***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: BACKGROUND Aztreonam lysine for inhalation ( AZLI ) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection . METHODS This double-blind , r and omized , placebo-controlled Phase 2 study evaluated the safety , tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow Electronic Nebulizer ( Pari Innovative Manufacturers , Inc. , Midlothian , VA ) . Patients were 13 years and older with FEV1>or=40 % predicted , chronic P. aeruginosa infection , and had used no anti-pseudomonal antibiotics for 56 days . RESULTS Of 131 patients screened , 105 received AZLI or placebo . Mean age was 26 years and mean FEV1 percent predicted was 77 % at baseline . There was a statistically significant reduction , compared to placebo , in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 ( P<0.001 ) . The planned primary analysis , percent change in FEV1 at Day 14 , demonstrated no statistically significant difference . Post hoc analysis demonstrated significant increase in FEV1 at Day 7 for the subset of patients with baseline FEV1<75 % predicted in the 225 mg AZLI group . Bronchodilator use was associated with greater improvement in FEV1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group . Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group . CONCLUSION These data support the further development of AZLI and provide information for the design of subsequent studies Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis ( CF ) patients during a recent clinical trial of inhaled tobramycin . Impermeability , in which bacteria have reduced susceptibility to all aminoglycosides , was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol . Enzymatic resistance mechanisms were found in fewer than 10 % of resistant isolates . P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness . When enzymatic resistance was involved , all isolates in a group had elevated tobramycin MICs . When impermeability occurred , MICs of a genotypic group varied from susceptible to resistant . These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC STUDY OBJECTIVE To determine the effect of long-term suppression of Pseudomonas aeruginosa on lung function and other clinical end points in adolescent patients with cystic fibrosis ( CF ) . DESIGN Two identical , r and omized , placebo-controlled trials followed by three open-label follow-on trials . SETTING Sixty-nine CF study centers in the United States . INTERVENTIONS Active drug consisting of a 300-mg tobramycin solution for inhalation ( TSI ) . PATIENTS One hundred twenty-eight adolescent CF patients ( aged 13 to 17 years ) with P aeruginosa and mild-to-moderate lung disease ( FEV(1 ) percent predicted > or = 25 % and < or = 75 % ) . MEASUREMENTS Pulmonary function , P aeruginosa colony forming unit density , incidence of hospitalization and IV antibiotic use , weight gain , and aminoglycoside toxicity were monitored . RESULTS At the end of the first three 28-day cycles of TSI treatment , patients originally r and omized to TSI and placebo treatments exhibited improvements in FEV(1 ) percent predicted of 13.5 % and 9.4 % , respectively . FEV(1 ) percent predicted was maintained above the value at initiation of TSI treatment in both groups . At the end of the last " on-drug " period ( 92 weeks ) , patients originally r and omized to TSI and placebo treatments showed improvements of 14.3 % and 1.8 % , respectively . Improvement in pulmonary function was significantly correlated with reduction in P aeruginosa colony forming unit density ( p = 0.0001 ) . The average number of hospitalizations and IV antibiotic courses did not increase over time . TSI treatment was associated with increased weight gain and body mass index . P aeruginosa susceptibility to tobramycin decreased slightly over time , but this was not correlated with clinical response . CONCLUSIONS TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term , intermittent use We report the results of a clinical trial . Patients enrolled had serum IgG titres against Pseudomonas aeruginosa above the control range . Assignment to the observation or treatment group was by minimisation . Significant signs or symptoms in any patient prompted antipseudomonal treatment . In addition , the treatment group received antipseudomonal treatment at intervals of four months until the serum IgG titre returned to the control range . P aeruginosa was isolated intermittently from patients in the main trial . Nineteen patients were enrolled ( 12 observation , seven treatment ) . After one year in the trial changes in parameters studied , including forced expiratory volume in one second , IgG titre , serum IgG concentrations , and frequency of P aeruginosa isolation had improved in the treated group and worsened in the observation group OBJECTIVES This r and omized , double-blind , cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis ( CF ) infected with Pseudomonas aeruginosa with and without airway hyperreactivity . DESIGN Of 19 children with CF ( age range , 7 to 16 years ) with mild-to-moderate pulmonary disease , 10 children were at high risk ( HR ) for bronchospasm ( family history of asthma and previous response to bronchodilators ) and 9 children were at low risk ( LR ) for bronchospasm ( no family history of asthma or previous response to bronchodilators ) . Two solutions of tobramycin were administered : ( 1 ) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites ( IV preparation ) ; and ( 2 ) 300 mg in a preservative-free preparation in a 5-mL solution . Following a bronchodilator-free period of 12 h , the patients inhaled either one or the other preparation in r and om order on two different occasions , 2 weeks apart . RESULTS Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1 ) ( DeltaFEV(1 ) ) of 12 + /- 9 % ( mean + /- SD ) for the IV preparation , compared to 4 + /- 5 % for the preservative-free preparation ( p = 0.046 ) . An DeltaFEV(1 ) of > 10 % was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation . For the HR group , the DeltaFEV(1 ) was 17 + /- 13 % for the IV-preparation group , compared to 16 + /- 12 % for the preservative-free group ( p = 0.4 ) . In this group , equal numbers of patients ( 8 of 10 patients ) had an DeltaFEV(1 ) > 10 % after inhaling each preparation . The largest DeltaFEV(1 ) was 44 % ( HR group with the preservative-free preparation that forced the early termination of inhalation ) . CONCLUSIONS Both preparations caused significant bronchoconstriction in the HR group , and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution . Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis ( CF ) , antibiotic therapy generally fails to eradicate the bacterial pathogen . The mucoid bacterial phenotype , high sputum production by the host , and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy . We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection . In a prospect i ve placebo-controlled , double-blind , r and omized multicenter study , 22 CF patients received either 80 mg b.i.d . of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization . Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period . Using life table analysis , the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group ( P < 0.05 , log rank test ) . Lung function parameters and markers of inflammation did not change in either group during treatment . The results of this study suggest that early tobramycin inhalation may prevent and /or delay P. aeruginosa pulmonary infection in CF patients Abstract Background and aim Progressive respiratory failure due to Pseudomonas aeruginosa colonization is the most significant morbidity in patients with cystic fibrosis ( CF ) . This trial was design ed to investigate the efficacy and safety of a highly concentrated ( 300mg/4mL ) tobramycin solution for inhalation ( TSI ) [ Bramitob ® ] in patients with CF and P. aeruginosa infection . Methods Fifty-nine patients were r and omized to receive a 4-week treatment with tobramycin or placebo administered twice daily via the Pari LC Plus ® nebulizer and Pari TurboBoy ™ compressor , followed by a 4-week run-out phase . Pulmonary function ( forced expiratory volume in 1 second [ FEV1 ] , forced vital capacity [ FVC ] , and forced expiratory flow at the midportion of vital capacity [ FEF25–75 % ] ) , P. aeruginosa susceptibility , microbiologic results , and in vitro minimum inhibitory concentration for 90 % of strains ( MIC90 ) were the efficacy outcome measures , while safety was monitored by the recording of adverse events , audiometry ( bone conduction at 250–8000Hz frequency ) , laboratory tests , physical examination and general health condition . The concentration of tobramycin attained in sputum was measured in a cohort of 21 patients . Results FEV1 significantly increased from baseline in the tobramycin group compared with no change in the placebo group : the absolute difference between groups ( intent-to-treat population ) of predicted normal was 13.2 % at week 2 ( p = 0.002 ) and 13.3 % at week 4 ( p = 0.003 ) . Significant differences in favor of the tobramycin group were also observed for FVC and FEF25–75 % . The microbiologic results at the end of the treatment period ( P. aeruginosa-negative culture , persistence , superinfection ) showed a significantly better outcome in the tobramycin group compared with placebo ( p = 0.033 ) . The effects of tobramycin on pulmonary function and microbiology were not maintained at the end of the run-out phase . Mean sputum concentrations of tobramycin after the first dose ( 695.6 ± 817.0 µg/mL ) were similar to those measured after the last dose ( 716.9 ± 799 µg/mL ) and were superior to the detected specific MIC90.The proportion of patients with drug-related adverse events was lower in the tobramycin group and no signs of renal or auditory toxicity were observed . Conclusions The 4-week administration of a highly concentrated TSI significantly improved pulmonary function and microbiologic outcome compared with placebo and was well tolerated . The results of this study should be confirmed in further long-term trials in larger population BACKGROUND AND METHODS We conducted two multicenter , double-blind , placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection . A total of 520 patients ( mean age , 21 years ) were r and omly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks , followed by four weeks with no study drug . Patients received treatment or placebo in three on-off cycles for a total of 24 weeks . The end points included pulmonary function , the density of P. aeruginosa in sputum , and hospitalization . RESULTS The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second ( FEV1 ) of 10 percent at week 20 as compared with week 0 , whereas the patients receiving placebo had a 2 percent decline in FEV1 ( P<0.001 ) . In the tobramycin group , the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units ( CFU ) per gram of expectorated sputum from week 0 to week 20 , as compared with an increase of 0.3 log10 CFU per gram in the placebo group ( P<0.001 ) . The patients in the tobramycin group were  
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There is insufficient evidence to determine whether antibiotic strategies for the eradication of early P. aeruginosa decrease mortality or morbidity , improve quality of life , or are associated with adverse effects compared to placebo or st and ard treatment .
From the three trials included in this review , there is some evidence that antibiotic treatment of early P. aeruginosa results in short-term eradication but it remains uncertain whether there is clinical benefit to people with cystic fibrosis