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The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Health Science Reports Sep 2022COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19...
COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19 associated mucormycosis (CAM) and aspergillosis (CAA), have recently been highly acquainted by many worldwide cases. Two immune response deteriorating factors are considered to be responsible for immunosuppression: comorbidities and medication. Due to unlike infection sites and patterns, CAM and CAA-associated factors deflect a few degrees of proximity, and the present study is for its assessment. The study evaluated 351 CAM cases and 191 CAA cases retrieved from 65 and 53 articles based on inclusion criteria, respectively. Most of the CAM reported from India and CAA were from four South-European and West-European neighbor countries. The mean ages of CAM and CAA were 52.72 ± 13.74 and 64.81 ± 11.14, correspondingly. Mortality of CAA (56.28%) was two times greater than CAM (26.02%). Nevertheless, the count of diabetes cases was very high in CAM compared to CAA. The main comorbidities of CAM were diabetes (nearly 80%) and hypertension (more than 38%). All noticeable complications were higher in CAA except diabetes, and these were diabetes (34.55%), hypertension (45.03%), and obesity (18.32%). Moreover, pre-existing respiratory complications like asthma and chronic obstructive pulmonary disease are visible in CAA. The uses of steroids in CAM and CAA were nearly 70% and 66%, respectively. Almost one-fourth of CAA cases were reported using immunosuppressant monoclonal antibodies, whereas only 7.69% were for CAM. The overall finding highlights diabetes, hypertension, and steroids as the risk factors for CAM, whereas obesity, chronic pulmonary disease, and immunosuppressants for CAA.
PubMed: 36000078
DOI: 10.1002/hsr2.789 -
Mycoses Jan 2023Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and... (Review)
Review
BACKGROUND
Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature.
CASE DESCRIPTION AND SYSTEMATIC REVIEW
A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26; 19.2%) or bronchoscopic instillation (1/26; 3.8%) of amphotericin B and surgery (6/26; 23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis.
CONCLUSION
Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible.
Topics: Male; Humans; Middle Aged; Female; Mucormycosis; Amphotericin B; Antifungal Agents; Hemoptysis; COVID-19
PubMed: 35984683
DOI: 10.1111/myc.13519 -
Clinical Imaging Oct 2022Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This...
PURPOSE
Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA).
METHODS
A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities.
RESULTS
The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%).
CONCLUSION
CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.
Topics: Aged; COVID-19; Data Analysis; Humans; Lung; Male; Middle Aged; Pulmonary Aspergillosis; Tomography, X-Ray Computed
PubMed: 35908455
DOI: 10.1016/j.clinimag.2022.07.003 -
Medical Mycology Aug 2022Emergence of triazole resistance has been observed in Aspergillus fumigatus over the past decade including Africa. This review summarizes the current published data on...
UNLABELLED
Emergence of triazole resistance has been observed in Aspergillus fumigatus over the past decade including Africa. This review summarizes the current published data on the epidemiology and reported mechanisms of triazole-resistant Aspergillus fumigatus (TRAF) in both environmental and clinical isolates from Africa. Searches on databases Medline, PubMed, HINARI, Science Direct, Scopus and Google Scholar on triazole resistance published between 2000 and 2021 from Africa were performed. Isolate source, antifungal susceptibility using internationally recognized methods, cyp51A mechanism of resistance and genotype were collected. Eleven published African studies were found that fitted the search criteria; these were subsequently analyzed. In total this constituted of 1686 environmental and 46 clinical samples. A TRAF prevalence of 17.1% (66/387) and 1.3% (5/387) was found in respectively environmental and clinical settings in African studies. Resistant to itraconazole, voriconazole, and posaconazole was documented. Most of the triazole-resistant isolates (30/71, 42.25%) were found to possess the TR34/L98H mutation in the cyp51A-gene; fewer with TR46/Y121F/T289A (n = 8), F46Y/M172V/E427K (n = 1), G54E (n = 13), and M172V (n = 1) mutations. African isolates with the TR34/L98H, TR46/Y121F/T289A and the G54E mutations were closely related and could be grouped in one of two clusters (cluster-B), whereas the cyp51A-M172V mutation clustered with most cyp51A-WT strains (cluster-A). A single case from Kenya shows that TR34/L98H from environmental and clinical isolates are closely related. Our findings highlight that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries. There is need for epidemiological surveillance to determine the true burden of the problem in Africa.
LAY SUMMARY
Emergence of triazole resistance has been observed in Aspergillus fumigatus. TRAF was found from environmental (17.1%) and clinical (1.3%) settings in Africa. We highlighted that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries.
Topics: Animals; Antifungal Agents; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Fungal Proteins; Microbial Sensitivity Tests; Triazoles
PubMed: 35906879
DOI: 10.1093/mmy/myac059 -
European Respiratory Review : An... Sep 2022is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for... (Review)
Review
BACKGROUND
is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF.
OBJECTIVE
To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF.
METHODS
A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932).
RESULTS
A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA.
CONCLUSION
Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.
Topics: Adult; Child; Humans; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Biological Products; Cystic Fibrosis
PubMed: 35896271
DOI: 10.1183/16000617.0011-2022 -
Journal of Fungi (Basel, Switzerland) Jul 2022Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies... (Review)
Review
Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies (HMs). At the highest risk of mortality are those with disseminated disease to the central nervous system, known as cerebral aspergillosis (CA). However, little is known about the risk factors contributing to disease amongst HM patients. A systematic review using PRISMA guidelines was undertaken to define HM patient subgroups, preventative measures, therapeutic interventions, and outcomes of patients with disseminated CA following IPA. The review resulted in the identification of 761 records, of which 596 articles were screened, with the final inclusion of 47 studies and 76 total patients. From included articles, the proportion of CA was assessed amongst HM patient subgroups. Further, pre-and post-infection characteristics, fungal species, and mortality were evaluated for the total population included and HM patient subgroups. Patients with acute myeloid leukemia and acute lymphoid lymphoma, patients receiving corticosteroids as a part of their HM therapeutic regimen, and anti-fungal prophylaxis constitute the top identified patient populations at risk for disseminated CA. Overall, information presented here indicates that measures for the prevention of IPA should be taken in higher-risk HM patient subgroups. Specifically, the type of anti-fungal therapy used should be carefully considered for those patients with IPA and increased risk for cerebral dissemination. Additional reports detailing patient characteristics are needed to define further the risk of developing disseminated CA from IPA in patients with HMs.
PubMed: 35887477
DOI: 10.3390/jof8070722 -
Medical Mycology Aug 2022Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is...
UNLABELLED
Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is to investigate the current literature regarding Aspergillus spp. osteoarticular infections. An electronic search of the PubMed and Scopus databases was conducted considering studies that assessed osteoarticular infections from Aspergillus spp. We included only studies with biopsy proven documentation of positive cultures or histological findings for Aspergillus spp., and those with essential information for each case such as the anatomical location of the infection, the type of treatment (conservative, surgical, combination), the antifungal therapy, and the outcome. Overall, 148 studies from 1965 to 2021 including 186 patients were included in the review. One hundred and seven (57.5%) patients underwent surgical debridement in addition to antifungal therapy, while 79 (42.7%) patients were treated only conservatively. Complete infection resolution was reported in 107 (57.5%) patients, while partial resolution in 29 (15.5%) patients. Surgical debridement resulted in higher complete infection resolution rate compared to only antifungal therapy (70.0% vs. 40.5%, P < 0.001), while complete resolution rate was similar for antifungal monotherapy and combination/sequential therapy (58.3% vs. 54.5%; P = 0.76). Last, complete resolution rate was also similar for monotherapy with amphotericin B (58.1%) and voriconazole (58.6%; P = 0.95). The results of this study indicate that antifungal monotherapy has similar efficacy with combination/sequential therapy, while voriconazole has similar efficacy with amphotericin B. Moreover, surgical debridement of the infected focus results in better outcomes in terms of infection eradication compared to conservative treatment.
LAY SUMMARY
Antifungal monotherapy has similar efficacy with combination/sequential therapy, and voriconazole has similar efficacy with amphotericin B for the treatment of Aspergillus spp. osteoarticular infections, while surgical debridement of the infected focus improves the infection eradication rate.
Topics: Animals; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Microbial Sensitivity Tests; Treatment Outcome; Voriconazole
PubMed: 35867975
DOI: 10.1093/mmy/myac052 -
PloS One 2022This systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.
OBJECTIVES
This systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.
METHODS
PubMed, Web of Science, Scopus, Cochrane Library, SID, Magiran, IranDoc, and Google Scholar were searched for Persian and English articles published from January 1, 2020, to November 5, 2021, using a systematic search strategy. Studies on Iranian patients suffering from CAFIs were included in the review.
RESULTS
Twenty-two studies comprising 169 patients were retrieved. Reported CAFIs included candidiasis (85, 50.30%), mucormycosis (35, 20.71%), aspergillosis (29, 17.16%), fusariosis (6, 3.55%), three cases caused by rare pathogens (Rhodotorula mucilaginosa, Diaporthe foeniculina, and Sarocladium kiliense) and 11 (6.51%) uncharacterized mold infections. The most common underlying diseases were diabetes (67/168, 39.88%), cardiovascular diseases (55/168, 32.74%), and hypertension (43/168, 25.59%). The use of antibiotics (111/124, 89.52%), corticosteroids (93/132, 70.44%), and mechanical ventilation (66, 51.16%) were the most common predisposing factors. Totally, 72 (50.35%) of 143 patients with CAFIs died (data were not available for 26 patients).
CONCLUSION
Fungal infections are evident to be a complication of COVID-19 in Iran; thus, clinicians should consider them as a differential diagnosis, especially in patients with comorbidities and previous antibiotic or corticosteroid use.
Topics: COVID-19; Diabetes Mellitus; Humans; Iran
PubMed: 35816494
DOI: 10.1371/journal.pone.0271333 -
Mycoses Sep 2022The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary... (Meta-Analysis)
Meta-Analysis
Comparative diagnostic accuracy of immunoprecipitation versus immunoassay methods for detecting Aspergillus fumigatus-specific IgG in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis.
BACKGROUND
The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary aspergillosis (ABPA) complicating asthma remains unclear.
METHODS
We performed a systematic review to identify studies describing both the methods in the same ABPA subjects. We assessed study quality using the QUADAS-2 tool. We derived the relative sensitivity and specificity using the HSROC meta-regression model. We calculated the number-needed-to-test using an immunoassay to detect one additional positive test in ABPA.
RESULTS
Our search yielded 20 studies (796 ABPA and 929 controls). The studies had a high risk of bias. The summary estimates for sensitivity and specificity of immunoprecipitation methods were 68.6% (95% CI, 48.4-83.5) and 93.8% (95% CI, 83.6-97.8), respectively, while for immunoassays they were 85.2% (95% CI, 73.3-92.3) and 84.6% (95% CI, 76.0-90.5), respectively. The relative sensitivity and specificity of immunoassays compared to immunoprecipitation tests were 1.29 (95% CI, 1.1-1.6) and 0.91 (95% CI, 0.85-0.97), respectively. The automated immunoassays (1.77; 95% CI, 1.1-2.8) had better relative sensitivity than the manual (1.1; 95% CI, 1.02-1.18) assays compared to immunoprecipitation. The relative specificity of manual immunoassays (0.95; 95% CI, 0.91-0.99) was significantly lower, while that of automated (0.88; 95% CI, 0.77-1.0) assays was lower but not statistically different. One additional positive result was detected for every six (95% CI, 5-7) tests performed with immunoassay (versus immunoprecipitation).
CONCLUSION
Compared to immunoprecipiation methods, automated immunoassays have higher sensitivity and similar specificity, manual immunoassays have higher sensitivity and lower specificity, while automated immunoassays have higher sensitivity and similar specificity for detecting A.fumigatus-IgG in patients with ABPA. [www.crd.york.ac.uk/prospero/display_record.php?RecordID=309864].
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Humans; Immunoassay; Immunoglobulin G; Immunoprecipitation
PubMed: 35757847
DOI: 10.1111/myc.13488