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Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.
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Tratamiento Farmacológico de COVID-19 , COVID-19/patología , COVID-19/virología , Senescencia Celular/efectos de los fármacos , Terapia Molecular Dirigida , SARS-CoV-2/patogenicidad , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Animales , COVID-19/complicaciones , Línea Celular , Cricetinae , Dasatinib/farmacología , Dasatinib/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Quercetina/farmacología , Quercetina/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Trombosis/complicaciones , Trombosis/inmunología , Trombosis/metabolismoRESUMEN
BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500â IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.
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Aspergilosis Broncopulmonar Alérgica , Aspergilosis Pulmonar Invasiva , Adulto , Niño , Humanos , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Inmunoglobulina E , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Itraconazol/uso terapéutico , Micología , PrednisolonaRESUMEN
PURPOSE OF REVIEW: Post-tuberculosis lung disease (PTLD) is an increasingly recognized and debilitating consequence of pulmonary tuberculosis (PTB). In this review, we provide a comprehensive overview of PTLD with airflow obstruction (PTLD-AFO), focusing on its burden, pathophysiology, clinical manifestations, diagnostic methods, and management strategies. RECENT FINDINGS: The relationship between PTLD and airflow obstruction is complex and multifactorial. Approximately 60% of the patients with PTLD have some spirometric abnormality. Obstruction is documented in 18-22% of PTLD patients. The host susceptibility and host response to mycobacterium drive the pathogenic mechanism of PTLD. A balance between inflammatory, anti-inflammatory, and fibrotic pathways decides whether an individual with PTB would have PTLD after microbiological cure. An obstructive abnormality in PTLD-AFO is primarily due to destruction of bronchial walls, aberrant healing, and reduction of mucosal glands. The most common finding on computed tomography (CT) of thorax in patients with PTLD-AFO is bronchiectasis and cavitation. Therefore, the 'Cole's vicious vortex' described in bronchiectasis applies to PTLD. A multidisciplinary approach is required for diagnosis and treatment. The disability-adjusted life-years (DALYs) attributed to PTLD represent about 50% of the total estimated burden of DALYs due to tuberculosis (TB). Patients with PTLD require comprehensive care that includes psychosocial support, pulmonary rehabilitation, and vaccination against respiratory pathogens. In the absence of trials evaluating different treatments for PTLD-AFO, therapy is primarily symptomatic. SUMMARY: PTLD with airflow obstruction has considerable burden and causes a significant morbidity and mortality. However, many aspects of PTLD-AFO still need to be answered. Studies are required to evaluate different phenotypes, especially concerning Aspergillus -related complications. The treatment should be personalized based on the predominant phenotype of airflow obstruction. Extensive studies to understand the exact burden, pathogenesis, and treatment of PTBLD-AFO are needed.
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Bronquiectasia , Enfermedades Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Tuberculosis Pulmonar , Humanos , Pulmón , Enfermedades Pulmonares/complicaciones , Bronquiectasia/complicacionesRESUMEN
PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.
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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 Aspergillus 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.
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Enfermedades Pulmonares , Aspergilosis Pulmonar , Tuberculosis , Humanos , Enfermedad Crónica , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/terapia , Pulmón , Enfermedades Pulmonares/complicaciones , Tuberculosis/complicaciones , Infección PersistenteRESUMEN
Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients.
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In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'.
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Nitroimidazoles , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Rifampin , Antituberculosos/uso terapéutico , Linezolid/uso terapéutico , Austria , Suiza , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Alemania , Combinación de MedicamentosRESUMEN
INTRODUCTION: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria. METHODS: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI_management_capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring. RESULTS: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites. CONCLUSION: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.
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Antifúngicos , Infecciones Fúngicas Invasoras , Humanos , Antifúngicos/uso terapéutico , Austria/epidemiología , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , Hongos , Accesibilidad a los Servicios de SaludRESUMEN
BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.
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Tuberculosis , Humanos , Incidencia , Estudios Transversales , Somalia , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Europa (Continente)/epidemiologíaRESUMEN
BACKGROUND: The chronic pulmonary aspergillosis network (CPAnet) has recently proposed definitions for treatment outcomes in CPA. However, these definitions need to be validated. Herein, we evaluate the agreement between the existing and the CPAnet definitions for response assessment. METHODS: We enrolled consecutive treatment-naïve CPA subjects (between January 2021 and June 2021) who received six months of itraconazole therapy and followed them for an additional six months after treatment discontinuation. We retrospectively applied the CPAnet criteria and compared the agreement between the existing and the CPAnet criteria for response assessment (primary objective). We also assessed if adding weight loss (> 5% from baseline) as a component improved the performance of the CPAnet criteria. RESULTS: We included 43 (mean age, 47.4 years) CPA subjects. The existing and the CPAnet criteria categorized 29 (67.4%) and 30 (69.8%) subjects as treatment success, respectively, at treatment completion. There was substantial (kappa = 0.73; p < 0.0001) agreement between the two definitions. However, both criteria did not identify eight subjects requiring treatment re-initiation within three months. There was an increment in the sensitivity of both criteria (by 36%) for identifying treatment failure after incorporating ≥ 5% weight loss as an element of worsening. CONCLUSION: The CPAnet definitions correctly categorized treatment outcomes in most cases of CPA. The addition of weight change would further enhance the performance of the CPAnet treatment outcome definitions.
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Aspergilosis Pulmonar , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad Crónica , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Resultado del Tratamiento , Pérdida de PesoRESUMEN
This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Dermatología , Gastroenterología , Tuberculosis Latente , Neumología , Reumatología , Humanos , Antirreumáticos/uso terapéutico , Austria , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Tuberculosis Latente/tratamiento farmacológico , Productos Biológicos/efectos adversosRESUMEN
BACKGROUND: Gastrointestinal tuberculosis (TB) is a rare manifestation in low TB-incidence countries such as Austria. It is usually seen in immunocompromised patients or in migrants being more susceptible for extrapulmonary disease manifestations. CASE DESCRIPTION: We report a very rare manifestation of severe gastrointestinal TB in a 49-year-old previously healthy man from Upper Austria. Endoscopy showed a large tumor mass obstructing about 2/3 of the lumen of the cecum. Positron emission tomography/computed tomography scan revealed not only a high metabolic activity in the tumor mass, but also active pulmonary lesions in both upper lung lobes. Bronchial secretion showed acid-fast bacilli in the microscopy and polymerase chain reaction was positive for M. tuberculosis complex. Phenotypic resistance testing showed no resistance for first-line anti-TB drugs. Treatment with isoniazid, rifampicin, pyrazinamide and ethambutol was initiated. Based on therapeutic drug monitoring, the standard treatment regime was adapted to rifampicin high dose. TB treatment was well tolerated and the patient achieved relapse-free cure one year after the end of treatment. CONCLUSION: Gastrointestinal involvement mimicking an intestinal tumor is a very rare TB manifestation in previously healthy Austrians. However, it should be kept in mind due to increasing migration from countries with higher rates of extrapulmonary TB and due to an increasing number of immunocompromised patients. TB telephone consultations can support medical professionals in the diagnosis and the management of complex TB patients. TB management is currently at a transitional stage from a programmatic to personalized management concept including therapeutic drug monitoring or biomarker-guided treatment duration to achieve relapse-free cure.
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Neoplasias Gastrointestinales , Mycobacterium tuberculosis , Austria , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Rifampin/uso terapéuticoRESUMEN
BACKGROUND: In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Simple clinical risk scores may improve the management of COVID-19 patients. Therefore, the aim of this pilot study was to evaluate the quick Sequential Organ Failure Assessment (qSOFA) score, which is well established for other diseases, as an early risk assessment tool predicting a severe course of COVID-19. METHODS: We retrospectively analyzed data from adult COVID-19 patients hospitalized between March and July 2020. A critical disease progress was defined as admission to intensive care unit (ICU) or death. RESULTS: Of 64 COVID-19 patients, 33% (21/64) had a critical disease progression from which 13 patients had to be transferred to ICU. The COVID-19-associated mortality rate was 20%, increasing to 39% after ICU admission. All patients without a critical progress had a qSOFA scoreâ¯≤ 1 at admission. Patients with a critical progress had in only 14% (3/21) and in 20% (3/15) of cases a qSOFA scoreâ¯≥ 2 at admission (pâ¯= 0.023) or when measured directly before critical progression, respectively, while 95% (20/21) of patients with critical progress had an impairment oxygen saturation (SO2) at admission time requiring oxygen supplementation. CONCLUSION: A low qSOFA score cannot be used to assume short-term stable or noncritical disease status in COVID-19.
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COVID-19 , Sepsis , Adulto , COVID-19/diagnóstico , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Puntuaciones en la Disfunción de Órganos , Proyectos Piloto , Pronóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany.
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Infecciones por VIH , Tuberculosis Latente , Tuberculosis , Adulto , Humanos , Antituberculosos/uso terapéutico , Tuberculosis/diagnóstico , Tuberculosis/prevención & control , AlemaniaRESUMEN
BACKGROUND: The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB. METHODS: Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points. RESULTS: 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0â days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0â days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0â days, 23.4%; p=0.001). CONCLUSION: Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
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Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Adulto , Antituberculosos/uso terapéutico , Duración de la Terapia , Humanos , Transcriptoma , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
The clinical relevance of newly described nontuberculous mycobacteria is often unclear. We report a case of pulmonary infection caused by Mycobacterium hassiacum in an immunocompetent patient in Austria who had chronic obstructive pulmonary disease. Antimicrobial drug susceptibility testing showed low MICs for macrolides, aminoglycosides, fluoroquinolones, tetracyclines, imipenem, and linezolid.
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Enfermedades Pulmonares , Mycobacteriaceae , Infecciones por Mycobacterium no Tuberculosas , Austria , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/microbiología , Pruebas de Sensibilidad Microbiana , Mycobacteriaceae/efectos de los fármacos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológicoRESUMEN
Chronic pulmonary aspergillosis (CPA) is an uncommon, slowly destructive pulmonary disease characterized by progressive cavitation, fibrosis, and pleural thickening. CPA is usually seen in immunocompetent individuals with underlying respiratory disorders. Estimates suggest that up to 3 million people are affected worldwide causing high rates of morbidity and mortality. Pulmonary tuberculosis (TB) seems to be the most relevant driver for the global burden of CPA with estimates suggesting about 1.2 million patients with CPA as a sequel to TB. Diagnosis of CPA is often challenging and delayed and should be based upon a combination of characteristics. The first guidelines for the diagnosis and management of CPA were published in 2016 jointly by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS), and the European Confederation of Medical Mycology (ECMM). CPA continues to receive significant public attention, which resulted in almost 150 newly published papers during 2017. The aim of this mini-review is to highlight the most important published papers from January 2017 to April 2018 to provide an update on current developments in the field of CPA.
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Manejo de la Enfermedad , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Enfermedad Crónica , Salud Global , Humanos , Guías de Práctica Clínica como Asunto , Prevalencia , Aspergilosis Pulmonar/epidemiología , Aspergilosis Pulmonar/mortalidad , Tuberculosis Pulmonar/complicacionesRESUMEN
Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.
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Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/patología , Enfermedad Crónica , Países en Desarrollo , Humanos , Guías de Práctica Clínica como Asunto , Aspergilosis Pulmonar/microbiología , Factores SocioeconómicosRESUMEN
Chronic pulmonary aspergillosis (CPA) is a severe fungal infection with a high morbidity and mortality, and is usually seen in immunocompetent patients with respiratory disorders. Clinical presentation is nonspecific and often overlaps with the symptoms and the radiological pattern caused by the underlying disease. Clinical management of CPA is further hampered by limited information about the epidemiology, disease dynamics, sensitivity and specificity of different mycological tests, mechanisms of antifungal resistance, efficient treatment and management strategies. In order to contribute to a better understanding and to improve CPA patient management and outcome, we established the Chronic Pulmonary Aspergillosis Network (CPAnet), a self-organized multinational research collaboration. Key research priorities, defined by using a modified Delphi process, include the establishment of a multinational web-based registry, the validation of different diagnostic tests, the establishment of a culture collection from samples of patients with proven CPA and the establishment of a consensus on a treatment outcome definition.
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Investigación Biomédica/organización & administración , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Investigación , Enfermedad Crónica , Humanos , Enfermedades Desatendidas/epidemiología , Aspergilosis Pulmonar/epidemiologíaRESUMEN
The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-ß-D-glucan is recommended. Trimeth-oprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.