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.

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.

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.

Impact of Hypertonic Saline Solutions on Sputum Expectoration and Their Safety Profile in Patients with Bronchiectasis: A Randomized Crossover Trial.

BACKGROUND: The role of hyaluronic acid plus hypertonic saline (HA+HS) as a mucoactive treatment in patients with bronchiectasis is still unknown. This study evaluated whether HA+HS solution enhances similar sputum quantity with better safety profile than HS alone in patients with bronchiectasis. METHODS: In this double-blind randomized crossover trial, three solutions (7% HS; 0.1% HA +7%HS; and 0.9% isotonic saline, IS) were compared in outpatients with bronchiectasis and chronic sputum expectoration. Participants inhaled each solution across four consecutive sessions. All sessions, except on session 3, also included 30 minutes of airway clearance technique. A 7-day washout period was applied. Sputum weight was collected during the sessions (primary outcome) as well as during a 24-hour follow-up. The Leicester Cough Questionnaire (LCQ) and lung function were measured before/after each treatment arm. Safety was assessed by the monitoring of adverse events (AEs). RESULTS: Twenty-eight patients with bronchiectasis (mean age of 64.0 (17.9) and FEV1% 60.9 (24.6) of predicted) were recruited. HS and HA+HS promoted similar expectoration during sessions, both being greater than IS [median difference HS vs. IS 3.7 g (95% CI 0.5-6.9); HA+HS vs. IS 3.2 g (95%CI 0.5-5.9)]. Sputum expectorated exclusively during the ACT period was similar across all treatment arms [HS vs. IS -0.3 g (95% CI -1.7 to 0.9); HA+HS vs. IS 0.0 g (95% CI -1.3 to 1.4); HS vs. HA+HS 0.0 g (95% CI -1.2 to 0.4)]. Sputum collected over the 24-hour follow-up tended to be lower for HS and HA+HS compared with IS [HS vs. IS -1.7 g (95% CI -4.2 to 0.0); HA+HS vs. IS -1.1 g (95%CI -3.6 to 0.7)]. No differences in LCQ or lung function were observed. Most severe AEs were reported using HS. CONCLUSION: HS and HA+HS were more effective on sputum expectoration than IS in patients with bronchiectasis, reporting HA+HS better safety profile than HS.

Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations.

BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more susceptible to acquire pathogens with antibiotic resistance. We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations. METHODS: A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared. Multidrug-resistance was determined according to European Centre of Diseases Prevention and Control classification. RESULTS: Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes. Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016). Three independent multidrug-resistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92-30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37-11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02-15.46). The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors. CONCLUSIONS: Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations. This information may assist clinicians in choosing empirical antibiotics in daily clinical practice.

Comparison of two prognostic scores (BSI and FACED) in a Spanish cohort of adult patients with bronchiectasis and improvement of the FACED predictive capacity for exacerbations.

Bronchiectasis (BE) is a chronic and heterogeneous respiratory disease that requires a multidimensional scoring system to properly assess severity. The aim of this study was to compare the severity stratification by 2 validated scores (BSI and FACED) in a BE cohort and to determine their predictive capacity for exacerbations and hospitalizations. Moreover, we proposed a modified version of FACED which was created to better predict the risk of exacerbations in clinical practice. We performed a prospective cohort study including BE patients >18 years old with a follow-up period of 1-year. One-hundred eighty-two patients (40% males; mean age 68) were studied. Patients were stratified according to the number of exacerbations during the follow-up, and according to BSI and FACED scores. BSI classified most of our patients as severe 99 (54.4%) or moderate 47 (25.8%), while FACED mainly classified as mild 108 (59.3%) or moderate 61 (33.5%). BSI and FACED showed an area under ROC curve (AUC) for exacerbations of 0.808 and 0.734; and for hospitalizations (due to BE exacerbations) of 0.893 and 0.809, respectively. Subsequently, we modified FACED by adding previous exacerbations (Exa-FACED) and this new score classified patients as mild 48.4%, moderate 34.6% and severe 17.0%, with an improved AUC for exacerbations (0.760) and hospitalizations (0.820). Despite previous validations of BSI and FACED, they classified our patients very differently. As expected, FACED showed poor prognostic capacity for exacerbations. We support the Exa-FACED score to predict the risk future exacerbations for been easy to use in clinical practice.

Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients.

BACKGROUND: It is general belief that Non-cystic fibrosis bronchiectasis (NCFB) is characterized by frequent community-acquired pneumonia. Nonetheless, the knowledge on clinical characteristics of CAP in NCFBE is poor and no specific recommendations are available. We aim to investigate clinical and microbiological characteristics of NCFBE patients with CAP. METHODS: Prospective observational study of 3495 CAP patients (2000-2011). RESULTS: We found 90 (2.0%) NCFBE-CAP that in comparison with non-bronchiectatic CAP (n, 3405) showed older age (mean ± [SD], NCFBE-CAP 73 ± 14 vs. CAP 65 ± 19yrs), more vaccinations (pneumococcal: 35% vs. 14%; influenza: 60% vs. 42%), comorbidities (n ≥ 2: 43% vs. 25%), previous antibiotics (38% vs. 22%), and inhaled steroids (53% vs. 16%) (p < 0.05 each). Streptococcus pneumoniae was the most frequent isolate in both groups (NCFBE-CAP 44.4% vs. CAP 42.7%; p = 0.821) followed by respiratory virus, mixed infections and atypical bacteria. Considering overall frequencies of the main pathogens (including monomicrobial and mixed infections) Pseudomonas aeruginosa (15.5% vs. 2.9%; p < 0.001) and Enterobacteriaceae (8.8% vs. 2.4%; p = 0.025) were more prevalent in NCFBE-CAP patients than in CAP. Despite these clinical and microbiological differences, NCFBE-CAP showed similar outcomes to CAP patients (mortality, length of hospital stay, etc.). CONCLUSIONS: NCFBE-CAP patients are usually older and have more comorbidities but similar outcomes than general CAP population. Usual CAP pathogens, such as S. pneumoniae, are also involved in NCFBE-CAP but P. aeruginosa and other Enterobacteriaceae were globally more frequent than in CAP. Therefore, a wide microbiological investigation should be recommended in all NCFBE-CAP cases as well as routine pneumococcal vaccination for prevention of pneumonia.