You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis.
Abstract 1:
Chronic airway infection with Pseudomonas aeruginosa ( PA ) causes morbidity and mortality in patients with cystic fibrosis ( CF ) . Additional anti-PA therapies are needed to improve health status and health-related quality of life . AIR-CF3 was an international 18-month , open-label study to evaluate the safety and efficacy of repeated courses of aztreonam for inhalation solution ( AZLI , now marketed as Cayston ® ) in patients aged ≥ 6 years with CF and PA infection who previously participated in one of two Phase 3 studies : AIR-CF1 or AIR-CF2 . Patients received up to nine courses ( 28 days on/28 days off ) of 75 mg AZLI two ( BID ) or three times daily ( TID ) based on r and omization in the previous trials . 274 patients , mean age 28.5 years ( range : 8 - 74 years ) , participated . Mean treatment adherence was high ( 92.0 % BID group , 88.0 % TID group ) . Hospitalization rates were low and adverse events were consistent with CF . With each course of AZLI , FEV(1 ) and scores on the Cystic Fibrosis Question naire-Revised Respiratory Symptom scale improved and bacterial density in sputum was reduced . Benefits waned in the 28 days off therapy , but weight gain was sustained over the 18 months . There were no sustained decreases in PA susceptibility . A dose response was observed ; AZLI TID-treated patients demonstrated greater improvements in lung function and respiratory symptoms over 18 months . Repeated intermittent 28-day courses of AZLI treatment were well tolerated . Clinical benefits in pulmonary function , health-related quality of life , and weight were observed with each course of therapy . AZLI is a safe and effective new therapy in patients with CF and PA airway infection


Title 2:
Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients.
Abstract 2:
BACKGROUND Pulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis ( CF ) and it is not well understood why some patients do not respond to antibiotic therapy . The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations . METHODS As a secondary analysis of a r and omized , controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients , we investigated whether baseline factors and changes in sputum bacterial density , serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation . RESULTS In 36 of the 70 exacerbations ( 51 % ) , patients ' lung function returned to > 100 % of their baseline at day 14 of antibiotic treatment ; 34 exacerbations were classified as non-responders . Baseline characteristics were not significantly different between responders and non-responders . Less of a drop in FEV1 from baseline to exacerbation ( OR 1.09 , 95 % CI 1.0 , 1.18 , p=0.04 ) as well as a greater decrease in sputum neutrophil elastase ( OR 2.94 , 95 % CI 1.07 , 8.06 , p=0.04 ) were associated with response to antibiotic treatment at day 14 . In addition , higher CRP ( HR 1.35 ( 95 % CI : 1.01 , 1.78 ) , p=0.04 ) and sputum neutrophil elastase ( HR 1.71 ( 95 % CI : 1.02 , 2.88 ) , p=0.04 ) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation . CONCLUSIONS Inadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients


Title 3:
Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection.
Abstract 3:
RATIONALE In cystic fibrosis ( CF ) , conventional antibiotic susceptibility results correlate poorly with clinical outcomes . We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways . METHODS A multicenter r and omized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinical ly stable adolescent and adult CF patients . Thirty-nine participants were r and omized to biofilm or conventional treatment groups ;  14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results . RESULTS Of the agents tested , meropenem was most active against biofilm-grown bacteria , and was included in regimens for about half of each study group . For 19 of 39 r and omized participants , r and omization to the other study group would not have changed the antibiotic classes of the assigned regimen . Study groups were comparable at baseline , and had similar mean decreases in bacterial density , measured in log(10 ) colony forming units per gram of sputum ( biofilm , -2.94 [ SD 2.83 ] vs. conventional , -3.27 [ SD 3.09 ] ) , and mean increases in forced expiratory volume in 1 sec , measured in liters ( 0.18 [ SD 0.20 ] vs. 0.12 [ SD 0.22 ] ) . CONCLUSIONS In this pilot study , antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses . The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation


Title 4:
Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group.
Abstract 4:
BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated


Title 5:
Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients.
Abstract 5:
This study aim ed to determine whether antimicrobial susceptibility testing of Pseudomonas aeruginosa grown as a biofilm , rather than planktonically , improves efficacy of antibiotic treatment for pulmonary exacerbations . This was a multicenter r and omized , double-blind controlled trial of 14 days of intravenous antibiotic treatment for pulmonary exacerbations chosen based on conventional vs. biofilm antimicrobial susceptibility results in CF patients with chronic P. aeruginosa infection . There were 74 exacerbations in 39 patients . A total of 46 % ( 12/26 ) exacerbations in the conventional group compared to 40 % ( 19/48 ) exacerbations in the biofilm group achieved a ≥3 log drop in P. aeruginosa sputum density ( difference -0.03 , 95 % CI -0.5 to 0.4 , p=0.9 ) . Lung function improvements were similar in both groups . Biofilm antimicrobial susceptibility testing did not lead to improved microbiological or clinical outcomes compared to conventional methods in the treatment of pulmonary exacerbations in CF patients with chronic P. aeruginosa


Title 6:
Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial
Abstract 6:
BACKGROUND We did a r and omised , double-blind , controlled clinical trial to prospect ively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria . METHODS 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic  susceptibility tests using multiple combination bactericidal antibiotic testing ( MCBT ) . Patients who developed an exacerbation of pulmonary disease were r and omised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT . The primary outcome was time from r and omisation until the patient 's next pulmonary exacerbation . Analysis was by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N60187870 . FINDINGS 132 patients had a pulmonary exacerbation and were r and omised during the 4.5-year study period . The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group ( hazard ratio 0.86 in favour of the conventionally-treated group , 95 % CI 0.60 - 1.23 , p=0.40 ) . There was no difference between the groups in treatment failure rate . After 14 days of intravenous antibiotic therapy , changes in lung function , dyspnoea , and sputum bacterial density were similar in both groups . INTERPRETATION Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by st and ard culture and sensitivity techniques . The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations
Although the intervention was shown to be safe , the data from these two trials did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes .
The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis .