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We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB).
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Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Mycobacterium tuberculosis/genética , Testes de Sensibilidade MicrobianaRESUMO
Mycoplasma hominis and Ureaplasma species infections in the post-transplant setting are believed to be donor-derived and can be associated with poor outcomes. Difficulty in culturing and identifying these organisms is a significant barrier to diagnosis and early intervention. Tetracyclines, macrolides and fluoroquinolones are the mainstay treatments to cure these infections; however, there are increasing reports of antibiotic resistance. In this case series, we report our single-centre experience with M. hominis and U. urealyticum infection after lung transplantation (9 recipients, all men, mean age 56 years). Delayed diagnosis was common. Young donor age (mean age 23 yrs) and high-risk donor social history (67%) were repeatedly noted in these cases, and all infections were associated with significant morbidity (anastomosis and sternal wound infection, empyema, mediastinitis, pericarditis). Two patients died; with one directly related to Ureaplasma urealyticum infection. In conclusion post lung transplant M. hominis, and U. urealyticum infections are challenging and carry high morbidity. More prospective studies are required to assess the true prevalence, full spectrum of complications and utility of molecular diagnostics to aid early diagnosis and identify antibiotic susceptibility of Mycoplasma and Ureaplasma infections in the post-lung transplant setting.
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Mediastinite , Infecções por Ureaplasma , Masculino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Ureaplasma urealyticum , Mycoplasma hominis , Infecções por Ureaplasma/diagnóstico , Infecções por Ureaplasma/tratamento farmacológico , Infecções por Ureaplasma/epidemiologia , Ureaplasma , Antibacterianos/uso terapêuticoRESUMO
Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.
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Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Humanos , Fibrose Cística/tratamento farmacológico , Micobactérias não Tuberculosas , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologiaRESUMO
The remarkable ascent of entrepreneurship witnessed as a scientific field over the last 4 decades has been made possible by entrepreneurship's ability to absorb theories, paradigms, and methods from other fields such as economics, psychology, sociology, geography, and even biology. The respectability of entrepreneurship as an academic discipline is now evidenced by many other fields starting to borrow from the entrepreneurship view. In the present paper, seven examples are given from this "pay back" development. These examples were first presented during a seminar at the Erasmus Entrepreneurship Event called what has the entrepreneurship view to offer to other academic fields? This article elaborates on the core ideas of these presentations and focuses on the overarching question of how entrepreneurship research impacts the development of other academic fields. We found that entrepreneurship research questions the core assumptions of other academic fields and provides new insights into the antecedents, mechanisms, and consequences of their respective core phenomena. Moreover, entrepreneurship research helps to legitimize other academic fields both practically and academically.
Entrepreneurship research questions the core assumptions of other academic fields and legitimizes them both practically and academically. Since the 1980s, entrepreneurship research has seen tremendous growth and development, establishing itself as an academic field. Entrepreneurship is also taught extensively in leading business schools around the world. Indeed, few business schools do not address entrepreneurship in their curriculum. This represents a sea change: although entrepreneurs and new ventures had a remarkable impact on society, academia barely noticed it in the 1980s. Simply put: economics and business students rarely, if ever, encountered any mention of entrepreneurship during their studies. While entrepreneurship research has now developed its own methodological toolbox, it has extensively borrowed perspectives, theories, and methods from other fields. In the 2020s, we now find that entrepreneurship scholars are sharing its toolbox with other academic fields, questioning the core assumptions of other academic fields and providing new insights into the antecedents, mechanisms, and consequences of their respective core phenomena. Moreover, entrepreneurship research helps to legitimize other academic fields both practically and academically. Hence, entrepreneurship research now plays not just an important role in entrepreneurship education, practice, and policy but also throughout many other research fields.
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BACKGROUND: During the 2020 COVID-19 pandemic, governments imposed numerous regulations to protect public health, particularly the (mandatory) use of face masks. However, the appropriateness and effectiveness of face mask regulations have been widely discussed, as is apparent from the divergent measures taken across and within countries over time, including mandating, recommending, and discouraging their use. In this study, we analyse how country-level policy stringency and individual-level predictors associate with face mask use during the early stages of the global COVID-19 pandemic. METHOD: First, we study how (self and other-related) risk perception, (direct and indirect) experience with COVID-19, attitude towards government and policy stringency shape face mask use. Second, we study whether there is an interaction between policy stringency and the individual-level variables. We conduct multilevel analyses exploiting variation in face mask regulations across countries and using data from approximately 7000 students collected in the beginning of the pandemic (weeks 17 through 19, 2020). RESULTS: We show that policy stringency is strongly positively associated with face mask use. We find a positive association between self-related risk perception and mask use, but no relationship of mask use with experience with COVID-19 and attitudes towards government. However, in the interaction analyses, we find that government trust and perceived clarity of communication moderate the link between stringency and mask use, with positive government perceptions relating to higher use in countries with regulations and to lower use in countries without regulations. CONCLUSIONS: We highlight that those countries that aim for widespread use of face masks should set strict measures, stress self-related risks of COVID-19, and use clear communication.
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COVID-19 , Máscaras , Governo , Humanos , Pandemias , Percepção , Políticas , SARS-CoV-2RESUMO
OBJECTIVE: Patients with serious mental illness (SMI) are at increased risk of obstructive sleep apnoea (OSA). Despite this, OSA is frequently under-recognised in the psychiatric population. This study describes the results of OSA screening in SMI patients. METHOD: Patients with SMI attending a metropolitan mental health clinic were screened for OSA using the OSA50, STOP-BANG Questionnaire (SBQ), Epworth Sleep Score (ESS) and the Pittsburgh Sleep Quality Index (PSQI). They were then offered diagnostic sleep testing via ResMed ApneaLinkTM and polysomnography. RESULTS: Of the 65 patients recruited, 65% had a primary diagnosis of schizophrenia or schizoaffective disorder, 85% were on antipsychotic medications and the majority were obese. Approximately 50% of patients reported poor sleep quality via the PSQI, in contrast to 12% with elevated daytime sleepiness via the ESS. 46% of our cohort were at risk of OSA due to an elevated OSA50 or SBQ. Of the five patients who agreed to proceed to diagnostic sleep testing, three were diagnosed with OSA. CONCLUSION: A high proportion of patients with psychiatric illness are at risk of sleep-disordered breathing. Sleep dissatisfaction is high. The low uptake of sleep investigation requires improved patient engagement to improve OSA diagnosis in this high-risk group.
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Antipsicóticos , Transtornos Mentais , Apneia Obstrutiva do Sono , Humanos , Programas de Rastreamento , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
During the 2020 COVID-19 pandemic, governments set recommendations and restrictions that have given rise to new situations that require residents to deliberate and respond nonautomatically. For highly impulsive individuals, dealing with these situations may be harder, as they tend to deliberate less about the consequences of their behaviors. In this study, we investigate the relationship between impulsivity and delay discounting on the one hand and compliance with COVID-19 restrictions on the other hand. We distinguish between compliance with social distancing measures and compliance with hygiene measures. Regression analyses of an international sample of 6759 students from seven European countries reveal that the self-reported personality construct of impulsivity is negatively related to both types of compliance behavior. However, and unexpectedly, we also find a weak positive association between the discount rate-as measured by a behavioral task-and compliance. Our study highlights the importance of individual differences in impulsivity in regard to compliance with public health measures during a pandemic.
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BACKGROUND: Patients with serious mental illness (SMI) have an increased risk of sudden death. Higher rates of signal-averaged electrocardiogram (SAECG) abnormal late potentials (LP), which may be a predictor of sudden death risk, have been shown in patients with schizophrenia. We aimed to assess the prevalence and predictors of electrocardiograph (ECG) and SAECG abnormalities in a mixed SMI population. METHODS: Consecutive consenting inpatients with SMI had 12-lead ECG and SAECG recorded in addition to demographics, diagnoses and medications. Standard criteria for abnormal SAECG were applied. Multivariate regression analysis was performed to determine predictors of SAECG abnormalities including diagnoses, body mass index, ECG parameters, psychotropic medication use, and medications associated with Long QT or Brugada syndromes. RESULTS: Eighty (80) patients, 49% male, mean age 39±17 years were included. SAECG criteria abnormality for 1, 2 or 3 criteria were seen in 19, 3 and 5 cases (34% in total) respectively. Early repolarisation pattern was seen in 19% of patients. SAECG abnormality was associated with male gender (OR 7.3; 95% CI 2.3-23.4), and schizophrenia/schizoaffective disorder diagnosis (OR 7.4; 95% CI 1.9-29.0), but not with medication type or dose. CONCLUSIONS: In the mixed SMI population studied, there was a high rate of SAECG-detected late potentials (34%) and early repolarisation pattern (19%). Schizophrenia/schizoaffective disorder diagnosis was the strongest multivariate predictor identified. Further studies are needed to define the mechanism and significance of these cardiac abnormalities in SMI patients.
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Arritmias Cardíacas/etiologia , Morte Súbita Cardíaca/etiologia , Eletrocardiografia/métodos , Transtornos Mentais/complicações , Medição de Risco/métodos , Adulto , Arritmias Cardíacas/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Valor Preditivo dos Testes , Queensland/epidemiologia , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: People with severe mental illness (SMI) have a lower life expectancy due in part to a higher prevalence of cardiac and metabolic disease. Less is known of the prevalence of respiratory disease in this group. AIMS: This cross-sectional, observational study aimed to assess the prevalence of symptoms associated with respiratory disease in patients admitted to an inpatient mental health unit. METHODS: A convenience sample of 82 inpatients had a structured interview and questionnaire completed. The questionnaire included self-reported diagnoses of common diseases and screening questions designed to detect respiratory disease and sleep disordered breathing. Targeted spirometry was performed on the basis of symptoms and smoking status. RESULTS: Patients reported high rates of respiratory symptoms, including wheezing (38%) and dyspnoea (44%); 52% of patients reported daily tobacco use. Productive cough was significantly associated with tobacco use (P < 0.005). Ten patients (18%) had spirometry consistent with chronic obstructive pulmonary disease (COPD) of whom six did not have a formal diagnosis of COPD previously. CONCLUSIONS: People with SMI have high rates of respiratory symptoms with a high prevalence of COPD on spirometry. Half of the COPD cases were not previously diagnosed, suggesting a hidden burden of respiratory disease in patients with SMI.
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Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Saúde Mental/tendências , Transtornos Respiratórios/diagnóstico , Transtornos Respiratórios/epidemiologia , Centros de Atenção Terciária/tendências , Adolescente , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/tendências , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/epidemiologia , Fumar/tendências , Espirometria/tendências , Adulto JovemRESUMO
Importance: In observational studies, increased water intake is associated with better kidney function. Objective: To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. Design, Setting, and Participants: The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. Interventions: Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. Main Outcomes and Measures: The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). Results: Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22). Conclusions and Relevance: Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: clinicaltrials.gov Identifier: NCT01766687.
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Ingestão de Líquidos , Tutoria , Insuficiência Renal Crônica/terapia , Água/administração & dosagem , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Educação de Pacientes como Assunto , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Urina/químicaRESUMO
To predict the market dynamics of various zero-emission vehicle (ZEV) technologies, this study introduces a dynamic discrete vehicle choice model (VCM) that investigates the probabilities associated with 14 decision factors, applying these to the purchase of ZEVs from 2020 to 2040. Market share and penetration results are presented under eight scenarios, that vary by vehicle costs infrastructure development and incentive strategies. The findings suggest that in the early years, incentives alone may not generate significant market penetration of ZEVs before the infrastructure meets the basic convenience for daily use, especially for fuel cell vehicles (FCVs). However, in later years, incentives play a more important role in the market penetration of ZEVs under well-defined infrastructure networks. By 2040, battery electric vehicles (BEVs) are projected to dominate the market in California. Plug-in hybrid electric vehicles (PHEVs) and FCVs may experience a decline in market share due to improved charging convenience, which benefits the market penetration of BEVs. However, fuel cell plug-in hybrid electric vehicles (FC-PHEVs) could still be beneficial if accessible models are available, considering the limited availability of hydrogen refueling stations. The goal set by the California Air Resources Board (CARB) is achievable, but it requires a sustained combination of measures; no single effort can achieve it. These measures include technological improvements to reduce the cost of ZEVs, a wider range of models available for consumers to choose from based on their desired performance, the establishment of infrastructure (battery chargers and hydrogen dispensers), and attractive incentives aimed at promoting ZEV adoption. The proposed methodology can be adapted for other regions in the United States and globally by carefully examining the inputs for each decision factor at the desired scale.
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Mycobacterium thermoresistibile is a thermotolerant nontuberculous mycobacterium which can rarely result in human infection. Although immunosuppression has been identified as a risk factor for infection, it is possible that mycobacterial laboratories may have previously under-recognized M. thermoresistibile as standard mycobacterial incubation temperatures are suboptimal for culture of this organism. Here, we present a case of severe M. thermoresistibile pneumonia associated with achalasia requiring life support in the intensive care unit. We speculated that the interplay between specific host and environmental risk factors contributed to acquisition of infection. Infection with this fastidious organism required prolonged treatment with multiple antimicrobials and adjunctive therapeutic drug monitoring which led to clinical cure despite residual lung injury. We also reviewed literature documenting cases of human infection with M. thermoresistibile. The diagnosis of M. thermoresistibile requires a high degree of clinical suspicion considering its association with immunosuppressive conditions, postulated environmental inoculation and eponymous culture growth characteristics.
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Rationale: Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection.Objectives: This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection (Mycobacterium avium complex [MAC] and M. abscessus [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability.Methods: Thirty-two adult patients with refractory NTM infection (MAC, n = 24; MABS, n = 8) were recruited into two cohorts: those with (n = 16) and without (n = 16) ongoing GBT. Nebulized molgramostim 300 µg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period.Results: Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported.Conclusions: In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).
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Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Adulto , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Projetos Piloto , Qualidade de Vida , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Complexo Mycobacterium avium , Micobactérias não Tuberculosas , Proteínas RecombinantesRESUMO
Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.
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BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA. STUDY QUESTION: What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients? STUDY DESIGN AND METHODS: Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models. RESULTS: We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2% (331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95% CI, 1.7-13.8; I2 = 45%), harbored a hematogenous malignancy (OR, 2.5; 95% CI, 1.5-4.1; I2 = 0%), were immunocompromised (OR, 2.2; 95% CI, 1.6-3.1; I2 = 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95% CI, 1.4-4.3; I2 = 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95% CI, 1.8-3.8; I2 = 0%). INTERPRETATION: IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm. TRIAL REGISTRY: International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/.
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Influenza Humana , Aspergilose Pulmonar , Humanos , Estado Terminal/terapia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Prevalência , Aspergilose Pulmonar/complicações , Fatores de RiscoAssuntos
Técnicas de Diagnóstico do Sistema Respiratório/instrumentação , Esquizofrenia/complicações , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Estudos de Viabilidade , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Apneia Obstrutiva do Sono/complicações , Adulto JovemAssuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Miliar/diagnóstico por imagem , Tuberculose Miliar/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico , Controle de Doenças Transmissíveis/organização & administração , Busca de Comunicante , Quimioterapia Combinada , Família , Humanos , Incidência , Lactente , Masculino , Prognóstico , Queensland , Radiografia Torácica/métodos , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodosRESUMO
In the treatment of nontuberculous mycobacteria (NTM) lung disease, clinicians must consider potential toxicities that may occur as a result of prolonged exposure to a multidrug antibiotic regimen. Frequent clinical and microbiological monitoring is required to assess response and guide treatment duration. This article summarizes toxicity profiles of the antibiotics that are most frequently prescribed for the treatment of NTM lung disease. The role of therapeutic drug monitoring during use of amikacin and linezolid is discussed. The available evidence to guide frequency and extent of medication monitoring during NTM treatment is provided.
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Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pulmão , Antibacterianos/efeitos adversos , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologiaRESUMO
Mycobacterium marinum is a ubiquitous water-borne non-tuberculous mycobacterial (NTM) pathogen. In humans, M. marinum infections are acquired through direct inoculation of skin wounds and are almost exclusively localized to skin and soft tissues. Pulmonary infection with M. marinum is extremely rare, and to our knowledge, invasive endobronchial disease has not been reported. Here, we present a case of a 71-year-old immunocompetent male surfer with invasive endotracheal M. marinum granulomatous disease. The patient was successfully cured with a regimen of azithromycin 250 mg daily, ethambutol 900 mg (15 mg/kg) daily and rifampicin 600 mg daily for 12 months following culture conversion. This case highlights several important concepts: Firstly, M. marinum infection, including invasive endobronchial infection, should be considered a rare cause of NTM pulmonary disease. Secondly, endotracheal infection can be successfully eradicated with this selected therapeutic regimen. Finally, the absence of M. marinum skin or soft-tissue infection in this patient, raises the possibility that human disease might also be acquired via inhalation of M. marinum contaminated water in rare circumstances.
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OBJECTIVES: Mycobacterium abscessus is an emerging infection in people living with lung diseases, including cystic fibrosis (CF) and bronchiectasis, and it has limited treatment options and low cure rates. The off-label use of novel antibiotics developed for other bacterial pathogens offers potential new therapeutic options. We aimed to describe the in vitro activity of imipenem, imipenem-relebactam and tedizolid against comparator antibiotics in M. abscessus isolates from Australian patients with and without CF. METHODS: We performed susceptibility testing for imipenem-relebactam, tedizolid and comparator antibiotics by Clinical and Laboratory Standards Institute (CLSI) criteria against 102 clinical M. abscessus isolates, including 46 from people with CF. RESULTS: In this study, the minimum inhibitory concentration (MICs) of imipenem-relebactam was one-fold dilution less than of imipenem alone. The MIC50 and MIC90 of imipenem-relebactam were 8 and 16 mg/L, respectively, whereas for imipenem they were 16 and 32 mg/L. Tedizolid had an MIC50 and MIC90 of 2 and 4 mg/L, respectively. Forty non-CF isolates had linezolid susceptibility performed, with MIC50 and MIC90 values of 16 and 32 mg/L, respectively, measured. CONCLUSIONS: This study shows lower MICs for imipenem-relebactam and tedizolid compared to other more commonly used antibiotics and supports their consideration in clinical trials for M. abscessus treatment.