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Clinical Microbiology and Infection :... Jul 2022Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies.
OBJECTIVES
We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.
DATA SOURCES
PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.
STUDY ELIGIBILITY CRITERIA
ICU cohort studies and CAPA case series including ≥3 patients were included.
PARTICIPANTS
Adult patients in ICUs with COVID-19.
INTERVENTIONS
Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.
METHODS
We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis.
RESULTS
Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival.
CONCLUSIONS
The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.
Topics: Adult; Antifungal Agents; COVID-19; Critical Care; Humans; Intensive Care Units; Pulmonary Aspergillosis
PubMed: 35150878
DOI: 10.1016/j.cmi.2022.01.027 -
The Journal of Allergy and Clinical... Mar 2023An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA.
METHODS
We conducted a systematic search across standard databases using specific key words until May 13, 2021. We performed a meta-analysis to compare the effectiveness (exacerbations, oral corticosteroid [OCS] use, lung function, and patient-reported asthma control) and safety of pre- and post-omalizumab treatment. Subgroup analyses were performed for treatment duration and underlying disease.
RESULTS
In total, 49 studies (n = 267) were included in the qualitative synthesis and 14 case series (n = 186) in the quantitative meta-analysis. Omalizumab treatment significantly reduced the annualized exacerbation rate compared with pretreatment (mean difference, -2.09 [95% CI, -3.07 to -1.11]; P < .01). There was a reduction in OCS use (risk difference, 0.65 [95% CI, 0.46-0.84]; P < .01), an increase in termination of OCS use (risk difference, 0.53 [95% CI, 0.24-0.82]; P < .01), and a reduction in OCS dose (milligrams per day) (mean difference, -14.62 [95% CI, -19.86 to -9.39]; P < .01) in ABPA patients receiving omalizumab. Omalizumab improved FEV % predicted by 11.9% (95% CI, 8.2-15.6; P < .01) and asthma control, and was well-tolerated.
CONCLUSIONS
Omalizumab treatment reduced exacerbations and OCS use, improved lung function and asthma control in patients with ABPA, and was well-tolerated. The results highlight the potential role of omalizumab in the treatment of ABPA.
Topics: Humans; Omalizumab; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Asthma; Adrenal Cortex Hormones
PubMed: 36581073
DOI: 10.1016/j.jaip.2022.12.012 -
JAMA Network Open Oct 2020Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Antifungal Prophylaxis Drugs in Patients With Hematological Disease or Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review and Network Meta-analysis.
IMPORTANCE
Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation (HSCT).
OBJECTIVE
To summarize the evidence on the efficacy and adverse effects of antifungal agents using an integrated comparison.
DATA SOURCES
Medline, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials were searched to collect all relevant evidence published in randomized clinical trials that assessed antifungal prophylaxis in patients with hematological disease. Sources were search from inception up to October 2019.
STUDY SELECTION
Studies that compared any antifungal agent with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or undergoing HSCT were included. Of 39 709 studies identified, 69 met the criteria for inclusion.
DATA EXTRACTION AND SYNTHESIS
The outcome from each study was estimated using the relative risk (RR) with 95% CIs. The Mantel-Haenszel random-effects model was used. The reliability and validity of the networks were estimated by addressing inconsistencies in the evidence from comparative studies of different treatments. Data were analyzed from December 2019 to February 2020. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-analysis (PRISMA-NMA) guideline.
MAIN OUTCOMES AND MEASURES
The primary outcomes were invasive fungal infections (IFIs) and mortality. The secondary outcomes were fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal owing to adverse effects of the drug.
RESULTS
We identified 69 randomized clinical trials that reported comparisons of 12 treatments with at total of 14 789 patients. Posaconazole was the treatment associated with the best probability of success against IFIs (surface under the cumulative ranking curve, 86.7%; mean rank, 2.5). Posaconazole treatment was associated with a significant reduction in IFIs (RR, 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis (RR, 0.36; 95% CI, 0.15-0.85) compared with placebo. Voriconazole was associated with a significant reduction in invasive candidiasis (RR, 0.15; 95% CI, 0.09-0.26) compared with placebo. However, posaconazole was associated with a higher incidence of withdrawal because of the adverse effects of the drug (surface under the cumulative ranking curve, 17.5%; mean rank, 9.2). In subgroup analyses considering efficacy and tolerance, voriconazole might be the best choice for patients undergoing HSCT, especially allogenic HSCT; however, posaconazole was ranked as the best choice for patients with acute myeloid leukemia or myelodysplastic syndrome.
CONCLUSIONS AND RELEVANCE
These findings suggest that voriconazole may be the best prophylaxis option for patients undergoing HSCT, and posaconazole may be the best prophylaxis option for patients with acute myeloid leukemia or myelodysplastic syndrome.
Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Female; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mycoses; Pre-Exposure Prophylaxis; Triazoles; Voriconazole
PubMed: 33030550
DOI: 10.1001/jamanetworkopen.2020.17652 -
Therapeutic Advances in Urology 2023Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes... (Review)
Review
BACKGROUND
Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes of patients with isolated renal and genito-urinary tract aspergillosis.
METHODS
We systematically searched Medline, CINAHL, Embase, African Journal Online, Google Scholar, and the Cochrane Library, covering the period from inception to August 2023 using the key terms 'renal' OR 'kidney*' OR 'prostate' OR 'urinary bladder' OR 'urinary tract*AND 'aspergillosis' OR 'aspergillus' OR 'aspergilloma' OR 'mycetoma'. We included single case reports or case series. Review articles, guidelines, meta-analyses, animal studies, protocols, and cases of genitourinary and /or renal aspergillosis occurring as a part of disseminated disease were excluded.
RESULTS
We identified 91 renal and urinary aspergillosis cases extracted from 76 publications spanning 1925-2023. Among the participants, 79 (86.8%) were male, with a median age of 46 years. Predominantly, presentations consisted of isolated renal infections (74 instances, 81.3%), followed by prostate (5 cases, 5.5%), and bladder (7 cases, 7.7%) involvement. (42.9%), (9.9%), and (1.1% each) were isolated. Underlying risk factors included diabetes mellitus (29.7%), HIV (12.1%), haematological malignancies (11%), and liver cirrhosis (8.8%), while common symptoms encompassed flank pain (36.3%), fever (33%), and lower urinary tract symptoms (20.9%). An autopsy was conducted in 8.8% of cases. Diagnostic work-up involved histopathology (70.5%), renal CT scans and urine microscopy and culture (52.6% each), and abdominal ultrasound (17.9%). Treatments included amphotericin B (34 cases, 37.4%) and azole-based regimens (29 cases, 31.9%). Nephrectomy was performed in 16 of 78 renal cases (20.5%). All-cause mortality was 24.4% (19 cases). No significant mortality rate difference was observed among antifungal regimens ( = 0.739) or nephrectomy status ( = 0.8).
CONCLUSION
Renal and urinary aspergillosis is an important cause of morbidity and mortality, particularly in immunocompromised and people with diabetes mellitus. While varied treatment strategies were observed, mortality rates showed no significant differences based on treatments or nephrectomy status. Further research is needed to refine diagnostics, optimize treatments, and enhance awareness among clinicians for early detection and management.
PROSPERO REGISTRATION NUMBER
CRD42023430959.
PubMed: 38130371
DOI: 10.1177/17562872231218621 -
Journal of the College of Physicians... May 2022Fungal infections have increased in number since the onset of this lethal pandemic. This study aimed to assess risk factors and case fatality in COVID-19 cases with...
Fungal infections have increased in number since the onset of this lethal pandemic. This study aimed to assess risk factors and case fatality in COVID-19 cases with aspergillosis or mucormycosis. A systematic review was done according to PRISMA guidelines. Databases used were Google scholar, Pakmedinet, PUBMED, and MEDLINE. Twenty-one case reports and case series of mucormycosis in COVID-19 patients were identified and the mean age was 56.3 years (36 men and 12 women). The most common comorbidity was diabetes and the site was rhino orbital mucormycosis. Case fatality of 48 combined cases was calculated to be 52%. Nineteen articles of aspergillosis were included. Diabetes was the most common comorbidity in cases. The number of affected men cases was more than women. The incidence of aspergillosis in critically sick COVID-19 patients was calculated to be 9.3%. Case fatality was calculated to be 51.2%. Screening can be a beneficial tool for decreasing morbidity and mortality. Key Words: COVID-19, Mucormycosis, Aspergillosis.
Topics: Aspergillosis; COVID-19; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Mucormycosis; SARS-CoV-2
PubMed: 35546702
DOI: 10.29271/jcpsp.2022.05.639 -
Surgical Infections Apr 2021Intestinal aspergillosis (IA) is a rare entity primarily discovered in immunocompromised patients. Because of its low incidence, IA is not considered routinely in the...
Intestinal aspergillosis (IA) is a rare entity primarily discovered in immunocompromised patients. Because of its low incidence, IA is not considered routinely in the differential of abdominal pain, distension, and diarrhea. A systematic characterization of demographics, comorbidities, clinical presentations, and outcomes can help surgeons recognize and manage IA in critically ill patients. Two independent authors carried out the literature search using PubMed, MEDLINE, and Scopus databases. The Mesh terms utilized were: 'intestinal' and 'aspergillosis' combined with the Boolean operator 'AND' (synonyms were combined with the Boolean operator 'OR'). Intestinal aspergillosis was defined as inflammation of the gastrointestinal tract (duodenum to rectum) caused by spp. All articles reporting IA were included. Articles describing aspergillosis of the esophagus or stomach were excluded. Statistical analysis was performed using SPSS software (version 18; SPSS Inc., Chicago, IL). Forty-two articles reporting 56 cases were included in the study. Mean age was 44.9 ± 20.5 years. Male to female ratio was 29:27. The most common condition in patients who developed IA was transplantation (19 patients; 34%). The most common clinical presentations of IA were abdominal pain (21 patients; 38%) and diarrhea 12 patients; 21%). Sixty-six percent of patients had primary IA whereas 34% developed IA secondarily to systemic infection. Diagnostic modalities included exploratory laparotomy (35 patients; 63%) and endoscopy (7 patients; 13%). Mean time to diagnosis was 8.6 ± 11.3 days. Intestinal aspergillosis was limited to the small bowel in 61% of patients. In 43 (77%) patients, bowel resection is the definitive treatment, whereas 13 (23%) patients underwent antifungal therapy alone. Mortality rate was 39%. Sixty-three percent of patients treated with surgery survived, compared with 46% treated with antifungal therapy alone (p = 0.34). Intestinal aspergillosis is a life-threatening condition with a mortality rate of 39%. Extrapulmonary IA is seen in patients with neutropenia, sepsis, inflammatory conditions, and immunosuppression. Patients who undergo surgery are more likely to survive this infection.
Topics: Adult; Aged; Antifungal Agents; Aspergillosis; Aspergillus; Chicago; Female; Humans; Immunocompromised Host; Male; Middle Aged; Young Adult
PubMed: 32758013
DOI: 10.1089/sur.2020.157 -
Mycoses Feb 2022Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of... (Review)
Review
Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of cirrhosis-associated immune dysfunction, humoral immunodeficiency, cell-mediated dysfunction and systemic inflammation. Besides classical risk factors for invasive fungal infection, acute-on-chronic liver failure, corticosteroid use, gastrointestinal bleeding, and prophylactic use of antibiotics are all additional conditions which are related to the potential development of fungal infections. Therefore, high-risk patients should be carefully followed by microbiological surveillance including cultures but also by imaging and fungal biomarkers for providing early diagnosis. Echinocandins are still the mainstay and first line antifungal therapy in cases of invasive candidiasis. Due to concerns of liver toxicity and in cases of renal impairment liposomal amphotericin B is a suitable alternative to voriconazole in patients with invasive pulmonary aspergillosis. Although, data of isavucoanzole and posaconazole use in those patients are also promising more specific studies in the subgroup of patients with liver impairment are needed. Especially, due to the late diagnosis and multiple organ dysfunction usually present in patients with liver impairment morbidity and mortality rates remain high. Based on the broad spectrum of diverse reports with varying content and quality and in some cases lack of evidence we performed a systematic review on this topic.
Topics: Antifungal Agents; Candidiasis, Invasive; Graft vs Host Disease; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Liver; Liver Diseases
PubMed: 34837414
DOI: 10.1111/myc.13403 -
European Journal of Clinical... Sep 2023A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff.
BACKGROUND
A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff.
METHODS
We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples.
RESULTS
Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789.
CONCLUSION
The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.
Topics: Humans; Sensitivity and Specificity; Bronchoalveolar Lavage Fluid; Pulmonary Aspergillosis; Bronchoalveolar Lavage; Mannans
PubMed: 37430166
DOI: 10.1007/s10096-023-04639-0 -
Risk factors for COVID-19-associated pulmonary aspergillosis: a systematic review and meta-analysis.The Lancet. Respiratory Medicine Mar 2024COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for CAPA have not been systematically addressed to date.
METHODS
In this systematic review and meta-analysis to identify factors associated with CAPA, we comprehensively searched five medical databases: Ovid MEDLINE; Ovid Embase; the Cochrane Database of Systematic Reviews; the Cochrane Central Register of Controlled Trials; and the WHO COVID-19 Database. All case-control and cohort studies in adults (aged >18 years) that described at least six cases of CAPA and evaluated any risk factors for CAPA, published from Dec 1, 2019, to July 27, 2023, were screened and assessed for inclusion. Only studies with a control population of COVID-19-positive individuals without aspergillosis were included. Two reviewers independently screened search results and extracted outcome data as summary estimates from eligible studies. The primary outcome was to identify the factors associated with CAPA. Meta-analysis was done with random-effects models, with use of the Mantel-Haenszel method to assess dichotomous outcomes as potential risk factors, or the inverse variance method to assess continuous variables for potential association with CAPA. Publication bias was assessed with funnel plots for factors associated with CAPA. The study is registered with PROSPERO, CRD42022334405.
FINDINGS
Of 3561 records identified, 27 articles were included in the meta-analysis. 6848 patients with COVID-19 were included, of whom 1324 (19·3%) were diagnosed with CAPA. Diagnosis rates of CAPA ranged from 2·5% (14 of 566 patients) to 47·2% (58 of 123). We identified eight risk factors for CAPA. These factors included pre-existing comorbidities of chronic liver disease (odds ratio [OR] 2·70 [95% CI 1·21-6·04], p=0·02; I=53%), haematological malignancies (OR 2·47 [1·27-4·83], p=0·008; I=50%), chronic obstructive pulmonary disease (OR 2·00 [1·42-2·83], p<0·0001; I=26%), and cerebrovascular disease (OR 1·31 [1·01-1·71], p=0·05; I=46%). Use of invasive mechanical ventilation (OR 2·83; 95% CI 1·88-4·24; p<0·0001; I=69%), use of renal replacement therapy (OR 2·26 [1·76-2·90], p<0·0001; I=14%), treatment of COVID-19 with interleukin-6 inhibitors (OR 2·88 [1·52-5·43], p=0·001; I=89%), and treatment of COVID-19 with corticosteroids (OR 1·88 [1·28-2·77], p=0·001; I=66%) were also associated with CAPA. Patients with CAPA were typically older than those without CAPA (mean age 66·6 years [SD 3·6] vs 63·5 years [5·3]; mean difference 2·90 [1·48-4·33], p<0·0001; I=86%). The duration of mechanical ventilation in patients with CAPA was longer than in those without CAPA (n=7 studies; mean duration 19·3 days [8·9] vs 13·5 days [6·8]; mean difference 5·53 days [1·30-9·77], p=0·01; I=88%). In post-hoc analysis, patients with CAPA had higher all-cause mortality than those without CAPA (n=20 studies; OR 2·65 [2·04-3·45], p<0·0001; I=51%).
INTERPRETATION
The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19.
FUNDING
None.
Topics: Adult; Humans; Aged; COVID-19; Pulmonary Aspergillosis; Aspergillosis; Continuous Renal Replacement Therapy; Databases, Factual
PubMed: 38185135
DOI: 10.1016/S2213-2600(23)00408-3 -
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