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Medical Mycology Jun 2024Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In...
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.
Topics: Humans; Aspergillus fumigatus; Antifungal Agents; Aspergillosis; World Health Organization; Drug Resistance, Fungal; Voriconazole; Incidence; Microbial Sensitivity Tests; Invasive Fungal Infections; Risk Factors
PubMed: 38935907
DOI: 10.1093/mmy/myad129 -
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 -
Therapeutic Advances in Infectious... 2024, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called... (Review)
Review
BACKGROUND
, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of , and risk factors, mortality rate, and underlying condition associated with aspergillosis.
METHODS
Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis.
RESULTS
was prominently reported ( = 2679, 75.14%), followed by ( = 437, 12.25%), ( = 219, 6.14%), and ( = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases ( = 1956) and possible cases ( = 341). In patients, cough emerged as the most common complaint ( = 1819, 18.54%), followed by asthma ( = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing ( = 12, 25.53%), Guangdong ( = 7, 14.89%), and Shanghai ( = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency ( = 8, 7.92%), Guangdong recorded a relatively high number ( = 3, 37.5%), followed by Beijing ( = 2, 25.0%), and Shanghai ( = 1, 12.5%). Percentage of death reported: IPA had the highest rate ( = 447, 68.87%), followed by CPA ( = 181, 27.88%) and ABPA ( = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease ( = 3765, 60.53%), previous tuberculosis ( = 416, 6.68%), and organ transplant or organ failure ( = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy ( = 622, 10.0%).
CONCLUSION
This review sheds light on the prevalence patterns of species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies.
REGISTRATION
This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.
PubMed: 38835831
DOI: 10.1177/20499361241252537 -
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 -
BMC Infectious Diseases Mar 2024Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients' demographics, clinical manifestations,...
BACKGROUND
Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients' demographics, clinical manifestations, diagnosis, management, and outcome.
METHODS
We performed a systematic review of the literature using MEDLINE and LILACS databases. We searched for articles published in the period from January 1990 to December 24, 2022, to identify patients who developed liver abscesses due to Aspergillus spp.
RESULTS
Our search yielded 21 patients all of whom had invasive aspergillosis confirmed on liver biopsy. Of these patients 81% were adults, and 60% were males. The majority (86%) of patients were immunocompromised and 95% had symptomatic disease at the time of diagnosis. The most common symptoms were fever (79%), abdominal pain (47%), and constitutional symptoms (weight loss, chills, night sweats, fatigue) (38%). Liver enzymes were elevated in 50%, serum galactomannan was positive in 57%, and fungal blood cultures were positive in only 11%. Co-infection with other pathogens preceded development of apsergillosis in one-third of patients, and the majority of the abscesses (43%) were cryptogenic. In the remaining patients with known source, 28% of patients developed liver abscess through dissemination from the lungs, 19% through the portal vein system, and in 10% liver abscess developed through contiguous spread. The most common imaging modality was abdominal computerized tomography done in 86% of patients. Solitary abscess was present in 52% of patients while 48% had multiple abscesses. Inadequate initial empiric therapy was prescribed in 60% of patients and in 44% of patients definite treatment included combination therapy with two or more antifungal agents. Percutaneous drainage of the abscesses was done in 40% of patients, while 20% required liver resection for the treatment of the abscess. Overall mortality was very high at 38%.
CONCLUSION
Further studies are urgently needed for a better understanding of pathophysiology of liver aspergillosis and for developement of newer blood markers in order to expedite diagnosis and decrease mortality.
Topics: Male; Adult; Humans; Female; Liver Abscess; Aspergillus; Aspergillosis; Combined Modality Therapy
PubMed: 38519916
DOI: 10.1186/s12879-024-09226-y -
BMC Infectious Diseases Feb 2024Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies.
METHODS
We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity.
RESULTS
A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I = 26.1%) than those without the disease (p < 0.0001). No significant moderators could explain the observed heterogeneity in age difference. However, subgroup analysis revealed that age differences were more pronounced within particular patient groups compared to others. For example, patients with and without IA who had primary severe lung infections exhibited a greater difference in mean age than other patient cohorts.
CONCLUSIONS
Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes.
Topics: Humans; Retrospective Studies; Aspergillosis; Invasive Fungal Infections; Databases, Factual; Probability
PubMed: 38373908
DOI: 10.1186/s12879-024-09109-2 -
Open Forum Infectious Diseases Jan 2024Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes. (Review)
Review
BACKGROUND
Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes.
METHODS
A systematic literature search using the Ovid MEDLINE and EMBASE databases identified manuscripts describing human mucormycosis diagnosed according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group criteria with therapeutic outcomes published from 2000 to 2022.
RESULTS
In 126 articles, 10 335 patients were described, most from Asia (n = 6632, 66%). Diabetes was the most frequent underlying disease (n = 6188, 60%); 222 (2.1%) patients had no underlying diseases. The dominant clinical form was rhino-orbitocerebral (n = 7159, 69.3%), followed by pulmonary (n = 1062, 10.3%). Of 5364 patients with outcome data, amphotericin B monotherapy (n = 3749, mortality 31.5%) was most frequent, followed by amphotericin B + azole (n = 843, mortality 6.6%; < .0001), amphotericin B followed by azole (n = 357, mortality 13.7%; < .0001), posaconazole only (n = 250, mortality 17.2%; < .0001), and isavuconazole only (n = 65, mortality 24.6%; = .24). Duration and dose of antifungals varied widely. Documented outcomes from surgical resections in 149 patients found that 47 of 125 died (37.6%), compared with 16 of 24 (66.7%) patients who did not undergo surgery ( = .008).
CONCLUSIONS
Mucormycosis is more frequently reported in Asia than in Europe and is often linked to diabetes. Antifungal therapy, usually with surgery, is frequently effective for mucormycosis.
PubMed: 38288347
DOI: 10.1093/ofid/ofad704 -
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