Katerina Manika

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: A multicentre study

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents. 428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92–280) days and exposed to bedaquiline for 168 (86–180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively). Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30–60) days and 60 (33–90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related. Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions. Bedaquiline is safe and effective in treating MDR- and XDR-TB patients http://ow.ly/6MWK30adHkw

COPD Assessment Test: A Simple Tool to Evaluate Disease Severity and Response to Treatment

Abstract The COPD assessment test (CAT) is a short questionnaire designed to assess the impairment in health status of COPD patients. We aimed to determine the change of the CAT in COPD patients after 1 year of treatment and test the association between the score and clinical and lung function variables. Methods A cohort of 111 newly diagnosed COPD patients in primary care was evaluated at baseline and one year after the implementation of the recommended treatment according to the Global Initiative for the management of COPD (GOLD). Results Most of the patients (82%) were diagnosed with mild to moderate airflow limitation (mean FEV1 72 ± 21.5% predicted) and the CAT score increased in proportion with the GOLD stage of severity. The CAT significantly correlated with the number of exacerbations, visits to general practitioners and days of hospitalization both at the beginning and at 1 year follow-up. A strong negative correlation between the CAT score and FEV1 predicted was also observed. The CAT was responsive to the application of treatment with a significant improvement in the mean score (95% confidence interval) following 12 months of treatment by –2.4 (–2.9, –1.9) despite the small decline in lung function indices. The number of exacerbations in the preceding year and FEV1 were independent predictors of the CAT score in the general linear model. Conclusion The CAT questionnaire may serve as a simple, measurable tool complementary to spirometry in the assessment of severity and of response to treatment in unselected COPD patients in primary care.

Experimentation with inhaled bronchodilators and corticosteroids

BACKGROUND Inhaled bronchodilators and corticosteroids have been used for decades with different production systems. MATERIALS AND METHODS The following jet-nebulizers: (a) Invacare, (b) Sunmist, (c) Maxineb and ultrasound nebulizers: (a) GIMA, (b) OMRON and (c) EASY NEB II were used as production systems. The jet-nebulizers were used with different residual cups and volume filling, while the ultrasound nebulizers with different volume fillings and face mask versus inlet. RESULTS Inhalation and ultrasound process detect significant differences between the factors and interactions considered, but each technique follows a specific pattern of magnitude effect. Thus the inhaled mechanism ranks the factor effects in decreasing order: residual cup>drug>nebulizer>loading (2, 3, 4 ml) and also drug>residual cup>nebulizer (loading 8 ml). The ultrasound mechanism orders as follows: nebulizer>drug>loading. In fact, varying micro environmental conditions created during the performance of the devices in both processes alternate the magnitude of factor significance allowing for unique capacities. CONCLUSIONS PULMICORT, MAXINEB, design cup J and loading 6 ml are the best options for the inhaled process. Optimal combinations are provided by FLIXOTIDE and cup B and also by MAXINEB and cup J. The incorporation of large residual cups suggests one out of six drugs, the SUNMIST nebulizer and design D as the best choices. Ultrasound performance informs for other optimal conditions: ZYLOREN, MAXINEB, 4 ml load and MAXINEB×loading 4 ml.

Pulmonary rehabilitation in non-small cell lung cancer patients after completion of treatment.

ObjectivesThe functional status of patients with non-small cell lung cancer (NSCLC) is often limited not only by cancer itself, but also by the different types of treatment and by comorbidities [eg, chronic obstructive pulmonary disease (COPD), congestive heart failure]. The aim of this study was to investigate the utility of an inpatient multidisciplinary pulmonary rehabilitation (PR) program on pulmonary function and exercise capacity of patients with NSCLC after completion of their treatment. MethodsForty-seven patients with NSCLC underwent a PR program after completing cancer treatment. Pulmonary function tests, arterial blood gases, 6-minute walk test, and dyspnea severity before and after PR were retrospectively analyzed. ResultsAfter undergoing PR, patients exhibited significantly higher forced expiratory volume in the first second (mean increase, 110±240 mL; P=0.007), forced vital capacity (mean increase, 130±290 mL; P=0.001), and 6-minute walk test distance (mean increase, 41 m; P<0.001). A statistically significant improvement in the severity of dyspnea (mean decrease in the Modified Medical Research Council dyspnea scale: 0.26±0.61; P=0.007) was observed. We observed that improvement in pulmonary function and exercise capacity was similar among patients with and without COPD and among patients who underwent thoracic surgery or not. ConclusionsPatients with NSCLC who could accomplish PR program, after multidisciplinary treatment for the main disease, seem to benefit in terms of exercise capacity and pulmonary function. These benefits are independent of concurrent COPD and surgical treatment for lung cancer.

Pneumothorax in sarcoidosis

While sarcoidosis is a relatively common but often underdiagnosed disease, pneumothorax appears to be a rare clinical event observed mostly at the late stages of the disease course. The precise underlying mechanism of such complication is unclear and probably involves the formation of bullae due to bronchial obstruction and retraction-collapse of distracted lung tissue. Thoracoscopic bullectomy represent the preferred treatment option for recurrent pneumothoraces. The administration of corticosteroids for the treatment of pulmonary sarcoidosis may have a protecting effect for such recurrences, but remains a controversial issue.

Asthma Control Test Is Correlated to FEV1 and Nitric Oxide in Greek Asthmatic Patients: Influence of Treatment

Background. Asthma is a common chronic disease affecting patients’ health status and quality of life. Although recent guidelines focus on asthma control, asthma remains poorly controlled in many patients even under specialist care. Asthma Control Test™ (ACT) is a short, simple, patient-based tool that provides consistent assessment of asthma. Objective. The aim of this study was to estimate the relationship of ACT with objective measures of lung function and inflammation such as forced expiratory volume in 1st second (FEV1) and exhaled nitric oxide (FeNO) in outpatients admitted for initial diagnosis of asthma and at follow-up. Methods. One hundred and sixty (104 women and 56 men, mean age 39.7 ± 16.6 years) asthmatic patients with newly diagnosed asthma were included in the study. Patients completed the ACT questionnaire and underwent a detailed clinical examination, FeNO measurement, and prebronchodilator spirometry before (visit 1) and 4–12 weeks after initiation of treatment (visit 2). Results. At visit 1, the mean ACT score was 21.27 ± 3.74. According to ACT score, 37 patients (23.1%) were completely controlled, 85 patients (53.1%) were partly controlled, and 38 patients (23.8%) were uncontrolled. Patients with uncontrolled asthma had statistically higher FeNO values than patients with partly controlled (p = .038) and completely controlled asthma (p = .016). ACT score was found to have a positive correlation with prebronchodilator %FEV1 (r = 0.177, p = .025) and negative correlation with FeNO ( r = −0.211, p = .007). At visit 2, the mean ACT score was 23.00 ± 2.19. The change in ACT score between the two visits was significantly correlated to changes in FEV1 (r = 0.538, p < .001) and in FeNO (r = −0.466, p < .001). Patients treated with inhaled corticosteroids (ICSs) showed significant improvement in FEV1 and in ACT score and a decrease in FeNO compared with patients without ICS treatment. Conclusion. Although FEV1 remains the main objective parameter for evaluating asthma, ACT score was found to reflect lung function and inflammation in a Greek asthmatic population.

Efficacy and safety of erythromycin as sclerosing agent in patients with recurrent malignant pleural effusion.

Objectives:The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent. Methods:Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded. Results:The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics. Conclusions:This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions.

The Impact of Pulmonary Arterial Pressure on Exercise Capacity in Mild-to-Moderate Cystic Fibrosis: A Case Control Study

Background. Pulmonary hypertension (PH) is an often complication of severe cystic fibrosis (CF); however, data on the presence and impact of pulmonary vasculopathy in adult CF patients with milder disease, is very limited. Aim. To investigate, for the first time, the impact of systolic pulmonary arterial pressure (PASP) on maximal exercise capacity in adults with mild-to-moderate cystic fibrosis, without PH at rest. Methods. This is a Case Control study. Seventeen adults with mild-to-moderate CF, without PH at rest (cases) and 10 healthy, nonsmoking, age, and height matched controls were studied. All subjects underwent maximal cardiopulmonary exercise testing and echocardiography before and within 1 minute after stopping exercise. Results. Exercise ventilation parameters were similar in the two groups; however, cases, compared to controls, had higher postexercise PASP and decreased exercise capacity, established with lower peak work rate, peak O2 uptake, anaerobic threshold, and peak O2 pulse. Furthermore, the change in PASP values before and after exercise was strongly correlated to the parameters of exercise capacity among cases but not among controls. Conclusions. CF adults with mild-to-moderate disease should be screened for the presence of pulmonary vasculopathy, since the elevation of PASP during exercise might contribute to impaired exercise capacity.

Pharmacokinetics of moxifloxacin and high-dose levofloxacin in severe lower respiratory tract infections

This study evaluated the pharmacokinetics of intravenous moxifloxacin 400 mg once and levofloxacin 500 mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC(0-24)/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81 ± 1.03 and 0.59 ± 1.13 mg/L for moxifloxacin and 6.42 ± 1.08 and 0.79 ± 0.39 mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27 ± 1.24 and 22.66 ± 6.62 L/h; t1/2, 13.43 ± 5.12 and 6.75 ± 1.34 h; Vss, 163.03 ± 53.88 and 170.73 ± 39.59 L; and AUC(0-24), 39.38 ±5.28 and 47.06 ± 14.09 mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs ≤ 0.79 mg/L and Gram-negative bacteria with MICs ≤ 0.32 mg/L. These MIC thresholds for levofloxacin were 1.1 mg/L and 0.38 mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs ≥ 0.5 mg/L appears to be low.

Moxifloxacin in multidrug-resistant tuberculosis: is there any indication for therapeutic drug monitoring?

To the Editors: Fluoroquinolones are rapidly emerging as important drugs in the treatment of tuberculosis (TB) worldwide [1]. In drug-susceptible TB, their use is currently under investigation and, according to the American Thoracic Society/Centers for Disease Control guidelines, fluoroquinolones are indicated only in patients receiving the conventional regimen who present severe adverse reactions [2]. However, in drug-resistant (DR) and, more specifically, in multidrug-resistant (MDR)-TB, the role of fluoroquinolones is much better established. Later-generation fluoroquinolones are included even in extensively drug resistant (XDR)-TB regimens since they may have some efficacy against ofloxacin-resistant strains [3]. The area under the concentration–time curve up to 24 h post-dosage (AUC24) is generally considered as the best predictor of fluoroquinolone efficacy [1]. Among fluoroquinolones, moxifloxacin is considered the most bactericidal, with potency comparable to that of isoniazid, and also seems to have some sterilising activity [1]. The maximal concentration (Cmax) of moxifloxacin exceeds mutant prevention concentration [1] and the currently recommended dose of 400 mg is likely to suppress the emergence of resistance in 60% of patients [4]. However, pharmacokinetic data on moxifloxacin in patients with TB are scarce, especially in the setting of an MDR-TB regimen. In this report of a pilot prospective study, we present preliminary data on pharmacokinetic parameters in patients with MDR- or XDR-TB receiving second-line treatment. Patients were receiving moxifloxacin (Avelox®; Bayer, Leverkusen, Germany) p.o. for ≥4 days, in order to achieve a steady state, as part of their anti-TB treatment, which was based on drug susceptibility test results. Quinolone resistance was determined by ofloxacin …