Seminars in respiratory and critical care medicine最新文献

{"title":"The Spectrum of Pulmonary Aspergillosis.","authors":"Eva Van Braeckel, Oliver A Cornely","doi":"10.1055/s-0043-1778126","DOIUrl":"10.1055/s-0043-1778126","url":null,"abstract":"","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal Therapies for Aspergillus spp.: Present and Future.","authors":"Gregory A Eschenauer","doi":"10.1055/s-0043-1776776","DOIUrl":"10.1055/s-0043-1776776","url":null,"abstract":"<p><p>Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug-drug interactions, pharmacokinetic variability, and emerging resistance. While the echinocandins are safe agents and may have a role in combination therapy, they are unproven as monotherapy. Amphotericin B preparations are toxic and require intensive monitoring. Finally, aspergillosis continues to be a disease conferring substantial morbidity and mortality, and clinical trials have not identified a therapeutic approach clearly associated with improved outcomes. As a result, there is a great need for new options in the treatment of invasive aspergillosis. Ideally, such options would be safe, have high oral bioavailability, have favorable pharmacokinetics to sequestered sites and retain activity against azole-resistant isolates. Reassuringly, there is a robust pipeline of novel therapies in development. Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis. Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic Strategies for Severe Community-Acquired Pneumonia","authors":"Matteo Bassetti, Daniele R. Giacobbe, Laura Magnasco, Alberto Fantin, Antonio Vena, Nadia Castaldo","doi":"10.1055/s-0043-1778641","DOIUrl":"https://doi.org/10.1055/s-0043-1778641","url":null,"abstract":"<p>Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) patients have not shown significant improvement. Delayed admission to the ICU is a major risk factor for higher mortality. Apart from choosing the appropriate site of care, prompt and appropriate antibiotic therapy significantly affects the prognosis of sCAP. Treatment regimens involving ceftaroline or ceftobiprole are currently considered the best options for managing patients with sCAP. Additionally, several other molecules, such as delafloxacin, lefamulin, and omadacycline, hold promise as therapeutic strategies for sCAP. This review aims to provide a comprehensive summary of the key challenges in managing adults with severe CAP, focusing on essential aspects related to antibiotic treatment and investigating potential strategies to enhance clinical outcomes in sCAP patients.</p> ","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.","authors":"Matthias J Neuböck, Gunar Günther, Aleksandra Barac, Jesper R Davidsen, Christian B Laursen, Ritesh Agarwal, Inderpaul S Sehgal, Christoph Lange, Helmut J F Salzer","doi":"10.1055/s-0043-1776913","DOIUrl":"10.1055/s-0043-1776913","url":null,"abstract":"<p><p>Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of <i>Aspergillus</i> species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspergillus and the Lung.","authors":"Iris Janssens, Bart N Lambrecht, Eva Van Braeckel","doi":"10.1055/s-0043-1777259","DOIUrl":"10.1055/s-0043-1777259","url":null,"abstract":"<p><p>The filamentous fungus <i>Aspergillus</i> causes a wide spectrum of diseases in the human lung, with <i>Aspergillus fumigatus</i> being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of <i>Aspergillus</i> in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Pulmonary Aspergillosis: Clinical Presentation and Management.","authors":"Terry J Evans, AbdulAzeez Lawal, Chris Kosmidis, David W Denning","doi":"10.1055/s-0043-1776914","DOIUrl":"10.1055/s-0043-1776914","url":null,"abstract":"<p><p>Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of <i>Aspergillus</i> organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on <i>Aspergillus</i> immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of <i>Aspergillus</i> adaptation in the lung environment, the contribution of non-<i>fumigatus</i> <i>Aspergillus</i> species, and the role of new antifungal agents, immunotherapy, and combination therapy.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal Resistance in Pulmonary Aspergillosis.","authors":"Paul E Verweij, Yinggai Song, Jochem B Buil, Jianhua Zhang, Willem J G Melchers","doi":"10.1055/s-0043-1776997","DOIUrl":"10.1055/s-0043-1776997","url":null,"abstract":"<p><p>Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). <i>Aspergillus fumigatus</i> represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various <i>Aspergillus</i> diseases. These morphotypes determine the ease by which <i>A. fumigatus</i> can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic <i>Aspergillus</i> diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various <i>Aspergillus</i> diseases may help to improve diagnostic and therapeutic strategies.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiological Diagnosis of Pulmonary Aspergillus Infections.","authors":"Robina Aerts, Simon Feys, Toine Mercier, Katrien Lagrou","doi":"10.1055/s-0043-1776777","DOIUrl":"10.1055/s-0043-1776777","url":null,"abstract":"<p><p>As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided. Current diagnostic possibilities are expanding, and are mainly driven by enzyme immunoassays and lateral flow device tests for the detection of <i>Aspergillus</i> antigens. Most of these tests are directed towards similar antigens, but new antibodies towards different targets are under development. For chronic forms of pulmonary aspergillosis, anti-<i>Aspergillus</i> IgG antibodies and precipitins remain the cornerstone. More studies on the possibilities and limitations of molecular testing including targeting resistance markers are ongoing. Also, metagenomic next-generation sequencing is expanding our future possibilities. It remains important to combine different test results and interpret them in the appropriate clinical context to improve performance. Test performances may differ according to the patient population and test results may be influenced by timing, the tested matrix, and prophylactic and empiric antifungal therapy. Despite the increasing armamentarium, a simple blood or urine test for the diagnosis of aspergillosis in all patient populations at-risk is still lacking. Research on diagnostic tools is broadening from a pathogen focus on biomarkers related to the patient and its immune system.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment.","authors":"Jannes Heylen, Yuri Vanbiervliet, Johan Maertens, Bart Rijnders, Joost Wauters","doi":"10.1055/s-0043-1777769","DOIUrl":"10.1055/s-0043-1777769","url":null,"abstract":"<p><p>Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by <i>Aspergillus</i> 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.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Aspergillosis in People with Cystic Fibrosis.","authors":"C Schwarz, P N Eschenhagen, J G Mainz, T Schmidergall, H Schuette, E Romanowska","doi":"10.1055/s-0043-1777267","DOIUrl":"10.1055/s-0043-1777267","url":null,"abstract":"<p><p>In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by <i>Aspergillus</i> spp. The most common organisms from this genus detected from respiratory cultures are <i>Aspergillus fumigatus</i> and <i>Aspergillus terreus</i>, followed by <i>Aspergillus flavus</i>, <i>Aspergillus niger</i>, and <i>Aspergillus nidulans</i>. These species have been identified to be both chronic colonizers and sources of active infection and may negatively impact lung function in people with CF. This review article discusses definitions of aspergillosis, challenges in clinical practice, and current literature available for laboratory findings, clinical diagnosis, and treatment options for pulmonary diseases caused by <i>Aspergillus</i> spp. in people with CF.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}