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Frontiers in Cellular and Infection... 2022Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a... (Review)
Review
PURPOSE
Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD.
METHODS
We performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review.
RESULTS
IFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD.
CONCLUSION
Taken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions.
Topics: Humans; Triazoles; Invasive Fungal Infections; Nitriles; Antifungal Agents; Aspergillosis; Mucormycosis; Candidiasis, Invasive
PubMed: 36530445
DOI: 10.3389/fcimb.2022.1049959 -
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 -
Italian Journal of Pediatrics Mar 2023Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify... (Review)
Review
Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify this issue, a literature search was performed through MEDLINE/PubMed database to describe current risk factors and diagnostic, therapeutic and prophylactic tools for invasive pulmonary aspergillosis (IPA) in the paediatric age. Observational studies and clinical trials regarding diagnosis, treatment and prophylaxis were considered, and results were summarised. Five clinical trials and 25 observational studies (4453 patients) were included.Haematological malignancies, previous organ transplant and other primary or acquired immunodeficiency were identified as risk factors for IPA in children.Current diagnostic criteria distinguish between "proven", "probable" and "possible" disease. Consecutive galactomannan assays have good sensitivity and specificity, especially when performed on broncho-alveolar lavage. At the same time, β-D-glucan should not be used since cut-off in children is unclear. PCR assays cannot currently be recommended for routine use.Voriconazole is the recommended first-line agent for IPA in children older than 2 years of age. Liposomal amphotericin B is preferred in younger patients or cases of intolerance to voriconazole. Its plasma concentrations should be monitored throughout the treatment. The optimal duration of therapy has yet to be determined. Posaconazole is the preferred prophylactic agent in children older than 13 years old, whereas oral voriconazole or itraconazole are the drugs of choice for those between 2-12 years. Further good-quality studies are warranted to improve clinical practice.
Topics: Humans; Child; Child, Preschool; Adolescent; Invasive Pulmonary Aspergillosis; Voriconazole; Pulmonary Aspergillosis; Sensitivity and Specificity; Immunocompromised Host; Mannans; Antifungal Agents
PubMed: 36978151
DOI: 10.1186/s13052-023-01440-9 -
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 -
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 -
Cureus Mar 2022The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood... (Review)
Review
The prevalence, incidence, and characteristics of bacterial infections in patients infected with severe acute respiratory syndrome coronavirus 2 are not well understood and have been raised as an important knowledge gap. Therefore, our study focused on the most common opportunistic infections/secondary infections/superinfections in coronavirus disease 2019 (COVID-19) patients. This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eligible studies were identified using PubMed/Medline since inception to June 25, 2021. Studies meeting the inclusion criteria were selected. Statistical analysis was conducted in Review Manager 5.4.1. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported as inverse variance and the corresponding 95% confidence interval. We screened 701 articles comprising 22 cohort studies which were included for analysis. The pooled prevalence of opportunistic infections/secondary infections/superinfections was 16% in COVID-19 patients. The highest prevalence of secondary infections was observed among viruses at 33%, followed by bacteria at 16%, fungi at 6%, and 25% among the miscellaneous group/wrong outcome. Opportunistic infections are more prevalent in critically ill patients. The isolated pathogens included Epstein-Barr virus, , , , , and invasive pulmonary aspergillosis. Large-scale studies are required to better identify opportunistic/secondary/superinfections in COVID-19 patients.
PubMed: 35505698
DOI: 10.7759/cureus.23687 -
The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Current Fungal Infection Reports 2023Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids... (Review)
Review
PURPOSE OF REVIEW
Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids on mortality and visual outcome in different fungal diseases.
RECENT FINDINGS
Corticosteroids are a risk factor of aspergillosis for patients who have COVID-19, and they also led to a worse outcome. Similarity, corticosteroids are a risk factor for candidemia and mucormycosis. Some researchers reported that using topical corticosteroid in keratitis was associated with worse visual outcome if fungal keratitis. Some studies showed that corticosteroids are linked to a negative outcome for non-HIV patients with pneumonia (PCP), in contrast to those with HIV and PCP.
SUMMARY
In 59 references, we found that corticosteroid therapy showed a worse clinical outcome in invasive aspergillosis (IA) (HR: 2.50, 95%CI: 1.89-3.31, < 0.001) and chronic pulmonary aspergillosis (CPA) (HR: 2.74, 95%CI: 1.48-5.06, = 0.001), PCP without HIV infection (OR: 1.29, 95%CI: 1.09-1.53, = 0.003), invasive candidiasis and candidaemia (OR: 2.13, 95%CI: 1.85-2.46, < 0.001), mucormycosis (OR: 4.19, 95%CI: 1.74-10.05, = 0.001) and early in the course of fungal keratitis (OR: 2.99, 95%CI: 1.14-7.84, = 0.026). There was equivocal outcome in cryptococcal meningoencephalitis in AIDS and primary coccidioidomycosis, while corticosteroid therapy showed a better outcome in PCP in HIV-infected patients (RR: 0.62, 95%CI: 0.46-0.83, =0.001) and fungal keratitis patients after keratoplasty surgery (OR: 0.01, 95%CI: 0.00-0.41, = 0.041) and probably in cryptococcal meningoencephalitis in non-immunocompromised patients. A sub-analysis in invasive aspergillosis and CPA showed that use of more than 2 mg/kg/day of prednisolone equivalents per day is a significant factor in increasing mortality (HR: 2.94, 95%CI: 2.13-4.05, < 0.001). Corticosteroid therapy during invasive fungal disease was usually associated with a slightly or greatly increased mortality or worse visual outcome (in fungal keratitis), with two disease exceptions. Avoiding the addition of corticosteroids, or minimising dose and duration in those who require them, is likely to improve the outcome of most life- and vision-threatening fungal diseases. This review provides a cornerstone for further research in exploring the accuracy of suitable dose and duration of corticosteroids treatment in fungal diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12281-023-00456-2.
PubMed: 36852004
DOI: 10.1007/s12281-023-00456-2 -
Oral and Maxillofacial Surgery Sep 2022With the advent of coronavirus disease (COVID-19) pandemic, a wide range of life-threatening maxillofacial fungal coinfections have also been observed in patients. We... (Review)
Review
With the advent of coronavirus disease (COVID-19) pandemic, a wide range of life-threatening maxillofacial fungal coinfections have also been observed in patients. We conducted this systematic review to collate and evaluate the data to enable clinicians to understand the disease pattern and types of mycosis and provide meticulous management of these infections in COVID-19 patients. The review was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A systematic electronic literature search was conducted on major databases using keywords in combination with Boolean Operators. Manuscripts discussing cases of maxillofacial fungal infections in COVID-19 patients were included. A total of 11 studies were systematically reviewed to assess the fungal coinfections in COVID-19 patients. Twenty-one cases of mucormycosis, 58 of candidiasis, and 1 each of aspergillosis and mixed infection were observed in the region of head and neck. Significant increase in invasive fungal infection is evident in patients suffering from COVID-19 which could be due to immunosuppression and other pre-existing comorbidities. Early diagnosis and intervention like systemic antifungals or surgical debridement is mandatory to reduce morbidity and mortality.
Topics: COVID-19; Coinfection; Humans; Mycoses; Pandemics
PubMed: 34622312
DOI: 10.1007/s10006-021-01010-5 -
Health Science Reports Sep 2022COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19...
COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19 associated mucormycosis (CAM) and aspergillosis (CAA), have recently been highly acquainted by many worldwide cases. Two immune response deteriorating factors are considered to be responsible for immunosuppression: comorbidities and medication. Due to unlike infection sites and patterns, CAM and CAA-associated factors deflect a few degrees of proximity, and the present study is for its assessment. The study evaluated 351 CAM cases and 191 CAA cases retrieved from 65 and 53 articles based on inclusion criteria, respectively. Most of the CAM reported from India and CAA were from four South-European and West-European neighbor countries. The mean ages of CAM and CAA were 52.72 ± 13.74 and 64.81 ± 11.14, correspondingly. Mortality of CAA (56.28%) was two times greater than CAM (26.02%). Nevertheless, the count of diabetes cases was very high in CAM compared to CAA. The main comorbidities of CAM were diabetes (nearly 80%) and hypertension (more than 38%). All noticeable complications were higher in CAA except diabetes, and these were diabetes (34.55%), hypertension (45.03%), and obesity (18.32%). Moreover, pre-existing respiratory complications like asthma and chronic obstructive pulmonary disease are visible in CAA. The uses of steroids in CAM and CAA were nearly 70% and 66%, respectively. Almost one-fourth of CAA cases were reported using immunosuppressant monoclonal antibodies, whereas only 7.69% were for CAM. The overall finding highlights diabetes, hypertension, and steroids as the risk factors for CAM, whereas obesity, chronic pulmonary disease, and immunosuppressants for CAA.
PubMed: 36000078
DOI: 10.1002/hsr2.789