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3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
Diagnostics (Basel, Switzerland) Aug 2023The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is crucial since most clinical signs are not specific to invasive fungal... (Review)
Review
The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is crucial since most clinical signs are not specific to invasive fungal infections. To detect an IPA, different criteria should be considered. Next to host factors and radiological signs, microbiological criteria should be fulfilled. For microbiological diagnostics, different methods are available. Next to the conventional culture-based approaches like staining and culture, non-culture-based methods can increase sensitivity and improve time-to-result. Besides fungal biomarkers, like galactomannan and (1→3)-β-D-glucan as nonspecific tools, molecular-based methods can also offer detection of resistance determinants. The detection of novel biomarkers or targets is promising. In this review, we evaluate and discuss the value of non-culture-based microbiological methods (galactomannan, (1→3)-β-D-glucan, PCR, new biomarker/targets) for diagnosing IPA in ICU patients.
PubMed: 37627977
DOI: 10.3390/diagnostics13162718 -
The Korean Journal of Internal Medicine Jan 2024Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the... (Review)
Review
Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the subsequent long-term repercussions have drawn increased attention due to their profound clinical and socioeconomic impacts. A primary obstacle to its comprehensive study has been its marked heterogeneity. The disease presents a spectrum of clinical manifestations which encompass tracheobronchial stenosis, bronchiectasis, granulomas with fibrosis, cavitation with associated aspergillosis, chronic pleural diseases, and small airway diseases-all persistent consequences of PTLD. The spectrum of symptoms a patient may experience varies based on the severity of the initial infection and the efficacy of the treatment received. As a result, the long-term management of PTLD necessitates a detailed and specific approach, addressing each manifestation individually-a tailored strategy. In the immediate aftermath (0-12 months after anti-TB chemotherapy), there should be an emphasis on monitoring for relapse, tracheobronchial stenosis, and smoking cessation. Subsequent management should focus on addressing hemoptysis, managing infection including aspergillosis, and TB-associated chronic obstructive pulmonary disease or restrictive lung function. There remains a vast expanse of knowledge to be discovered in PTLD. This review emphasizes the pressing need for comprehensive, consolidated guidelines for management of patients with PTLD.
Topics: Humans; Tuberculosis, Pulmonary; Constriction, Pathologic; Lung Diseases; Chronic Disease; Tuberculosis; Aspergillosis
PubMed: 38225822
DOI: 10.3904/kjim.2023.395 -
The Lancet Regional Health. Western... Nov 2023New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical...
BACKGROUND
New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice.
METHODS
The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM).
FINDINGS
Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non- species complex. Azole-resistance was present in 3/46 (6.5%) of isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028).
INTERPRETATION
IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non- complex isolates and 6.5% azole-resistance rate amongst necessitates accurate species identification and susceptibility testing for optimal patient outcomes.
FUNDING
This work is unfunded. All authors' financial disclosures are listed in detail at the end of the manuscript.
PubMed: 37701716
DOI: 10.1016/j.lanwpc.2023.100888 -
Antibiotics (Basel, Switzerland) Jul 2023Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary...
Clinical and Microbiological Outcomes and Follow-Up of Secondary Bacterial and Fungal Infections among Critically Ill COVID-19 Adult Patients Treated with and without Immunomodulation: A Prospective Cohort Study.
BACKGROUND
Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary infections among critically ill COVID-19 adult patients treated with/without immunomodulation.
METHODS
A prospective observational cohort study was performed between 2020 and 2022 at a single ICU. The diagnosis and severity classification were established by the ECDC and WHO criteria, respectively. Eligible patients were included consecutively at admission, and followed for +30 days post-inclusion. Bloodstream-infections (BSIs), ventilator-associated bacterial pneumonia (VAP), and COVID-19-associated invasive pulmonary aspergillosis (CAPA) were defined according to international guidelines. Patient stratification was performed by immunomodulatory therapy administration (dexamethasone, tocilizumab, baricitinib/ruxolitinib). The primary outcome was any microbiologically confirmed major infectious complication, secondary outcomes were invasive mechanical ventilation (IMV) requirement and all-cause mortality.
RESULTS
Altogether, 379 adults were included. At baseline, 249/379 (65.7%) required IMV and 196/379 (51.7%) had a cytokine storm. At +30 days post-inclusion, the rate of any microbiologically confirmed major infectious complication was 151/379 (39.8%), IMV requirement and all-cause mortality were 303/379 (79.9%) and 203/379 (53.6%), respectively. There were no statistically significant outcome differences after stratification. BSI, VAP, and CAPA episodes were mostly caused by (27/124, 22.1%), (26/91, 28.6%), and (20/20, 100%), respectively. Concerning the primary outcome, Kaplan-Meier analysis showed similar probability distributions between the treatment subgroups (118/299, 39.5% vs. 33/80, 41.3%, log-rank = 0.22), and immunomodulation was not retained as its independent predictor in multivariate logistic regression.
CONCLUSIONS
Secondary infections among critically ill COVID-19 adult patients represent a relevant burden, probably irrespective of immunomodulatory treatment.
PubMed: 37508292
DOI: 10.3390/antibiotics12071196 -
Allergology International : Official... Oct 2023Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and... (Review)
Review
Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic.
Topics: Child; Adult; Humans; Antifungal Agents; Asthma; Azithromycin; Bronchiectasis; Adrenal Cortex Hormones
PubMed: 37544851
DOI: 10.1016/j.alit.2023.07.003 -
American Journal of Respiratory and... Aug 2023Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness...
Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases ( = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis ( = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza ( = 3) and COVID-19 ( = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Autopsy; COVID-19; Influenza, Human; Intensive Care Units; Invasive Pulmonary Aspergillosis; Retrospective Studies; Hospital Mortality
PubMed: 37311243
DOI: 10.1164/rccm.202208-1570OC -
Seminars in Respiratory and Critical... Feb 2024Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by hyphae invading... (Review)
Review
Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.
Topics: Humans; Invasive Pulmonary Aspergillosis; Antifungal Agents; Aspergillus; Immunocompromised Host; Triazoles
PubMed: 38211628
DOI: 10.1055/s-0043-1777769 -
American Journal of Respiratory and... Aug 2023
Topics: Humans; Influenza, Human; COVID-19; Pulmonary Aspergillosis; Invasive Pulmonary Aspergillosis
PubMed: 37348113
DOI: 10.1164/rccm.202306-1022ED -
Journal of Fungi (Basel, Switzerland) Dec 2023The most common fungal infections reported from the Caribbean include dermatophytosis, candidiasis, pneumocystis, aspergillosis, histoplasmosis, and cryptococcosis. The... (Review)
Review
The most common fungal infections reported from the Caribbean include dermatophytosis, candidiasis, pneumocystis, aspergillosis, histoplasmosis, and cryptococcosis. The Caribbean is hyperendemic for histoplasmosis, with high population exposures. Fungal infections are a significant public health problem in the Caribbean, with rates varying depending on the specific country or region. In Trinidad and Tobago, the fungal burden accounts for 3.3% of the 1.4 million population, while in Jamaica, with a population of 2.9 million, over 57,600 people suffer from fungal infections each year. A study in the Dominican Republic estimated that approximately 221,027 (2%) of over 10 million people have a serious fungal infection. Fungal infections accounts for 21.9% of all skin infections in Haiti. The diagnosis of fungal infections in the Caribbean can be challenging, as access to laboratory testing and specialized medical services is limited in many areas. Access to antifungal medications can also be a challenge in some areas, and antifungal resistance has been reported.
PubMed: 38132779
DOI: 10.3390/jof9121177