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The Journal of Antimicrobial... Apr 2024Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review...
INTRODUCTION
Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children.
OBJECTIVES
To evaluate the concentration-efficacy relationship, concentration-toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children.
METHODS
We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0-18 years. Review articles, case series of
RESULTS
In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (Cmax/MIC) of 25-50 for optimal efficacy and an AUC24 of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5-10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L.
CONCLUSIONS
While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.
Topics: Child; Animals; Humans; Infant, Newborn; Antifungal Agents; Drug Monitoring; Amphotericin B; Candidiasis, Invasive
PubMed: 38252921
DOI: 10.1093/jac/dkae003 -
BMC Infectious Diseases Jan 2024With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common....
BACKGROUND/OBJECTIVE
With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals.
METHODS
A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review.
RESULT
The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%).
CONCLUSION
Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.
Topics: Humans; Coinfection; Retrospective Studies; Pulmonary Aspergillosis; Cryptococcosis; Aspergillosis
PubMed: 38229026
DOI: 10.1186/s12879-024-09014-8 -
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 -
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 -
Le Infezioni in Medicina 2023Chronic pulmonary aspergillosis (CPA) is a progressive, debilitating clinical condition associated with significant morbidity. Surgery is the mainstay of treatment for...
Chronic pulmonary aspergillosis (CPA) is a progressive, debilitating clinical condition associated with significant morbidity. Surgery is the mainstay of treatment for life-threatening hemoptysis in symptomatic patients with simple aspergillomas. However, in patients with chronic cavitary pulmonary aspergillosis, surgical removal of aspergillomas is fraught with difficulty due to debilitating nature of the illness. Here we present a case showcasing the utility of intrabronchial voriconazole instillation in controlling hemoptysis in a patient unfit for surgery followed by systematic review of literature involving 11 clinical studies after screening a total of 5572 studies from PubMed and Google Scholar database. Data gathered from these studies addresses the concerns regarding the efficacy, safety of the procedure as well as draws attention regarding several lacunae in our existing knowledge. A 53-year-old male with chronic pulmonary aspergillosis who had recurrent episodes of hemoptysis despite bronchial artery embolization and was unfit for surgery due to limited lung reserve, patient underwent single session of intrabronchial voriconazole instillation which resulted in dramatic symptomatic and radiological improvement. Intrabronchial antifungal instillation may be a safe and effective option for hemoptysis control in patients with chronic pulmonary aspergillosis.
PubMed: 38075417
DOI: 10.53854/liim-3104-17 -
Lung India : Official Organ of Indian... 2023The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating...
BACKGROUND
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma.
METHODS
We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression.
RESULTS
Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence.
CONCLUSIONS
There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.
PubMed: 37961961
DOI: 10.4103/lungindia.lungindia_69_23 -
Transplantation Apr 2024Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant.
METHODS
We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant.
RESULTS
We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis.
CONCLUSIONS
Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.
Topics: Humans; Risk Factors; Organ Transplantation; Aspergillosis; Cytomegalovirus Infections; Invasive Fungal Infections; Candidiasis, Invasive; Transplant Recipients; Candidiasis
PubMed: 37953478
DOI: 10.1097/TP.0000000000004871 -
BMC Pulmonary Medicine Oct 2023Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA.
METHODS
We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks' funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I statistic were used to test the heterogeneity.
RESULTS
Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks's test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value < 0.001. The PLR and NLR for IgE were 7.80 (5.03,12.10) and 0.19 (0.13,0.27), while for IgG were 3.45 (2.40,4.96) and 0.09 (0.05,0.17). The combined diagnostic odds ratio and diagnostic score were 41.49 (26.74,64.36) and3.73 (3.29,4.16) for IgE, respectively, and were 38.42 (19.23,76.79) and 3.65 (2.96,4.34) for IgG.
CONCLUSION
The sensitivity for IgG diagnosing ABPA is higher than IgE, while the specificity for IgE is higher. IgG might be able to play a more important role in filtering ABPA patients.
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Antibodies, Fungal; Immunoassay; Immunoglobulin E; Immunoglobulin G
PubMed: 37798745
DOI: 10.1186/s12890-023-02620-3 -
Chest Mar 2024Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
Prevalence, Risk Factors, Clinical Features, and Outcome of Influenza-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Systematic Review and Meta-Analysis.
BACKGROUND
Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA.
STUDY QUESTION
What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients?
STUDY DESIGN AND METHODS
Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models.
RESULTS
We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2% (331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95% CI, 1.7-13.8; I = 45%), harbored a hematogenous malignancy (OR, 2.5; 95% CI, 1.5-4.1; I = 0%), were immunocompromised (OR, 2.2; 95% CI, 1.6-3.1; I = 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95% CI, 1.4-4.3; I = 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95% CI, 1.8-3.8; I = 0%).
INTERPRETATION
IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm.
TRIAL REGISTRY
International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Critical Illness; Influenza, Human; Prevalence; Pulmonary Aspergillosis; Risk Factors
PubMed: 37742914
DOI: 10.1016/j.chest.2023.09.019 -
Substance Abuse Jul 2023The prevalence of marijuana use and its derivatives has surged over the past century, largely due to increasing legalization globally. Despite arguments advocating its... (Review)
Review
BACKGROUND
The prevalence of marijuana use and its derivatives has surged over the past century, largely due to increasing legalization globally. Despite arguments advocating its benefits, marijuana smoking exposes the lungs to harmful combustion byproducts, leading to various respiratory issues such as asthma, pneumonia, emphysema, and chronic obstructive pulmonary disease.
METHODS
We embarked on an extensive literature search, utilizing PubMed/Medline, Scopus, Web of Science, and Google Scholar databases, identifying 200 studies. After the elimination of duplicates, and meticulous review of abstracts and full texts, 55 studies were included in our analysis.
RESULTS
Current literature demonstrates that marijuana use negatively impacts lung function, triggering symptoms like chronic cough, sputum production, and wheezing, and diminishing FEV1/FVC ratio in spirometry tests. Moreover, prolonged or chronic marijuana use augments the risk of respiratory function impairment. While the carcinogenic effects of marijuana are still contested, a weak correlation between marijuana use and lung cancer has been observed in some studies. Additionally, instances of other pathologies linked to marijuana use have been reported, including the development of COPD, pulmonary bullae, spontaneous pneumothorax, pleuritic pain, chronic pulmonary aspergillosis, hemoptysis, and pulmonary Langerhans cell histiocytosis.
CONCLUSIONS
The evidence underscores that marijuana use is detrimental to respiratory health. In light of the escalating trend of marijuana use, particularly among the youth, it is imperative to advocate public health messages discouraging its consumption.
PubMed: 37728136
DOI: 10.1177/08897077231186228