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Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260 BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3 months, increasing to 17.4% within 6 months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6 months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.
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Anticuerpos Monoclonales , Infección Irruptiva , COVID-19 , Profilaxis Pre-Exposición , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Estudios Retrospectivos , Receptores de Trasplantes , PulmónRESUMEN
BACKGROUND: Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin. OBJECTIVES: We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype. PATIENTS: We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations. RESULTS: These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction. CONCLUSIONS: CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.
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Inductores del Citocromo P-450 CYP3A , Nitrilos , Farmacogenética , Piridinas , Triazoles , Alelos , Citocromo P-450 CYP3A/genética , Inductores del Citocromo P-450 CYP3A/farmacocinética , Inductores del Citocromo P-450 CYP3A/uso terapéutico , Genotipo , Humanos , Nitrilos/farmacocinética , Nitrilos/uso terapéutico , Piridinas/farmacocinética , Piridinas/uso terapéutico , Rifampin , Triazoles/farmacocinética , Triazoles/uso terapéuticoRESUMEN
Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome.
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COVID-19/epidemiología , Trasplante de Pulmón/métodos , Insuficiencia Respiratoria/cirugía , SARS-CoV-2 , Receptores de Trasplantes , Adulto , Anciano , Bélgica/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Insuficiencia Respiratoria/epidemiología , Adulto JovenRESUMEN
A lung transplant recipient was diagnosed with penicilliosis due to Talaromyces marneffei, a fungus endemic in South-East Asia, which was acquired by donor transmission. This first case of Talaromyces marneffei-transmission by transplantation underscores that current globalisation of travelling necessitates increased vigilance for transmission of unusual pathogens in organ recipients.
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Trasplante de Pulmón/efectos adversos , Pulmón/microbiología , Micosis/microbiología , Micosis/transmisión , Talaromyces/aislamiento & purificación , Antifúngicos/uso terapéutico , Asia Sudoriental , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Tomografía Computarizada por Rayos X , ViajeRESUMEN
Introduction: Cystic fibrosis transmembrane regulator (CFTR) modulator therapies improve respiratory function and glycaemic control in patients with cystic fibrosis (CF). The direct effect of CFTR modulator therapies on pancreatic function in patients without preexisting diabetes remains unclear. Case Presentation. An 18-year-old female with CF caused by F508del/F508del mutation, who had no diabetes, developed postprandial hypoglycaemias 6 months after initiation of elexacaftor, tezacaftor, and ivacaftor combination therapy (ETI). Symptoms were persisted after brief discontinuation of ETI, but her symptoms and time-in-hypoglycaemia had improved remarkably by avoiding high glycaemic index-foods. Discussion. This case of hypoglycaemia associated with CFTR modulator therapy in a patient without preexisting diabetes suggests that CFTR modulator therapy has the potential to directly affect glucose homeostasis. There might be an improvement in insulin secretion as well as a reduction in systemic insulin resistance. Conclusion: Treatment of CF patients without diabetes with CFTR modulator therapies can cause recurrent hypoglycaemic episodes which resolve with dietary measures.
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Background: Long-term outcome data of coronavirus disease 2019 (COVID-19) survivors are needed to understand their recovery trajectory and additional care needs. Methods: A prospective observational multicentre cohort study was carried out of adults hospitalised with COVID-19 from March through May 2020. Workup at 3 and 12â months following admission consisted of clinical review, pulmonary function testing, 6-min walk distance (6MWD), muscle strength, chest computed tomography (CT) and quality of life questionnaires. We evaluated factors correlating with recovery by linear mixed effects modelling. Results: Of 695 patients admitted, 299 and 226 returned at 3 and 12â months, respectively (median age 59â years, 69% male, 31% severe disease). About half and a third of the patients reported fatigue, dyspnoea and/or cognitive impairment at 3 and 12â months, respectively. Reduced 6MWD and quadriceps strength were present in 20% and 60% at 3â months versus 7% and 30% at 12â months. A high anxiety score and body mass index correlated with poor functional recovery. At 3â months, diffusing capacity for carbon monoxide (D LCO) and total lung capacity were below the lower limit of normal in 35% and 18%, decreasing to 21% and 16% at 12â months; predictors of poor D LCO recovery were female sex, pre-existing lung disease, smoking and disease severity. Chest CT improved over time; 10% presented non-progressive fibrotic changes at 1â year. Conclusion: Many COVID-19 survivors, especially those with severe disease, experienced limitations at 3â months. At 1â year, the majority showed improvement to almost complete recovery. To identify additional care or rehabilitation needs, we recommend a timely multidisciplinary follow-up visit following COVID-19 admission.
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This article analyzes patterns of consumption of fluoroquinolones and documents the in vitro resistances of Streptococcus pneumoniae isolates to fluoroquinolones in the ambulatory care setting in Belgium over time. The volume of fluoroquinolone consumption has fallen consistently since 2003. Fluoroquinolones were used primarily for their registered indications (i.e., urinary tract infections and lower respiratory tract infections). The MIC distributions of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004 to 2009, and the level of resistance to moxifloxacin and levofloxacin was low (≤1%).
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Antibacterianos/farmacología , Compuestos Aza/farmacología , Levofloxacino , Ofloxacino/farmacología , Quinolinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Farmacorresistencia Bacteriana , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , MoxifloxacinoRESUMEN
OBJECTIVES: Pulmonary lymphomatoid granulomatosis (PLG) is a rare angiocentric and angiodestructive EBV-associated lymphoproliferative disorder which almost always affects the lungs. PLG is more commonly diagnosed in patients with immunodeficiency and is associated with Epstein-Barr virus (EBV). 'Drug induced PLG' or 'iatrogenic immunodeficiency-associated lymphoproliferative disorder' is a special form of PLG described in patient with inflammatory bowel diseases treated with Azathioprine. METHODS: We report a case of drug-induced PLG in a 68-year-old patient with Crohn's disease presenting with pain at the right hemithorax, fatigue and shortness of breath with a pulmonary mass. RESULTS: Although initial diagnostic findings were misleading, an open lung biopsy eventually led to the diagnosis of drug-induced PLG. CONCLUSION: The diagnosis of PLG is challenging because the disease is rare and the histological features can be very subtle. Correct diagnosis relies on histopathology and immunohistochemical staining and EBV RNA in situ hybridization with sampling of large and different amounts of pathologic tissue in the hands of expert pathologists. In drug-induced PLG specifically, withdrawal of the immunosuppressive agent can lead to disease regression.
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Azatioprina/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Granulomatosis Linfomatoide/inducido químicamente , Anciano , Biopsia , Broncoscopía , Dolor en el Pecho , Disnea , Endosonografía , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Granulomatosis Linfomatoide/inmunología , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
PURPOSE OF REVIEW: This review summarizes recent developments in the diagnosis and treatment of fungal pneumonia, with an emphasis on invasive pulmonary aspergillosis. RECENT FINDINGS: Improvements in nonculture-based fungal diagnostics, early implementation of pulmonary high resolution, or spiral computed tomography scanning and a recent expansion of the antifungal armamentarium have greatly improved the outcome of immunocompromised patients with invasive aspergillosis. However, the field is changing: new pathogens (such as Zygomycetes) are emerging, and novel risk groups (ICU patients in particular) are being identified. SUMMARY: Galactomannan antigen detection is a valuable tool for evaluating patients at risk for invasive aspergillosis (as a screening assay on serum samples from neutropenic patients or as a confirmatory assay on bronchoalveolar lavage fluid samples, in general), but should be used in conjunction with modern imaging techniques. beta-D-Glucan and PCR assays are still investigational. Voriconazole is the drug of choice for invasive aspergillosis, whereas liposomal amphotericin B at 3 mg/kg per day is the preferred alternative in case of contraindication, drug-related side-effects, or intolerance. Whenever possible, optimal antifungal therapy should be complemented by surgical debridement of necrotic tissue. The added value of combination therapy is still unproven. Therapeutic drug monitoring of mold-active azoles should be implemented in order to minimize toxicity and maximize efficacy. Lipid-based formulations of amphotericin B, and to a lesser extent voriconazole, are the drugs of choice for non-Aspergillus related fungal pneumonia. Although active in prophylaxis, the efficacy of posaconazole in confirmed infections remains controversial.
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Micosis/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Hongos/aislamiento & purificación , Galactosa/análogos & derivados , Humanos , Mananos/sangre , Micosis/diagnóstico , Neumonía/diagnóstico , Neumonía/microbiología , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Pirimidinas/uso terapéutico , Radiografía Torácica/métodos , Triazoles/uso terapéutico , VoriconazolRESUMEN
There is growing awareness of the need for advance care planning in patients with chronic obstructive pulmonary disease (COPD). However, do-not-resuscitate (DNR) order implementation remains a challenge in clinical practice. We retrospectively analysed an observational cohort of 569 COPD patients with 2.5-8â years of follow-up in secondary care, to evaluate potential determinants and the prognostic significance of DNR order implementation and specification. 345 patients (61%) had no DNR order, of whom 27% died during a median (interquartile range (IQR)) follow-up of 1935 (1290-2448)â days. 194 (39%) patients had a DNR order, of whom 17 had the order at baseline and 82% died (median (IQR) follow-up 528 (137-901) days), while 177 received an order during follow-up and 76% died (median (IQR) follow-up 1322 (721-2018) days). 88% of DNR orders were implemented during hospitalisation. 58% of the patients with a DNR order died within the first year after admission; of them, 66% died in the hospital. Age, forced expiratory volume in 1 s, chronic oxygen dependency and previous mechanical ventilation were significantly and independently associated with DNR order implementation. DNR order specification was significantly associated with increased mortality, even after adjustment for age and disease severity. These findings identify DNR orders as independent determinants of mortality, mainly implemented just before death.
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Clinical image of an asymmetrical mediastinal widening due to tuberculosis of mediastinal lymph nodes, without evidence of pulmonary tuberculosis. Image at first presentation and after successful treatment, showing normalization of the mediastinum.
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Enfermedades del Mediastino , Mediastino , Tuberculosis Pulmonar , Adulto , Antituberculosos/uso terapéutico , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Mediastino/diagnóstico por imagen , Mediastino/patologíaRESUMEN
We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. We discuss current screening methods and their limitations, the approach after positive screening and the timing to resume anti-TNFα treatment after TB infection. We shortly mention the immune reconstitution inflammatory syndrome (IRIS), described in a few cases after the stop of anti-TNFalpha while treating the tuberculosis infection. We conclude with some remaining questions concerning tuberculosis in IBD patients.
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Anticuerpos Monoclonales/efectos adversos , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Tuberculosis Pulmonar/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Reacciones Falso Negativas , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Tuberculosis Pulmonar/inducido químicamente , Tuberculosis Pulmonar/diagnósticoRESUMEN
BACKGROUND: Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms. METHODS: A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words 'cough' and 'gabapentin' in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire. RESULTS: We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms. Responders had a higher pre-treatment cough severity score (p=0.02) and were more likely to have a history of pre-cough airway infection (p=0.04). Current cough severity score negatively correlated with the Leicester Cough Questionnaire scores (p=0.05). CONCLUSION: Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection.
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BACKGROUND: Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation. METHODS: In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection. RESULTS: Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] µg/mL vs 14.45 [7.11-27.88] µg/mL, P < .05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV(1) % predicted [r = -0.53, P < .01], FVC% [r = -0.59, P < .01]) as well as with number of days of antibiotic IV treatment (r = 0.58, P < .01). CONCLUSIONS: BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.