocols, and outcomes of Aspergillus-mediated vertebral osteomyelitis.
METHODS
A systematic review of the pertinent English literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed. The research was conducted on Cochrane library, MEDLINE, PubMed, and Scopus using as search-terms "Aspergillus," "vertebral osteomyelitis," "spondylodiscitis," "spine infection." A case of vertebral aspergillosis conservatively managed was also reported.
RESULTS
Eighty-nine articles were included in our systematic review. Including the reported case, our analysis covered 112 cases of vertebral aspergillosis. Aspergillus fumigatus was isolated in 68 cases (61.2%), Aspergillus flavus in 14 (12.6%), Aspergillus terreus in 4 (3.6%), Aspergillus nidulans in 2 (1.8%). Seventy-three patients (65.7%) completely recovered at the last follow-up evaluation; in 7 patients (6.3%) radiological signs of chronic infection were reported, whereas 32 patients (28.8%) died during the follow-up.
CONCLUSION
This systematic review summarized the state of the art on vertebral aspergillosis, retrieving data on clinical features, diagnostic criteria and current limitations, treatment alternatives, and their outcomes.
PubMed: 33211946
DOI: 10.14245/ns.2040338.169 -
PloS One 2020Chronic pulmonary aspergillosis (CPA) requires prolonged treatment with itraconazole or voriconazole. However, adverse events (AEs) are common with the use of these... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Chronic pulmonary aspergillosis (CPA) requires prolonged treatment with itraconazole or voriconazole. However, adverse events (AEs) are common with the use of these agents, with the need to discontinue the offending drug in a significant proportion of the patients. The aim of this study was to evaluate the frequency of adverse events of itraconazole and voriconazole for the treatment of CPA.
METHODS
We searched Embase and Medline to select clinical studies providing information on AEs to itraconazole or voriconazole for the treatment of CPA from inception to May 2020. Reviews, single case reports, and case series reporting less than 10 patients were excluded. Random effect meta-analysis was performed using STATA 16.0.
RESULTS
We included 9 eligible studies with an overall total of 534 CPA patients enrolled. Of these, 69% (n = 366) were treated with voriconazole and 31% (n = 168) with itraconazole. The median daily dose of both itraconazole and voriconazole used was 400mg. In a pooled analysis, AEs were observed in 36% (95% CI: 20-52%, N = 366) of patients on voriconazole and 25% (95% CI: 18 to 31%, N = 168) in those treated with itraconazole. Discontinuation rate due to AEs was the same for both drugs; 35% (47/366) and 35% (15/168) for voriconazole and itraconazole, respectively. There were 70 AEs reported with itraconazole use, the commonest being cardiotoxicity (29%). Skin AEs (28%) were the most frequent among the 204 AEs reported with voriconazole use. None of the studies compared the tolerability of itraconazole head-to-head with voriconazole.
CONCLUSIONS
AEs due itraconazole and voriconazole are common and may lead to discontinuation of treatment in a significant proportion of patients. This information can be used to educate patients prior to commencement of these antifungal therapies.
PROSPERO REGISTRATION NUMBER
CRD42020191627.
Topics: Humans; Administration, Oral; Antifungal Agents; Cardiotoxicity; Itraconazole; Pulmonary Aspergillosis; Treatment Outcome; Voriconazole
PubMed: 33052954
DOI: 10.1371/journal.pone.0240374 -
Diagnostics (Basel, Switzerland) Oct 2020In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary... (Review)
Review
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.
PubMed: 33050499
DOI: 10.3390/diagnostics10100807