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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 -
The Cochrane Database of Systematic... 2004Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function.
OBJECTIVES
The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis.
SEARCH STRATEGY
We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003.
SELECTION CRITERIA
All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.
MAIN RESULTS
Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15).
REVIEWERS' CONCLUSIONS
Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Humans; Itraconazole; Ketoconazole; Randomized Controlled Trials as Topic
PubMed: 15266440
DOI: 10.1002/14651858.CD001108.pub2 -
Respirology (Carlton, Vic.) Nov 2016While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management... (Review)
Review
While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post-infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions (P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice.
Topics: Adult; Bronchiectasis; Diagnostic Techniques, Respiratory System; Disease Management; Humans; Observational Studies as Topic; Prevalence
PubMed: 27321896
DOI: 10.1111/resp.12832 -
Respiratory Medicine Oct 2004Allergic bronchopulmonary aspergillosis (ABPA) is a complex condition that affects people with asthma and cystic fibrosis (CF). It results from exposure to the fungus... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is a complex condition that affects people with asthma and cystic fibrosis (CF). It results from exposure to the fungus Aspergillus fumigatus, which leads to worsening airway inflammation and progressive damage to the lungs. The aim of this review is to outline the pathogenesis of the disorder, diagnostic criteria and to discuss the use of anti-fungal agents in its treatment.
METHODS
The Cochrane library of systematic reviews and the Cochrane database of controlled trials were searched for controlled trials on ABPA and its treatment in both asthma and CF. In addition, articles included within the reviews were examined separately, and a separate search carried out using Medline.
RESULTS
A systematic review for the use of azole anti-fungal agents in ABPA was identified for their use in both CF and non-CF-related disease. The review of ABPA alone identified two randomized-controlled trials of itraconazole in chronic disease. These trials demonstrated improvements in symptoms and immune activation, but were short-term trials and failed to show a significant change in lung function. No trials were identified in CF.
CONCLUSIONS
The use of anti-fungal agents in ABPA seems to be a rational one, with short-term efficacy demonstrated for the use of itraconazole. Further investigations are required to identify individuals who will benefit most from treatment and to establish the correct dose and means of delivering treatment in ABPA. Longer-term studies are required to demonstrate that treatment modifies the progressive decline in lung function seen with the disease.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Azoles; Evidence-Based Medicine; Forecasting; Humans; Itraconazole; Ketoconazole; Pyrimidines; Triazoles; Voriconazole
PubMed: 15481266
DOI: 10.1016/j.rmed.2004.07.002 -
International Journal of Infectious... Sep 2007Central nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the... (Review)
Review
OBJECTIVE
Central nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the pediatric population. We conducted this study to analyze characteristics of CNS aspergillosis in infants and children.
METHODS
The English literature was reviewed and all CNS aspergillosis cases in patients younger than 18 years of age were analyzed.
RESULTS
Ninety cases were recorded up to June 2005. The median age of the patients was 9 years, ranging from 18 days to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly presented as brain abscess(es), either single or multiple. While prematurity was the predominant underlying condition among infants, leukemia was the most frequent underlying disease in children. Aspergillus fumigatus was isolated from 75.5% of the cases. The overall mortality in published cases was 65.4%. In multivariate analysis, surgical treatment was independently associated with survival.
CONCLUSION
CNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients.
Topics: Adolescent; Aspergillus fumigatus; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Neuroaspergillosis
PubMed: 17509921
DOI: 10.1016/j.ijid.2007.01.013 -
American Journal of Transplantation :... Feb 2021To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies... (Meta-Analysis)
Meta-Analysis
To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.
Topics: Aspergillosis; Graft Rejection; Humans; Invasive Fungal Infections; Kidney Transplantation; Risk Factors
PubMed: 32780498
DOI: 10.1111/ajt.16248 -
The Cochrane Database of Systematic... Feb 2014Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.
OBJECTIVES
To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.
SEARCH METHODS
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.
SELECTION CRITERIA
Randomised clinical trials comparing voriconazole with amphotericin B or fluconazole.
DATA COLLECTION AND ANALYSIS
Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.
MAIN RESULTS
Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.
AUTHORS' CONCLUSIONS
Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole
PubMed: 24563222
DOI: 10.1002/14651858.CD004707.pub3 -
PloS One 2011Nucleic acid detection by polymerase chain reaction (PCR) is emerging as a sensitive and rapid diagnostic tool. PCR assays on serum have the potential to be a practical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nucleic acid detection by polymerase chain reaction (PCR) is emerging as a sensitive and rapid diagnostic tool. PCR assays on serum have the potential to be a practical diagnostic tool. However, PCR on bronchoalveolar lavage fluid (BALF) has not been well established. We performed a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays on BALF for invasive aspergillosis (IA).
METHODS
Relevant published studies were shortlisted to evaluate the quality of their methodologies. A bivariate regression approach was used to calculate pooled values of the method sensitivity, specificity, and positive and negative likelihood ratios. Hierarchical summary receiver operating characteristic curves were used to summarize overall performance. We calculated the post-test probability to evaluate clinical usefulness. Potential heterogeneity among studies was explored by subgroup analyses.
RESULTS
Seventeen studies comprising 1191 at-risk patients were selected. The summary estimates of the BALF-PCR assay for proven and probable IA were as follows: sensitivity, 0.91 (95% confidence interval (CI), 0.79-0.96); specificity, 0.92 (95% CI, 0.87-0.96); positive likelihood ratio, 11.90 (95% CI, 6.80-20.80); and negative likelihood ratio, 0.10 (95% CI, 0.04-0.24). Subgroup analyses showed that the performance of the PCR assay was influenced by PCR assay methodology, primer design and the methods of cell wall disruption and DNA extraction.
CONCLUSIONS
PCR assay on BALF is highly accurate for diagnosing IA in immunocompromised patients and is likely to be a useful diagnostic tool. However, further efforts towards devising a standard protocol are needed to enable formal validation of BALF-PCR.
Topics: Adult; Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; Humans; Polymerase Chain Reaction; Predictive Value of Tests; Probability; ROC Curve; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Software
PubMed: 22164295
DOI: 10.1371/journal.pone.0028467 -
Annals of Clinical Microbiology and... Jun 2021Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). (Review)
Review
BACKGROUND
Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).
METHODS
Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.
RESULTS
Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).
CONCLUSION
CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Topics: Antifungal Agents; Asia; Aspergillosis; Central Nervous System; Databases, Factual; Europe; Female; Humans; Leukemia; Male; Stem Cell Transplantation; Voriconazole
PubMed: 34130699
DOI: 10.1186/s12941-021-00452-9 -
Chronic Respiratory Disease 2008There are increasing reports describing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) without the classic risk... (Review)
Review
BACKGROUND
There are increasing reports describing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) without the classic risk factors for this severe infection. The available literature on this association is based on case reports or small case series. The aim of this review is to systematically review these cases and describe the clinical features, diagnostic studies and outcome.
METHODS
We identified all the cases of IPA and COPD reported in the literature and had enough clinical information. We also included five cases of IPA in patients with COPD identified by the authors. These cases were systematically reviewed for clinical features, diagnostic studies and outcome.
RESULTS
There were 60 cases of IPA in patients with COPD identified from the literature. The total number of cases reviewed was 65. The mean age was 65.1 years, the mean FEV1 was 39% of predicted (n = 17, range 19-56%). Forty-nine patients were documented to be on systemic corticosteroids. The mean dose was 24 mg/day (range 15-65 mg/day). Five patients were only on inhaled corticosteroids and in 11 patients there was no documentation of corticosteroid therapy. The clinical and radiological findings were nonspecific. Thirteen patients had documented evidence of disseminated IPA. Sputum examination was positive for Aspergillus in 76% and bronchoscopy with bronchoalveolar lavage that was positive in 70%. The diagnosis of IPA was definite in 43 patients and probable in 22 patients. Forty-six patients were treated with anti-fungal therapy. Fifty-nine patients (91%) died with IPA.
CONCLUSION
Invasive pulmonary aspergillosis is an emerging serious infection in patients with COPD. The majority of these patients have advanced COPD and/or on corticosteroid therapy. The clinical and radiological presentation is nonspecific. High index of suspicion is necessary for the timely treatment of these patients.
Topics: Aged; Aged, 80 and over; Amphotericin B; Aspergillosis; Comorbidity; Female; Humans; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Risk Factors
PubMed: 18303098
DOI: 10.1177/1479972307085637