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Lung Jun 2024Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case... (Review)
Review
BACKGROUND
Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.
METHODS
All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.
RESULTS
A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.
CONCLUSION
These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.
PubMed: 38898129
DOI: 10.1007/s00408-024-00717-y -
Clinical Microbiology and Infection :... May 2024Invasive fungal infections (IFIs) are common infectious complications after haematopoietic stem cell transplantation (HSCT), seriously threatening the survival of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infections (IFIs) are common infectious complications after haematopoietic stem cell transplantation (HSCT), seriously threatening the survival of patients.
OBJECTIVES
This systematic review aimed to investigate risk factors associated with IFIs following HSCT.
METHODS
Two authors independently conducted the selection of studies and extraction of data. Risk factors for IFIs, invasive aspergillosis or invasive mould infections and invasive candida infection after HSCT were compiled separately by meta-analysis using RevMan 5.4 and R language 4.1.2.
DATA SOURCES
Pubmed, EMBASE, Web of Science, and the Cochrane Library until April 2023.
STUDY ELIGIBILITY CRITERIA
Case-control or cohort studies that assessed risk factors for IFIs among HSCT recipients were included.
PARTICIPANTS
Patients experiencing HSCT.
TEST/S
None.
REFERENCE STANDARD
The IFIs were defined according to the European Organisation for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, or a similar definition.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale was used.
METHODS OF DATA SYNTHESIS
A random-effects model with the Mantel-Haenszel method was used to pool results from primary studies.
RESULTS
Out of 1637 studies screened, 51 studies involving 109 155 patients were included, with 45 studies providing adequate data for meta-analysis. Identified risk factors for IFIs included prolonged neutropenia, intensified therapy for graft-versus-host disease (GVHD), previous transplantation, previous proven or probable IFI, acute GVHD ≥ grade II, extensive or severe chronic GVHD, use of anti-thymocyte globulin during transplantation, haploidentical transplantation, high-dose glucocorticoids, Epstein-Barr virus infection, cytomegalovirus infection or reactivation, and lower albumin. Conversely, antifungal prophylaxis emerged as the sole preventive factor. For invasive aspergillosis or invasive mould infections, the top risk factors were extensive or severe chronic GVHD, respiratory viral infection, high-dose glucocorticoids, acute GVHD ≥ grade II, and human leukocyte antigen mismatch. Cord blood transplantation was the sole significant risk factor for invasive candidiasis. However, there was likely a high degree of interdependence among various risk factors.
DISCUSSION
This meta-analysis provides a thorough review of risk factors for IFIs infection after HSCT. The achieved insights can aid in stratifying patients who are at an elevated risk of IFIs and promoting antifungal preventive strategies.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Risk Factors; Graft vs Host Disease
PubMed: 38280518
DOI: 10.1016/j.cmi.2024.01.005 -
Journal de Mycologie Medicale Aug 2023Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved for various hematological malignancies. Invasive aspergillosis is a known complication of...
Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved for various hematological malignancies. Invasive aspergillosis is a known complication of ibrutinib, but mucormycosis is rare. We describe the case of a 70-year-old man with mantle cell lymphoma infiltrating the trachea, managed with a tracheobronchial stent and ibrutinib. He had improved one month after treatment, and we removed the airway stent. Four months later, he developed tracheal nodules confirmed to be tracheal mucormycosis and responded to liposomal amphotericin B (3.5 g) followed by posaconazole. After transient improvement, the tracheal lesions recurred, the biopsy showed lymphoma (with no evidence of mucormycosis), and he died. A systematic review of the literature identified 20 additional cases of ibrutinib-associated mucormycosis. Most of the 21 patients included were men (95%), and ibrutinib was the only risk factor in 15.7%. The reported mortality was 31.6% (6/19), attributable to mucormycosis in half the cases.
Topics: Male; Humans; Adult; Aged; Female; Mucormycosis; Trachea; Neoplasm Recurrence, Local; Piperidines
PubMed: 37523991
DOI: 10.1016/j.mycmed.2023.101414 -
Clinical Microbiology and Infection :... May 2024Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. (Review)
Review
BACKGROUND
Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics.
OBJECTIVES
To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis.
METHODS
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023.
STUDY ELIGIBILITY CRITERIA
Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis.
PARTICIPANTS
Adult and/or paediatric patients with CNS aspergillosis.
TEST(S)
Galactomannan testing on CSF specimens.
REFERENCE STANDARD
European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent.
ASSESSMENT OF RISK OF BIAS
QUADAS-2 assessment in duplicate.
METHODS OF DATA SYNTHESIS
Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none).
RESULTS
We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2-78.7%) and 94.4% (95% CI, 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies.
DISCUSSION
CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.
PubMed: 38810927
DOI: 10.1016/j.cmi.2024.05.013 -
Clinical Infectious Diseases : An... May 2024Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however,...
BACKGROUND
Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis.
METHODS
We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023.
RESULTS
We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%.
CONCLUSIONS
In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management.
PubMed: 38752732
DOI: 10.1093/cid/ciae203 -
Therapeutic Advances in Infectious... 2024The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported... (Review)
Review
BACKGROUND AND AIMS
The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported fungal infections ( spp., , or spp.) in adults after recovering from COVID-19.
METHODS
We performed a systematic review through PubMed, Web of Science, OVID-Medline, Embase, and Scopus. The study selection process was performed independently and by at least two authors. We performed a risk of bias assessment using the Newcastle-Ottawa Scale for cohort and case-control studies, and the Joanna Briggs Institute's Checklists for Case Series and Case Reports.
RESULTS
The systematic search found 33 studies meeting all inclusion criteria. There was a total population of 774 participants, ranging from 21 to 87 years. From them, 746 developed a fungal infection. In 19 studies, spp. was reported as the main mycosis. In 10 studies, was reported as the main mycosis. In seven studies, spp. was reported as the main mycosis. Regarding the quality assessment, 12 studies were classified as low risk of bias and the remaining studies as high risk of bias.
CONCLUSION
Patients' clinical presentation and prognosis after recovering from COVID-19 with fungal infection differ from those reported patients with acute COVID-19 infection and those without COVID-19 infection.
PubMed: 38706456
DOI: 10.1177/20499361241242963 -
Lung India : Official Organ of Indian... 2023The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating...
BACKGROUND
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma.
METHODS
We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression.
RESULTS
Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence.
CONCLUSIONS
There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.
PubMed: 37961961
DOI: 10.4103/lungindia.lungindia_69_23 -
Journal de Mycologie Medicale Nov 2023The therapeutic management of invasive aspergillosis should be guided by antifungal susceptibility testing (AFST). The disk diffusion (DD) method due to its simplicity... (Review)
Review
The therapeutic management of invasive aspergillosis should be guided by antifungal susceptibility testing (AFST). The disk diffusion (DD) method due to its simplicity and low cost could be an appropriate alternative to the reference methods (CLSI, EUCAST) which are not suitable for AFST in routine clinical microbiology laboratories, particularly in resource-constrained settings. This review summarizes the available data on the performance of the DD method in determining triazole susceptibility profile of Aspergillus species. The published articles on the performance of DD method for determining triazole susceptibility of Aspergillus spp. were systematically searched on major medical databases and Google Scholar. We identified 2725 articles of which 13 met the inclusion criteria. The overall average agreement value obtained between DD and CLSI broth microdilution (CLSI-BMD) methods for the itraconazole 10 µg disk (70.75%) was low especially when the medium used was not Mueller-Hinton (MH) agar. In contrast average agreement for the voriconazole 1 µg disk and the posaconazole 5 µg disk were > 94% regardless of media used. The correlation coefficient values between the DD and CLSI-BMD methods on MH agar were acceptable (≥ 0.71) for the itraconazole 10 µg disk and posaconazole 5 µg disk and good (≥ 0.80) for the voriconazole 1 and 10 µg disk. The reproducibility of the DD method regardless to the medium used was ≥ 82%. This systematic review shows that the disk diffusion method could be a real alternative for triazole antifungals susceptibility testing of Aspergillus spp.
Topics: Voriconazole; Itraconazole; Agar; Reproducibility of Results; Microbial Sensitivity Tests; Antifungal Agents; Triazoles; Aspergillus
PubMed: 37603962
DOI: 10.1016/j.mycmed.2023.101413 -
Transplantation Apr 2024Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant.
METHODS
We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant.
RESULTS
We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis.
CONCLUSIONS
Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.
Topics: Humans; Risk Factors; Organ Transplantation; Aspergillosis; Cytomegalovirus Infections; Invasive Fungal Infections; Candidiasis, Invasive; Transplant Recipients; Candidiasis
PubMed: 37953478
DOI: 10.1097/TP.0000000000004871 -
BMC Infectious Diseases Jan 2024With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common....
BACKGROUND/OBJECTIVE
With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals.
METHODS
A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review.
RESULT
The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%).
CONCLUSION
Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.
Topics: Humans; Coinfection; Retrospective Studies; Pulmonary Aspergillosis; Cryptococcosis; Aspergillosis
PubMed: 38229026
DOI: 10.1186/s12879-024-09014-8