***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: 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 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 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 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 BACKGROUND Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment . This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients ' preference . METHODS Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second ( FEV1 ) of 54 % predicted ( range 24 - 98 ) were studied . They inhaled a nebulised solution of hypertonic , isotonic , and hypotonic colistin over three consecutive days in r and om order in a double blind fashion . Measurements of chest tightness , using a visual analogue scale ( VAS ) , and FEV1 were recorded before and 0 , 15 , 30 , 60 , and 90 minutes following inhalation . The solution preferred by each patient was determined at the end of the three days . RESULTS All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness , with no differences between the solutions . However , the mean ( SE ) time to the maximum fall in FEV1 % predicted was significantly different between the solutions ( hypertonic 7.8 ( 2.1 ) min , isotonic 19.2 ( 5.5 ) min , and hypotonic 34.2 ( 5.9 ) min ) with a mean difference ( 95 % CI ) between hypotonic and hypertonic solutions of 28.04 ( 14.6 to 41.5 ) min , between isotonic and hypertonic solutions of 12.0 ( -0.1 to 24.1 ) min , and between hypotonic and isotonic solutions of 15.6 ( 1.8 to 29 
    Output:
    
Lung function measured as forced expired volume in one second ( FEV1 ) was generally better in the treated groups than in control groups but a pooled estimate of effect was not possible .
Resistance to antibiotic increased more in the antibiotic treated group than in placebo group .
REVIEW ER 'S CONCLUSIONS Nebulised anti-pseudomonal antibiotic treatment improves lung function and reduces frequency of exacerbations of infection in people with cystic fibrosis .