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American Journal of Transplantation :... Apr 2022Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the... (Meta-Analysis)
Meta-Analysis
Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the highest mortality rate. However, risk factors associated with IFIs have only been evaluated in small single-center studies. We performed a meta-analysis by conducting a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of controlled trials. All case-control and cohort studies evaluating risk factors for IFIs in adult LTRs were screened. Utilizing a random-effects model, a multivariate analysis was completed, and 28 studies were eligible for meta-analysis. Rates of IFIs ranged from 1.4% to 32.7%. Previous antibiotic use (OR 9.3; 95% CI 3.2-27.0) and bacterial infection (OR 4.3; 95% CI 2.1-8.6) were risk factors of invasive candidiasis. Yet for invasive aspergillosis, posttransplant renal replacement therapy (OR 9.2; 95% CI 4.2-20.4), reoperation (OR 8.0; 95% CI 2.9-21.7), and cytomegalovirus infection (OR 6.2; 95% CI 2.0-19.3) were risk factors. The top independent risk factors for IFIs during studies from 2010 to 2019 were previous fungal colonization (OR 9.19; 95% CI 4.92-17.16), reoperation (OR 5.45; 95% CI 2.93-10.15), and previous bacterial infections (OR 3.81; 95% CI 2.13-6.83). These risk factors may be targeted by antifungal prophylaxis in LTRs.
Topics: Adult; Antifungal Agents; Candidiasis; Humans; Invasive Fungal Infections; Liver Transplantation; Risk Factors; Transplant Recipients
PubMed: 34953174
DOI: 10.1111/ajt.16935 -
Immunity, Inflammation and Disease Jan 2023Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta-analysis.
OBJECTIVE
This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta-analysis.
METHODS
We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses.
RESULTS
In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001).
CONCLUSIONS
Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluid Aspergillus antigen testing, culture, and biopsy.
Topics: Humans; Superinfection; Sensitivity and Specificity; Aspergillus; Invasive Pulmonary Aspergillosis; Risk Factors; Neoplasms
PubMed: 36705416
DOI: 10.1002/iid3.760 -
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 -
Advances in Therapy Dec 2019Fungi are responsible for around 20% of microbiologically documented infections in intensive care units (ICU). In the last decade, the incidence of invasive fungal...
Fungi are responsible for around 20% of microbiologically documented infections in intensive care units (ICU). In the last decade, the incidence of invasive fungal infections (IFI), including candidemia, has increased steadily because of increased numbers of both immunocompromised and ICU patients. To improve the outcomes of patients with IFI, intensivists need to be aware of the inherent challenges. This narrative review summarizes the features of routinely used treatments directed against IFI in non-neutropenic ICU patients, which include three classes of antifungals: polyenes, azoles, and echinocandins. ICU patients' pathophysiological changes are responsible for deep changes in the pharmacokinetics of antifungals. Moreover, drug interactions affect the response to antifungal treatments. Consequently, appropriate antifungal dosage is a challenge under these special conditions. Dosages should be based on renal and liver function, and serum concentrations should be monitored. This review summarizes recent guidelines, focusing on bedside management.
Topics: Antifungal Agents; Azoles; Drug Interactions; Drug Monitoring; Echinocandins; Humans; Immunocompromised Host; Incidence; Intensive Care Units; Invasive Fungal Infections; Kidney Function Tests; Liver Function Tests; Polyenes; Practice Guidelines as Topic
PubMed: 31617055
DOI: 10.1007/s12325-019-01115-0 -
Scientific Reports Sep 2020Invasive fungal infections are a potentially life-threatening complication in immunocompromised patients. The aim of this study was to assess the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: a systematic review with meta-analysis and trial sequential analysis.
Invasive fungal infections are a potentially life-threatening complication in immunocompromised patients. The aim of this study was to assess the efficacy and safety of posaconazole as compared with other antifungal agents for preventing invasive fungal infections in immunocompromised patients. Embase, CENTRAL, and MEDLINE were searched for randomized conweekmonthtrolled trials (RCTs) up to June 2020. A systematic review with meta-analysis of RCTs was performed using random-effects model. Trial sequential analysis (TSA) was conducted for the primary outcome to assess random errors. A total of five RCTs with 1,617 participants were included. Posaconazole prophylaxis was associated with a significantly lower risk of IFIs (RR, 0.43 [95% CI 0.28 to 0.66, p = 0.0001]) as compared to other antifungal agents. No heterogeneity was identified between studies (I = 0%). No significant associations were observed for the secondary outcomes measured, including risk reduction of invasive aspergillosis and candidiasis, clinical failure, all-cause mortality, and treatment-related adverse events, except for infection-related mortality (RR, 0.31 [95% CI 0.15 to 0.64, p = 0.0001]). Subgroup analysis favoured posaconazole over fluconazole for the prevention of IFIs (RR, 0.44 [95% CI 0.28 to 0.70, p = 0.0004]). TSA confirmed the prophylactic benefit of posaconazole against IFIs. Posaconazole is effective in preventing IFIs among immunocompromised patients, particularly those with hematologic malignancies and recipients of allogenic hematopoietic stem cell transplantation.
Topics: Antifungal Agents; Candidiasis; Fluconazole; Humans; Immunocompromised Host; Invasive Fungal Infections; Mycoses; Randomized Controlled Trials as Topic
PubMed: 32884060
DOI: 10.1038/s41598-020-71571-0 -
Lung India : Official Organ of Indian... 2018Allergic bronchopulmonary aspergillosis (ABPA) is a complex inflammatory lung disorder complicating bronchial asthma and cystic fibrosis. Although the condition responds...
Allergic bronchopulmonary aspergillosis (ABPA) is a complex inflammatory lung disorder complicating bronchial asthma and cystic fibrosis. Although the condition responds to treatment with glucocorticoids and antifungal drugs, lack of timely recognition, and inadequate treatment of ABPA can lead to progressive lung damage. Uncommonly, long standing inflammation and bronchiectasis can also lead to the development of secondary amyloidosis. Herein, we report a case of ABPA, which presented as nephrotic syndrome and progressed rapidly to end-stage renal disease.
PubMed: 29970774
DOI: 10.4103/lungindia.lungindia_180_17 -
Antimicrobial Agents and Chemotherapy Aug 2018Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize...
Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments. We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). We searched Embase, PubMed, the Cochrane Central Register of Controlled Clinical Trials, and the www.ClinicalTrials.gov website. In total, 54 RCTs were identified, including 13 treatment options. The evidence was synthesized using a network meta-analysis. Relative risk (RR) was adopted. Posaconazole was ranked highest in effectiveness for primary prophylaxis, being the most favorable in terms of (i) the RR for reduction of invasive fungal infection (0.19; 95% confidence interval [CI], 0.11 to 0.36) and (ii) the probability of being the best option (94% of the cumulative ranking). Posaconazole also demonstrated its efficacy in preventing invasive aspergillosis and proven fungal infections, with RR of 0.13 (CI, 0.03 to 0.65) and 0.14 (CI, 0.05 to 0.38), respectively. However, there was no significant difference among all of the antifungal agents in all-cause mortality and overall adverse events. Our network meta-analysis provided an integrated overview of the relative efficacy of all available treatment options for primary fungal prophylaxis for neutropenic fever in hematological malignancy patients under myelosuppressive chemotherapy or hematopoietic cell transplantation. On the basis of this analysis, posaconazole seems to be the most effective prophylaxis option until additional data from head-to-head randomized controlled trials become available.
Topics: Antifungal Agents; Aspergillosis; Fever; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Invasive Fungal Infections; Network Meta-Analysis; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic; Triazoles
PubMed: 29866872
DOI: 10.1128/AAC.00355-18 -
The Cochrane Database of Systematic... Oct 2015Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are increasingly being investigated.
OBJECTIVES
To provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people.
SEARCH METHODS
We searched MEDLINE (1946 to June 2015) and EMBASE (1980 to June 2015). We also searched LILACS, DARE, Health Technology Assessment, Web of Science and Scopus to June 2015. We checked the reference lists of all the studies identified by the above methods and contacted relevant authors and researchers in the field.
SELECTION CRITERIA
We included studies that: i) compared the results of blood PCR tests with the reference standard published by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false-negative and true-negative results of the diagnostic tests under investigation separately; and iii) evaluated the test(s) prospectively in cohorts of people from a relevant clinical population, defined as a group of individuals at high risk for invasive aspergillosis. Case-control studies were excluded from the analysis.
DATA COLLECTION AND ANALYSIS
Authors independently assessed quality and extracted data. For PCR assays, we evaluated the requirement for either one or two consecutive samples to be positive for diagnostic accuracy. We investigated heterogeneity by subgroup analyses. We plotted estimates of sensitivity and specificity from each study in receiver operating characteristics (ROC) space and constructed forest plots for visual examination of variation in test accuracy. We performed meta-analyses using the bivariate model to produce summary estimates of sensitivity and specificity.
MAIN RESULTS
Eighteen primary studies, corresponding to 19 cohorts and 22 data sets, published between 2000 and 2013 were included in the meta-analyses, with a median prevalence of IA (proven or probable) of 12.0% (range 2.5 to 30.8 %). The majority of people had received chemotherapy for a haematological malignancy or had undergone a hematopoietic stem cell transplant. Several PCR techniques were used among the included studies. The sensitivity and specificity of PCR for the diagnosis of IA varied according to the interpretative criteria used to define a test as positive. The mean sensitivity and specificity were 80.5% (95% CI; 73.0 to 86.3) and 78.5% (67.8 to 86.4) for a single positive test result, and 58.0% (36.5 to 76.8) and 96.2% (89.6 to 98.6) for two consecutive positive test results.
AUTHORS' CONCLUSIONS
PCR shows moderate diagnostic accuracy when used as screening tests for IA in high-risk patient groups. Importantly the sensitivity of the test confers a high negative predictive value (NPV) such that a negative test allows the diagnosis to be excluded. Consecutive positives show good specificity in diagnosis of IA and could be used to trigger radiological and other investigations or for pre-emptive therapy in the absence of specific radiological signs when the clinical suspicion of infection is high. When a single PCR positive test is used as diagnostic criterion for IA in a population of 100 people with a disease prevalence of 13.0% (overall mean prevalence), three people with IA would be missed (sensitivity 80.5%, 19.5% false negatives), and 19 people would be unnecessarily treated or referred for further tests (specificity of 78.5%, 21.5% false positives). If we use the two positive test requirement in a population with the same disease prevalence, it would mean that six IA people would be missed (sensitivity 58.0%, 42.1% false negatives) and three people would be unnecessarily treated or referred for further tests (specificity of 96.2%, 3.8% false positives). Galactomannan and PCR have good NPV for excluding disease but the low prevalence of disease limits the ability to rule in a diagnosis. The biomarkers are detecting different aspects of disease and the combination of both together is likely to be more useful.
Topics: Aspergillosis; Cohort Studies; Data Accuracy; False Negative Reactions; False Positive Reactions; Humans; Immunocompromised Host; Opportunistic Infections; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity
PubMed: 26424726
DOI: 10.1002/14651858.CD009551.pub3 -
Polish Journal of Radiology 2021To assess differentiating features between bacterial, , and skull base osteomyelitis (SBO) with regard to clinical presentation and imaging appearances.
PURPOSE
To assess differentiating features between bacterial, , and skull base osteomyelitis (SBO) with regard to clinical presentation and imaging appearances.
MATERIAL AND METHODS
A literature search was performed in April 2020 for studies on SBO with a minimum sample size of 10 patients. Studies that reported presenting symptoms, cross-sectional imaging findings, complications, and mortality were included in the analysis. The quality of included articles was tested using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. A data extraction form was used to retrieve relevant parameters from each of the articles.
RESULTS
Thirteen articles were included in the final analysis. Diabetes mellitus was the most common predisposing factor (12.5-91.0%). Presenting complaints in all bacterial SBO studies were otogenic, while fungal SBO patients had nasal/ocular complaints. Rates of mortality and surgical intervention in the fungal group were 50-100% and 50%, respectively, as compared to the bacterial group - 7-87% and 10%, respectively. On imaging, the site of initial infection in bacterial SBO was the external auditory canal, while in fungal SBO it was the paranasal sinus. The incidence of orbital extension was < 5% in bacterial and 44-70% in fungal SBO, among which had rates of 65-70%. Bone erosion was less extensive in bacterial SBO, and the patterns differed. The highest incidence of vascular involvement and non-enhancing lesions (23-36%) was seen in showed highest sino-cranial extension (52-55%) and homogenous bright enhancement.
CONCLUSIONS
Systematic analysis of the clinico-radiological parameters in each of the studies revealed differences in presentation, clinical course, extension, bone erosion, and enhancement.
PubMed: 34136049
DOI: 10.5114/pjr.2021.106470 -
The Journal of Infection Mar 2013To describe the pathogenesis, clinical presentation, cerebrospinal fluid findings and outcome of Aspergillus meningitis, meningoencephalitis and arachnoiditis. (Review)
Review
OBJECTIVES
To describe the pathogenesis, clinical presentation, cerebrospinal fluid findings and outcome of Aspergillus meningitis, meningoencephalitis and arachnoiditis.
METHODS
A case of Aspergillus meningitis is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of Aspergillus meningitis described between January 1973 and December 2011.
RESULTS
Ninety-three cases (including the one described herein) of Aspergillus meningitis were identified. Fifty-two (55.9%) were in individuals without any predisposing factor or known causes of immunosuppression. Acute and chronic meningitis was diagnosed in 65.6% of patients and meningoencephalitis in 24.7% of them with the remaining presenting with spinal arachnoiditis and ventriculitis. Cerebrospinal fluid cultures for Aspergillus spp. were positive in about 31% of cases and the galactomannan antigen test in 87%. Diagnosis during life was achieved in 52 patients (55.9%) with a case fatality rate of 50%. The overall case fatality rate was 72.1%.
CONCLUSIONS
Aspergillus meningitis may occur in both immunocompetent and immunocompromised patients and run an acute or chronic course. The findings of this systematic review extend the information on this life-threatening infection and could assist physicians in achieving an improved outcome.
Topics: Adult; Aspergillosis; Aspergillus flavus; Central Nervous System; Cerebrospinal Fluid; Female; Humans; Immunocompromised Host; Male; Meningitis, Fungal
PubMed: 23178421
DOI: 10.1016/j.jinf.2012.11.003