The value of biofilm testing to guide antimicrobial stewardship in chronic respiratory diseases.

Introduction: Biofilm production is an important yet currently overlooked aspect of diagnostic microbiology that has implications for antimicrobial stewardship. In this study, we aimed to validate and identify additional applications of the BioFilm Ring Test® (BRT) for Pseudomonas aeruginosa (PA) isolates from patients with bronchiectasis (BE). Materials and methods: Sputa were collected from BE patients who had at least one PA positive culture in the previous year. We processed the sputa to isolate both mucoid and non-mucoid PA, and determined their susceptibility pattern, mucA gene status, and presence of ciprofloxacin mutations in QRDR genes. The Biofilm production index (BPI) was obtained at 5 and 24 hours. Biofilms were imaged using Gram staining. Results: We collected 69 PA isolates, including 33 mucoid and 36 non-mucoid. A BPI value below 14.75 at 5 hours predicted the mucoid PA phenotype with 64% sensitivity and 72% specificity. Conclusion: Overall, our findings suggest that the fitness-cost associated with the mucoid phenotype or ciprofloxacin resistance is shown through a time-dependent BPI profile. The BRT has the potential to reveal biofilm features with clinical implications.

Future Directions in Bronchiectasis Research.

Bronchiectasis treatment is challenging, and many recent randomized controlled trials have failed to prove any clinical improvement. The most reasonable explanation for that problem is the high heterogeneity of patients' groups. For that reason, there is an urgent need to find new biomarkers to better stratify patients. The present chapter addresses the future directions in biomarkers, omics technologies, endotypes, and new treatments toward a personalized medicine in the field of bronchiectasis.

Resistance mechanisms and molecular epidemiology of Pseudomonas aeruginosa strains from patients with bronchiectasis.

BACKGROUND: Non-cystic fibrosis bronchiectasis (BE) is a chronic structural lung condition that facilitates chronic colonization by different microorganisms and courses with recurrent respiratory infections and frequent exacerbations. One of the main pathogens involved in BE is Pseudomonas aeruginosa. OBJECTIVES: To determine the molecular mechanisms of resistance and the molecular epidemiology of P. aeruginosa strains isolated from patients with BE. METHODS: A total of 43 strains of P. aeruginosa were isolated from the sputum of BE patients. Susceptibility to the following antimicrobials was analysed: ciprofloxacin, meropenem, imipenem, amikacin, tobramycin, aztreonam, piperacillin/tazobactam, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, cefepime and colistin. The resistance mechanisms present in each strain were assessed by PCR, sequencing and quantitative RT-PCR. Molecular epidemiology was determined by MLST. Phylogenetic analysis was carried out using the eBURST algorithm. RESULTS: High levels of resistance to ciprofloxacin (44.19%) were found. Mutations in the gyrA, gyrB, parC and parE genes were detected in ciprofloxacin-resistant P. aeruginosa strains. The number of mutated QRDR genes was related to increased MIC. Different ß-lactamases were detected: blaOXA50, blaGES-2, blaIMI-2 and blaGIM-1. The aac(3)-Ia, aac(3)-Ic, aac(6″)-Ib and ant(2″)-Ia genes were associated with aminoglycoside-resistant strains. The gene expression analysis showed overproduction of the MexAB-OprM efflux system (46.5%) over the other efflux system. The most frequently detected clones were ST619, ST676, ST532 and ST109. CONCLUSIONS: Resistance to first-line antimicrobials recommended in BE guidelines could threaten the treatment of BE and the eradication of P. aeruginosa, contributing to chronic infection.

Development and characterization of a new swine model of invasive pneumococcal pneumonia.

Streptococcus pneumoniae is the most common microbial cause of community-acquired pneumonia. Currently, there are no available models of severe pneumococcal pneumonia in mechanically ventilated animals to mimic clinical conditions of critically ill patients. We studied endogenous pulmonary flora in 4 healthy pigs and in an additional 10 pigs in which we intra-bronchially instilled S. pneumoniae serotype 19 A, characterized by its resistance to penicillin, macrolides and tetracyclines. The pigs underwent ventilation for 72 h. All pigs that were not challenged with S. pneumoniae completed the 72-h study, whereas 30% of infected pigs did not. At 24 h, we clinically confirmed pneumonia in the infected pigs; upon necropsy, we sampled lung tissue for microbiological/histological confirmation of pneumococcal pneumonia. In control pigs, Streptococcus suis and Staphylococcus aureus were the most commonly encountered pathogens, and their lung tissue mean ± s.e.m. concentration was 7.94 ± 20 c.f.u./g. In infected pigs, S. pneumoniae was found in the lungs of all pigs (mean ± s.e.m. pulmonary concentration of 1.26 × 105 ± 2 × 102 c.f.u./g). Bacteremia was found in 50% of infected pigs. Pneumococcal pneumonia was confirmed in all infected pigs at 24 h. Pneumonia was associated with thrombocytopenia, an increase in prothrombin time, cardiac output and vasopressor dependency index and a decrease in systemic vascular resistance. Upon necropsy, microbiological/histological pneumococcal pneumonia was confirmed in 8 of 10 pigs. We have therefore developed a novel model of penicillin- and macrolide-resistant pneumococcal pneumonia in mechanically ventilated pigs with bacteremia and severe hemodynamic compromise. The model could prove valuable for appraising the pathogenesis of pneumococcal pneumonia, the effects associated with macrolide resistance and the outcomes related to the use of new diagnostic strategies and antibiotic or complementary therapies.

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency.

BACKGROUND: Selective IgE deficiency (SIgED) has been previously evaluated in selected patients from allergy units. This study investigates the effects of SIgED on the entire population in a hospital setting and sought to delineate in detail the clinical aspects of SIgED. METHODS: A retrospective study of the data obtained from electronic medical records of 52 adult patients (56% female) with a mean age of 43 years and IgE levels of <2.0 kU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels, seen at our hospital, without selection bias, from 2010 to 2019. RESULTS: Recurrent upper respiratory infections were recorded in 18 (34.6%) patients, pneumonia was recorded in 16 (30.7%) patients, bronchiectasis was recorded in 16 (30.7%) patients, and asthma was recorded in 10 (19.2%) patients. Eighteen patients (34.6%) suffered autoimmune clinical manifestations either isolated (19%) or combining two or more diseases (15%), Hashimoto's thyroiditis being the most frequent (19%), which was followed by arthritis (10%) and thrombocytopenia and/or neutropenia (5.7%). Other less frequent associations were Graves' disease, primary sclerosing cholangitis, Sjögren's syndrome, and autoimmune hepatitis. Eczematous dermatitis (15.3%), chronic spontaneous urticaria (17.3%), and symptoms of enteropathy (21%) were also highly prevalent. Thirty percent of patients developed malignancies, with non-Hodgkin lymphomas (13.4%) being the most prevalent. CONCLUSIONS: The clinical manifestations of SIgED encompass a variety of infectious, non-infectious complications, and malignancy. Since it cannot be ruled out that some type of selection bias occurred in the routine assessment of IgE serum Ievels, prospective studies are required to better characterize SIgED and to determine whether it should be added to the list of antibody deficiencies.

Pseudomonas aeruginosa in Bronchiectasis.

Pseudomonas aeruginosa (PA) in patients with bronchiectasis (BE) is associated with a poor outcome and quality of life, and its presence is considered a marker of disease severity. This opportunistic pathogen is known for its ability to produce biofilms on biotic or abiotic surfaces and to survive environmental stress exerted by antimicrobials, inflammation, and nutrient or oxygen depletion. The presence of PA biofilms has been linked to chronic respiratory infection in cystic fibrosis but not in BE. There is considerable inconsistency in the reported infection/eradication rates of PA and chronic PA. In addition, inadequate antimicrobial treatment may potentiate the progression from intermittent to chronic infection and also the emergence of antibiotic resistance. A better comprehension of the pathophysiology of PA infections and its implications for BE is urgently needed. This can drive improvements in diagnostic accuracy, can move us toward a new consensus definition of chronic infection, can better define the follow-up of patients at risk of PA, and can achieve more successful eradication rates. In addition, the new technological advances regarding molecular diagnostics, -omics, and biomarkers require us to reconsider our traditional concepts.

Exacerbations and Changes in Physical Activity and Sedentary Behaviour in Patients with Bronchiectasis after 1 Year.

BACKGROUND: Low physical activity and high sedentary behaviour in patients with bronchiectasis are associated with hospitalisation over one year. However, the factors associated with longitudinal changes in physical activity and sedentary behaviour have not been explored. We aimed to identify clinical and sociodemographic characteristics related to a change in physical activity and sedentary behaviour in patients with bronchiectasis after one year. METHODS: This was a prospective observational study during which physical activity measurements were recorded using a SenseWear Armband for one week at baseline and at one year. At each assessment point, patients were classified as active or inactive (measured as steps per day) and as sedentary or not sedentary (measured as sedentary time). RESULTS: 53 patients with bronchiectasis were analysed, and after one year, 18 (34%) had worse activity and sedentary levels. Specifically, 10 patients became inactive and sedentary. Multivariable analysis showed that the number of exacerbations during the follow-up period was the only outcome independently associated with change to higher inactivity and sedentary behaviour (odds ratio (OR), 2.19; 95% CI, 1.12 to 4.28). CONCLUSIONS: The number of exacerbations in patients with bronchiectasis was associated with changes in physical activity and sedentary behaviour. Exacerbation prevention may appear as a key factor in relation to physical activity and sedentary behaviour in patients with bronchiectasis.

The Value of C-Reactive Protein-to-Lymphocyte Ratio in Predicting the Severity of SARS-CoV-2 Pneumonia / Valor del ratio proteína C-reactiva-linfocitos para predecir la gravedad de la neumonía causada por SARS-CoV-2

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Short-Term Effects of Appropriate Empirical Antimicrobial Treatment with Ceftolozane/Tazobactam in a Swine Model of Nosocomial Pneumonia.

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR Pseudomonas aeruginosa pneumonia. Twenty-one pigs with pneumonia caused by an XDR P. aeruginosa strain (susceptible to C/T but resistant to TZP) were ventilated for up to 72 h. Twenty-four hours after bacterial challenge, animals were randomized to receive 2-day treatment with either intravenous saline (untreated) or 25 to 50 mg of C/T per kg body weight (AEAT) or 200 to 225 mg of TZP per kg (IEAT) every 8 h. The primary outcome was the P. aeruginosa burden in lung tissue and the histopathology injury. P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage (BAL) fluid, the development of antibiotic resistance, and inflammatory markers were secondary outcomes. Overall, P. aeruginosa lung burden was 5.30 (range, 4.00 to 6.30), 4.04 (3.64 to 4.51), and 4.04 (3.05 to 4.88) log10CFU/g in the untreated, AEAT, and IEAT groups, respectively (P = 0.299), without histopathological differences (P = 0.556). In contrast, in tracheal secretions (P < 0.001) and BAL fluid (P = 0.002), bactericidal efficacy was higher in the AEAT group. An increased MIC to TZP was found in 3 animals, while resistance to C/T did not develop. Interleukin-1ß (IL-1ß) was significantly downregulated by AEAT in comparison to other groups (P = 0.031). In a mechanically ventilated swine model of XDR P. aeruginosa pneumonia, appropriate initial treatment with C/T decreased respiratory secretions' bacterial burden, prevented development of resistance, achieved the pharmacodynamic target, and may have reduced systemic inflammation. However, after only 2 days of treatment, P. aeruginosa tissue concentrations were moderately affected.

Aetiological diagnosis in new adult outpatients with bronchiectasis:role of predictors derived from real life experience.

BACKGROUND: In adult patients with bronchiectasis (BE) the identification of the underlying aetiology may be difficult. In a new patient with BE the performance of a panel of tests is recommended, even though this practice may be expensive and the level of evidence supporting is low. We aimed to identify a panel of variables able to predict the aetiological diagnosis of BE. METHODS: Our prospective study derived from our real-life experience on the management of adult stable BE outpatients. We recorded variables concerning clinical, radiological, microbiological and laboratory features. We identified five groups of aetiological diagnosis of BE (idiopathic, post-infective, COPD, asthma and non-common diseases [immunodeficiency or other rare conditions]). Multivariate models were used to identify predictors of each aetiological diagnosis. The suitability of performing a specific test for the diagnosis was also considered. RESULTS: We enrolled 354 patients with a new diagnosis of BE. Patients with different aetiological causes differed significantly with regard to age, sex, smoking habit, comorbidities, dyspnoea perception, airflow obstruction and severity scores. Various predictors were assessed, including sex, previous respiratory infections, diffuse localization of BE, risk scores, and laboratory variables (sodium and eosinophils). The levels of autoantibodies or immunoglobulins were reserved for the diagnosis of non-common disease. CONCLUSION: Our research confirms that some predictors are specific for the aetiological diagnosis of BE. The possibility of integrating this information may represent a useful tool for the diagnosis. The execution of certain specific tests should be reserved for patients with a non-common disease.

Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa.

Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1ß, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1ß, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.

Association between physical activity and risk of hospitalisation in bronchiectasis.

BACKGROUND: Patients with bronchiectasis have a less active lifestyle than healthy peers, but the association with hospital admission has not been explored. The aim of this study was to investigate the association between 1) any physical activity variable; and 2) sedentary time, with hospitalisation due to exacerbation in adults with bronchiectasis. METHODS: In this prospective observational study, baseline lung function, quality of life, exercise tolerance, severity of bronchiectasis and physical activity were recorded. Physical activity was objectively assessed over a week using a SenseWear armband and the results were expressed in steps·day-1 and sedentary time. Number of hospitalisations due to a bronchiectasis exacerbation and time to first event were recorded after 1-year follow-up. RESULTS: Sixty-four patients with bronchiectasis were analysed, of whom 15 (23%) were hospitalised during the follow-up. Hospitalised patients showed poor baseline clinical and severity outcomes, fewer steps walked per day and more sedentary behaviour than the non-hospitalised group. Patients who walked ≤6290 steps·day-1 or spent ≥7.8 h·day-1 in sedentary behaviour had an increased risk of hospital admission due to bronchiectasis exacerbation at 1-year follow-up. Specifically, ≥7.8 h·day-1 of sedentary behaviour was associated with a 5.9-fold higher risk of hospital admission in the following year. CONCLUSIONS: Low levels of physical activity and high sedentary time at baseline were associated with a higher risk of hospitalisation due to bronchiectasis exacerbation. If these findings are validated in future studies, it might be appropriate to include physical activity and sedentary behaviour as an item in severity scores.

Ceftaroline for severe community-acquired pneumonia: A real-world two-centre experience in Italy and Spain.

BACKGROUND: Ceftaroline is one of latest additions to the armamentarium for treating community-acquired pneumonia (CAP). This study aimed to describe the outcome of severe CAP (SCAP) in a cohort of hospitalised patients treated with ceftaroline. METHODS: A retrospective, observational study of patients with SCAP treated with ceftaroline in two hospitals in Spain and Italy. The primary objective was to explore 30-day mortality after diagnosis of SCAP. RESULTS: During the study period the following were observed: there were 89 cases of SCAP treated with ceftaroline and 53 cases used in combination with other antibiotics (60%). Overall, 30-day mortality and clinical failure were 20% (18 of 89) and 36% (32 of 89), respectively. Independent predictors of 30-day mortality were: increasing age (OR for 1 year increase 1.0, 95% CI 1.0-1.1, P 0.043), presence of solid neoplasm (OR 4.0, 95% CI 1.0-15.1, P 0.044) and concomitant therapy with oseltamivir (OR 8.5, 95% CI 1.2°57.3, P 0.029). The only independent predictor of clinical failure was the time elapsing from SCAP diagnosis to ceftaroline therapy (OR for each passing day 1.5, 95% CI 1.1-1.9, P 0.003). The clinical success rate was 64% (57 of 89). In the subgroups of patients with proven Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infection, clinical success was 83% (10 of 12), 75% (three of four) and 56% (five of nine), respectively. CONCLUSIONS: Considering its spectrum of activity, ceftaroline could represent an important therapeutic option for SCAP. Further studies are needed to identify the precise clinical success rate against MRSA in a larger cohort of patients with SCAP.

Clinical Factors Associated with a Shorter or Longer Course of Antibiotic Treatment in Patients with Exacerbations of Bronchiectasis: A Prospective Cohort Study.

BACKGROUND: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even though there is limited evidence for this approach. We therefore aimed to investigate the baseline clinical and microbiological findings associated with long courses of antibiotic treatment in exacerbated bronchiectasis patients. METHODS: This was a bi-centric prospective observational study of bronchiectasis exacerbated adults. We compared groups receiving short (≤14 days) and long (15-21 days) courses of antibiotic treatment. RESULTS: We enrolled 191 patients (mean age 72 (63, 79) years; 108 (56.5%) females), of whom 132 (69%) and 59 (31%) received short and long courses of antibiotics, respectively. Multivariable logistic regression of the baseline variables showed that long-term oxygen therapy (LTOT), moderate-severe exacerbations, and microbiological isolation of Pseudomonas aeruginosa were associated with long courses of antibiotic therapy. When we excluded patients with a diagnosis of community-acquired pneumonia (n = 49), in the model we found that an etiology of P. aeruginosa remained as factor associated with longer antibiotic treatment, with a moderate and a severe FACED score and the presence of arrhythmia as comorbidity at baseline. CONCLUSIONS: Decisions about the duration of antibiotic therapy should be guided by clinical and microbiological assessments of patients with infective exacerbations.

Nebulized Amikacin and Fosfomycin for Severe Pseudomonas aeruginosa Pneumonia: An Experimental Study.

OBJECTIVES: Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem. DESIGN: Prospective randomized animal study. SETTING: Animal Research, University of Barcelona, Spain. SUBJECTS: Thirty female pigs. INTERVENTIONS: The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance. MEASUREMENTS AND MAIN RESULTS: We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004). CONCLUSIONS: Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.

¿Cómo realizamos el cribado de infección tuberculosa latente en pacientes candidatos a terapias biológicas en España? Una encuesta multidisciplinar / Screening for Latent Tuberculosis Infection in Patients who are Candidate for Biological Therapies in Spain? A Multidisciplinary Survey

Introducción: El tratamiento con terapias biológicas aumenta la incidencia de enfermedad tuberculosa. La implementación sistemática del cribado de la infección tuberculosa latente en pacientes que van a recibir estas terapias ha conseguido reducir el riesgo de desarrollarla. En 2016 se publicó en España el Documento de consenso sobre la prevención y el tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. El objetivo principal del estudio fue evaluar la adherencia al mismo. Métodos: Estudio multicéntrico, descriptivo, observacional en forma de encuesta anónima online, difundida entre las diferentes sociedades médicas que trabajan con biológicos. Resultados: Se recibieron 747 respuestas. La mayoría de los encuestados realizaba el cribado en el momento adecuado y con la indicación correcta (93,7%). Solo un 36,6% de los encuestados solicitaba las pruebas diagnósticas adecuadas, mientras que el 56,3% acertaron las indicaciones de quimioprofilaxis. Hasta el 96% conocía las pautas de quimioprofilaxis recomendadas, mientras que solo el 63,9% las iniciaba en el momento adecuado. La especialidad con más participación y que más realizaba el cribado de infección tuberculosa latente fue reumatología (54%). En la mayoría de los casos, los neumólogos participaban como consultores. Conclusiones: Este estudio pone de manifiesto un bajo grado de adherencia a las recomendaciones, realizando un cumplimiento aceptable el 56% de los encuestados. Enfatizando en las pruebas diagnósticas adecuadas y en el algoritmo diagnóstico de infección tuberculosa latente, se podría reducir aún más la incidencia de enfermedad tuberculosa en los pacientes que van a recibir terapias biológicas

Introduction: Treatment with biological therapies increases the incidence of tuberculous disease. The introduction of systematic screening for latent tuberculosis infection in patients who are to receive these therapies has reduced this risk. In 2016, the consensus document on the prevention and treatment of tuberculosis in patients who are candidates for biological treatment was published in Spain. The main objective of this study was to evaluate adherence to these guidelines. Methods: Multicenter, descriptive, observational study via an anonymous online survey sent to medical societies involved in biologics. Results: We received 747 responses. Most respondents performed screening at the right time in the right patients (93.7%). Only 36.6% of respondents requested the appropriate diagnostic test, while 56.3% correctly recommended chemoprophylaxis. Up to 96% were familiar with the recommended chemoprophylaxis regimens, while only 63.9% initiated them at the right time. The specialist area that participated most and screened most patients for latent tuberculosis infection was rheumatology (54%). In most cases, pulmonologists were involved in an advisory capacity. Conclusions: This study shows poor overall adherence to recommendations, with only 56% of respondents reporting appropriate compliance. The incidence of tuberculous disease in patients who are to receive biological therapies could be reduced further by emphasizing the importance of the right diagnostic test and use of the diagnostic algorithm for latent tuberculosis infection

The efficacy of inhaled antibiotics in non-cystic fibrosis bronchiectasis.

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is considered a chronic heterogenic pulmonary disease, characterized by the permanent and abnormal enlargement and thickening of bronchial walls, impaired mucociliary clearance, and suppuration. Inhaled antibiotics have been used for a long time in patients with cystic fibrosis but are seldom used in those with NCFB and few randomized clinical trials are available in this population. Areas covered: This review summarizes current clinical evidence of efficacy, adverse events, and future directions of inhaled antibiotics in NCFB. Expert commentary: Inhaled antibiotics are theoretically a promising therapeutic option for patients with NCFB, owing to the achieved high pulmonary concentrations and the irrelevant systemic adverse effects. In the era of multidrug resistance, we call for comprehensive clinical trials in this field to corroborate the merits of inhaled antibiotics in NCFB patients.