Caracterización y resultados del uso de voriconazol nebulizado en un entorno real: un estudio observacional unicéntrico / Characterization and real-live results of nebulized voriconazole: A single-center observational study

Objetivo la administración de voriconazol nebulizado implica ventajas, incluyendo la optimización de la penetración pulmonar y la reducción de los efectos adversos e interacciones; sin embargo, la evidencia sobre su utilización es escasa y no existen presentaciones comerciales específicas para nebulización. Nuestro objetivo es caracterizar las soluciones de voriconazol elaboradas para nebulización y describir su uso en nuestro centro. Método estudio observacional retrospectivo incluyendo pacientes que reciben voriconazol nebulizado para el tratamiento de enfermedades pulmonares (infecciones fúngicas o colonizaciones). La solución de voriconazol se preparó a partir de los viales comerciales para la administración intravenosa. Resultados el pH y la osmolaridad de las soluciones de voriconazol fueron adecuados para su nebulización. Se incluyeron 10 pacientes, 9 adultos y un niño. La dosis fue de 40 mg en los adultos y 10 mg en el paciente pediátrico, diluido a 10 mg/ml, administrados cada 12-24 horas. La duración mediana del tratamiento fue de 139 (rango: 26-911) días. No se reportaron efectos adversos y no se detectó voriconazol en plasma cuando se administró únicamente vía nebulizada. Conclusiones la nebulización de voriconazol es bien tolerada y no se absorbe hacia la circulación sistémica. Son necesarios más estudios de investigación para evaluar su eficacia (AU)

Objective Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. Method This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. Results The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. Conclusion Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy (AU)

Characterization and real-live results of nebulized voriconazole: A single-center observational study.

OBJECTIVE: Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. METHOD: This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. RESULTS: The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, 9 adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 h. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. CONCLUSION: Voriconazole nebulization is well-tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Characterization and real-live results of nebulized voriconazole: A single-center observational study. / [Artículo traducido] Caracterización y resultados del uso de voriconazol nebulizado en un entorno real: un estudio observacional unicéntrico.

OBJECTIVE: Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. METHOD: This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. RESULTS: The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. CONCLUSION: Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Decoding the Guidelines of Invasive Pulmonary Aspergillosis in Critical Care Setting: Imaging Perspective.

Invasive pulmonary aspergillosis (IPA) is a common, life-threatening opportunistic fungal infection seen in susceptible individuals especially those admitted in critical care units. Multiple guidelines have been promulgated for the diagnosis of IPA, some of which are all inclusive, while others cater to specific patient groups. Microbiology forms the crux of the majority of the diagnostic tests/criteria; however, results take a considerable amount of time. Radiology can play an important role by bridging the gap to reach at an early diagnosis. Thus, the role of a radiologist cannot be overemphasized to recognize the typical and atypical imaging manifestations of invasive aspergillosis and aid in the swift management of these cases. This review decodes the terminology and various diagnostic criteria for IPA relevant to imaging studies. Further, the differences in imaging manifestations of IPA in neutropenic and non-neutropenic patients are also discussed.

Differential Proinflammatory Responses to Aspergillus fumigatus by Airway Epithelial Cells In Vitro Are Protease Dependent.

Aspergillus fumigatus is an important human respiratory mould pathogen. In addition to a barrier function, airway epithelium elicits a robust defence against inhaled A. fumigatus by initiating an immune response. The manner by which A. fumigatus initiates this response and the reasons for the immunological heterogeneity with different isolates are unclear. Both direct fungal cell wall-epithelial cell interaction and secretion of soluble proteases have been proposed as possible mechanisms. Our aim was to determine the contribution of fungal proteases to the induction of epithelial IL-6 and IL-8 in response to different A. fumigatus isolates. Airway epithelial cells were exposed to conidia from a low or high protease-producing strain of A. fumigatus, and IL-6 and IL-8 gene expression and protein production were quantified. The role of proteases in cytokine production was further determined using specific protease inhibitors. The proinflammatory cytokine response correlated with conidia germination and hyphal extension. IL-8 induction was significantly reduced in the presence of matrix metalloprotease or cysteine protease inhibitors. With a high protease-producing strain of A. fumigatus, IL-6 release was metalloprotease dependent. Dectin-1 antagonism also inhibited the production of both cytokines. In conclusion, A. fumigatus-secreted proteases mediate a proinflammatory response by airway epithelial cells in a strain-dependent manner.

Chronic pulmonary aspergillosis in a tertiary care centre in Spain: A retrospective, observational study.

The aim of this study was to describe the characteristics of patients with chronic pulmonary aspergillosis (CPA) in a tertiary care centre in Spain. Retrospective cohort study of all patients diagnosed with CPA between January 2010 and December 2015. The patients were identified through the Microbiology Registry. Demographic, clinical, laboratory, radiological, microbiological and clinical data were recorded. Patients were followed up for 12 months. Fifty-three patients were included; median age was 61.5 years. Forty-seven had a lung condition, 25 suffered from COPD, 19 an active malignancy, 10 had previous pulmonary tuberculosis and 9 lung interstitial disease. Twenty-eight patients presented with chronic cavitary pulmonary form (CCPA) and 20 with subacute invasive aspergillosis (SAIA). Species identified were A fumigatus (34), A niger (5), A terreus (4) and A flavus (3). All-cause 1-year mortality was 56%. Predictors of mortality were cancer history (OR, 9.5; 95% CI, 2.54-35.51; P < 0.01) and SAIA (OR, 5.49; 95% CI, 1.49-19.82; P < 0.01). Previous pulmonary tuberculosis, surgery for the treatment of CPA and CCPA were found to be associated with lower mortality (OR, 0.05; 95% CI, <0.01-0.47; P < 0.01; OR, 0.16; 95% CI, 0.03-0.88; P = 0.035 and OR 0.2, 95% CI, 0.01-0.67; P = 0.01, respectively). This is the first study providing an overview of the features of CPA in patients from Spain. CCPA was the most frequent form of CPA and A fumigatus the most frequently isolated species. Patients with cancer history and SAIA had a worse prognosis.

Analysis of factors implicated in the outcomes of patients with invasive pulmonary aspergillosis / 中华急诊医学杂志

Objective To investigate the factors implicated in the outcomes of patients with invasive pulmonary aspergillosis (IPA).Methods During a 5-year period,65 patients with IPA met the criteria set by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)in 2008 were retrospectively evaluated. The initial CT findings of eligible patients were reviewed by two senior radiologists who specialized in chest radiology.Patients were divided into the survivor (n =43 ) and non-survivor (n =22) groups according to their survival as long as 3 months after the diagnosis of IPA was made.An initial univariate analysis was used to screen variables that were related to prognosis,followed by a multivariate logistic regression analysis to examine these variables. Results Of the 65 IPA patients analyzed,23 (35％) had a proven diagnosis and 42 (65％) were probable ones.The univariate analysis showed that the rates of extra-pulmonary infection,uncontrolled underlying diseases and invasive mechanical ventilation were significantly different between the 3-month survival group and the non-survival group ( P ＜0.05,respectively),whereas chest CT findings,including air-space consolidation/massive consolidation,macronodules,infarct-like macronodules,halo signs, ground-glass opacities,small nodules,hypodense signs,cavities,crescent signs,small-airway findings,bronchial wall thickening/bronchiectasis,pleural effusion and hydro-pericardium, were not significantly different between the two groups (P ＞ O.05,respectively).Logistic regression analysis revealed that an uncontrolled underlying disease was the only independent predictor of 3-month mortality in patients with IPA (P =0.001,OR:O.024,95 ％ CI:O.003 ～0.223,B =- 3.714,SE =1.129,Wald =10.821 ). Conclusions An uncontrolled co-morbidity was the only independent predictor of mortality within 3 months in patients with IPA.The initial CT findings did not confer any informatioin of implication in predicting the outcomes of IPA patients.