***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 Inhaled tobramycin has been shown to transiently clear Pseudomonas from lower airways in early cystic fibrosis ( CF ) , but does not markedly reduce lung inflammation , a key factor in disease progression . OBJECTIVE Test the hypothesis that systemic antibiotics are more effective than inhaled antibiotics for reducing lower airways inflammation . METHODS Clinical ly stable CF children with recent Pseudomonas were r and omized to receive 4 weeks of inhaled tobramycin or 2 weeks of systemic antibiotics ( intravenous ceftazidime and tobramycin ) . Bronchoalveolar lavage fluid was obtained just before and 4 - 6 weeks after treatment . The primary outcome was change in % neutrophils in lavage fluid . RESULTS Fifteen subjects ( inhaled = 6 , systemic = 9 ) completed the protocol . Three Systemic Group subjects could not have central venous access established and were treated with oral ciprofloxacin ( plus inhaled tobramycin ) for 2 weeks as an alternative " systemic " regimen , per protocol . Groups were well matched in age , markers of disease severity , and initial % neutrophils . The Systemic Group showed a modest median change in percent neutrophils ( -7 % ) which was not statistically significant compared to inhaled ( + 5.4 % , P = 0.07 ) . However , the Systemic Group had significantly greater reductions in total cells ( -50 % vs. -3 % , P < 0.01 ) and neutrophils ( -74 % vs. -10 % , P = 0.02 ) per ml lavage fluid . Both groups had reduced bacterial quantity after treatment , but there was no significant difference between groups . CONCLUSIONS In clinical ly stable children with CF , systemic antibiotics result in greater short-term reduction in lower airways inflammation than inhaled antibiotics Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract , completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo . The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo BACKGROUND Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis ( CF ) patients chronically infected with Pseudomonas aeruginosa . Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin . However , nebulized colistin can cause bronchoconstriction in CF patients . Therefore , in the progress of developing a dry powder formula , the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects . To investigate the side effects , a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF- patients . METHODS Nine CF- patients chronically infected with P. aeruginosa participated in a double blind , r and omized cross over study . On two visits to the outpatient clinic , patients were su bmi tted to either nebulized colistin sulphate or colistin sulphomethate solution .  Lung function tests were performed immediately before and 15 and 30 min after nebulization . RESULTS Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate . A significant decrease in mean changes ( SD ) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3 % ( 8.6 % ) , -5.7 % ( 7.3 % ) and -8.4 % ( 7.5 % ) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate ( P < 0.05 ) . Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough . CONCLUSION Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa .  Colistin sulphomethate is the drug of choice for pulmonary administration of colistin A r and omized cross-over study was undertaken to compare nebulized ( 1 ) ceftazidime with ( 2 ) a combination of gentamicin and carbenicillin , and ( 3 ) saline , each given for 4 months , in patients with cystic fibrosis infected with Pseudomonas aeruginosa .  Mean peak expiratory flow on ceftazidime , 299 litres/min , and on gentamicin and carbenicillin , 297 litres/min , were greater than on saline , 278 litres/min ( P less than 0.02 and P less than 0.05 respectively ) . Similarly mean forced expiratory volume in 1 second on ceftazidime , 1.70 litres , and on gentamicin and carbenicillin , 1.70 litres , were greater than on saline , 1.48 litres ( P less than 0.02 and P less than 0.01 respectively ) . Mean forced vital capacity on gentamicin and carbenicillin , 2.93 litres , was also greater than on saline ( P less than 0.05 ) . We were unable to demonstrate any difference in efficacy between the antibiotic regimens . The patients were admitted to hospital less frequently during the study year compared with the previous year ( P less than 0.05 ) . Sixty-nine per cent of patients had a clinical ly significant ( 20 % ) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study , but a minority of patients appear not to respond to this form of treatment 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 The major cause of morbidity and mortality in patients with cystic fibrosis ( CF ) is respiratory disease ( Penketh et al. , Thorax 1987 ; 42 : 526 - 532 ) . Recent studies in the USA have shown that intermittent administration of inhaled tobramycin is beneficial to patients with CF who are chronically infected with Pseudomonas aeruginosa ( Ramsey et al. , N Engl J Med 1999 ; 340 : 23 - 30 ; Ramsey et al. , Proceedings of the 12th Annual North American Cystic Fibrosis Conference , 1998 , Montreal , Canada ; Ramsey et al. , Abstract from 23rd European Cystic Fibrosis Conference , 1999 , the Hague , Netherl and s ) . In Europe , the use of nebulised colistin in patients chronically infected with P. aeruginosa is widespread . A recently published study compared the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients . One hundred and fifteen patients were r and omised to receive either TNS or colistin in a multi-centre open-labelled study that assessed change from baseline in FEV(1 ) and sputum P. aeruginosa density .  TNS produced a mean 6.7 % improvement in lung function ( P=0.006 ) , whilst there was no significant improvement in the colistin-treated patients . The TNS-treated patients had a significantly greater improvement in lung function than those treated with colistin ( P=0.008 ) . The safety profile of both treatments was good . We conclude that patients treated with TNS for 1 month experience improved lung function compared with patients treated with colistin Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis ( CF ) patients . The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients chronically infected with P. aeruginosa . One-hundred and fifteen patients , aged ≥6 yrs , were r and omised to receive either TNS or colistin , twice daily for 4 weeks . The primary end point was an evaluation of the relative change in lung function from baseline , as measured by forced expiratory volume in one second % predicted . Secondary end points included changes in sputum P. aeruginosa density , tobramycin/colistin minimum inhibitory concentrations and safety assessment s.  TNS produced a mean 6.7 % improvement in lung function ( p=0.006 ) , whilst there was no significant improvement in the colistin-treated patients ( mean change 0.37 % ) . Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density , and there was no development of highly resistant strains over the course of the study . The safety profile for both nebulised antibiotics was good . Tobramycin nebuliser solution  significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa , but colistin did not , in this study of 1-month 's duration . Both treatments reduced the bacterial load OBJECTIVES This r and 
    Output:
    
Lung function ( measured as forced expired volume in one second ) was higher and exacerbations of lung infection ( by different measures ) were less in the antibiotic-treated group .
Resistance to antibiotics increased more in the antibiotic-treated group than in placebo group when results were reported .
No auditory or renal impairment was found ; analysis showed tinnitus , voice alteration , hemoptysis and cough were more frequent with tobramycin than placebo .
AUTHORS ' CONCLUSIONS Inhaled antibiotic treatment probably improves lung function and reduces exacerbation rate , but a pooled estimate of the level of benefit is not possible .
The best evidence is for inhaled tobramycin .