***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency .  Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis ( NCFB ) are to reduce the number of exacerbations , and improve quality of life . However , currently no therapies are licensed for this . Ciprofloxacin Dry Powder for Inhalation ( Ciprofloxacin DPI ) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients . The RESPIRE programme consists of two international phase III prospect i ve , parallel-group , r and omized , double-blinded , multicentre , placebo-controlled trials of the same design . Adult patients with idiopathic or post-infectious NCFB , a history of ≥2 exacerbations in the previous 12months , and positive sputum culture for one of seven pre-specified pathogens , undergo stratified r and omization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5 mg or placebo using a pocket-sized inhaler in one of two regimens : 28days on/off treatment or 14days on/off treatment . The treatment period is 48weeks plus an 8-week follow-up after the last dose . The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation . Secondary endpoints , including frequency of events using different exacerbation definitions , microbiology , quality of life and lung function will also be evaluated . The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI . The strict entry criteria and stratified r and omization , the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy . Additionally RESPIRE will increase underst and ing of NCFB treatment and could lead to an important new therapy for sufferers . TRIAL REGISTRATION The RESPIRE trials are registered in Clinical Trials.gov , ID number NCT01764841 ( RESPIRE 1 ; date of registration January 8 , 2013 ) and NCT02106832 ( RESPIRE 2 ; date of registration April 4 , 2014 ) RATIONALE Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency , a more rapid decline in lung function , and increased mortality in patients with bronchiectasis . OBJECTIVES To perform a r and omized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection . METHODS Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation . Participants were r and omized to receive colistin ( 1 million IU ; n = 73 ) or placebo ( 0.45 % saline ; n = 71 ) via the I-neb twice a day , for up to 6 months . MEASUREMENTS AND MAIN RESULTS The primary endpoint was time to exacerbation . Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb , P. aeruginosa bacterial density , quality of life , and safety parameters . All analyses were on the intention-to-treat population . Median time ( 25 % quartile ) to exacerbation was 165 ( 42 ) versus 111 ( 52 ) days in the colistin and placebo groups , respectively ( P = 0.11 ) . In adherent patients ( adherence quartiles 2 - 4 ) , the median time to exacerbation was 168 ( 65 ) versus 103 ( 37 ) days in the colistin and placebo groups , respectively ( P = 0.038 ) . P. aeruginosa density was reduced after 4 ( P = 0.001 ) and 12 weeks ( P = 0.008 ) and the St. George 's Respiratory Question naire total score was improved after 26 weeks ( P = 0.006 ) in the colistin versus placebo patients , respectively . There were no safety concerns . CONCLUSIONS Although the primary endpoint was not reached , this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection . Clinical trial registered with http://www.is rct n.org/ ( IS RCT N49790596 ) Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use . However , little is known about the wider , potentially adverse impacts of these treatments . Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation , while increases in macrolide resistance carriage would represent a serious public health concern . Using sample s from a r and omized controlled trial , we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota . We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance . Determining the clinical significance of these changes , relative to treatment benefit , now represents a research priority . ABSTRACT Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis . However , little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance . We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis , enrolled in the Bronchiectasis and Low-dose Erythromycin Study ( BLESS ) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate ( 400 mg ) . Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR , respectively . Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae ( P = 0.041 ) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae ( P = 0.024 ) and Actinomyces odontolyticus ( P = 0.027 ) . Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp . ( P = 0.046 ) . Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A ) , erm(B ) , erm(C ) , erm(F ) , mef(A/E ) , and msrA macrolide resistance genes . However , the abundance of erm(B ) and mef(A/E ) gene copies within carriers who had received erythromycin increased significantly ( P < 0.05 ) . Our findings indicate that changes in oropharyngeal microbiota composition result ing from long-term erythromycin treatment are modest and are limited to a discrete group of taxa . Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance . IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use . However , little is known about the wider , potentially adverse impacts of these treatments . Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation , while increases in macrolide resistance carriage would represent a serious public health concern . Using sample s from a r and omized controlled trial , we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota . We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance . Determining the clinical significance of these changes , relative to treatment benefit , now represents a research priority IMPORTANCE Macrolide antibiotics have been shown beneficial in cystic fibrosis ( CF ) and diffuse panbronchiolitis , and earlier findings also suggest a benefit in non-CF bronchiectasis . OBJECTIVE To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis . DESIGN , SETTING , AND PARTICIPANTS The BAT ( Bronchiectasis and Long-term Azithromycin Treatment ) study , a r and omized , double-blind , placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherl and s among 83 out patients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year . INTERVENTIONS Azithromycin ( 250 mg daily ) or placebo for 12 months . MAIN OUTCOME MEASURES Number of infectious exacerbations during 12 months of treatment . Secondary end points included lung function , sputum bacteriology , inflammatory markers , adverse effects , symptom scores , and quality of life . RESULTS Forty-three participants ( 52 % ) received azithromycin and 40 ( 48 % ) received  placebo and were included in the modified intention-to-treat analysis . At end of study , the median number of exacerbations in the azithromycin group was 0 ( interquartile range [ IQR ] , 0 - 1 ) , compared with 2 ( IQR , 1 - 3 ) in the placebo group ( P < .001 ) . Thirty-two ( 80 % ) placebo-treated vs 20 ( 46 % ) azithromycin-treated individuals had at least 1 exacerbation ( hazard ratio , 0.29 [ 95 % CI , 0.16 - 0.51 ] ) . In a mixed-model analysis , change in forced expiratory volume in the first second of expiration ( percent of predicted ) over time differed between groups ( F1,78.8 = 4.085 , P = .047 ) , with an increase of 1.03 % per 3 months in the azithromycin group and a decrease of 0.10 % per 3 months in the placebo group . Gastrointestinal adverse effects occurred in 40 % of patients in the az 
    Output:
    
No r and omised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis .
High- quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations , antibiotic resistance and the occurrence of serious adverse events