***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 Purpose To assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis ( CF ) aged ≥6 years with chronic Pseudomonas aeruginosa lung infection . Study design and methods A prospect i ve , central ly r and omised , phase III , open-label study in patients with stable CF aged ≥6 years with chronic P aeruginosa lung infection . Patients were r and omised to Colobreathe dry powder for inhalation ( CDPI , one capsule containing colistimethate sodium 1 662 500 IU , twice daily ) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution ( TIS ) . Study duration was 24 weeks . Results 380 patients were r and omised . After logarithmic transformation of data due to a non-normal distribution , adjusted mean difference between treatment groups ( CDPI vs TIS ) in change in forced expiratory volume in 1 s ( FEV1 % predicted ) at week 24 was −0.98 % ( 95 % CI −2.74 % to 0.86 % ) in the intention-to-treat population ( n=373 ) and −0.56 % ( 95 % CI −2.71 % to 1.70 % ) in the per protocol population ( n=261 ) . The proportion of colistin-resistant isolates in both groups was ≤1.1 % . The number of adverse events was similar in both groups . Significantly more patients receiving CDPI rated their device as ‘ very easy or easy to use ’ ( 90.7 % vs 53.9 % respectively ; p<0.001 ) . Conclusion CDPI  demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment . There was no emergence of resistance of P aeruginosa to colistin . Overall , CDPI was well tolerated . Trial Reg No EudraCT 2004 - 003675 - 36 OBJECTIVES To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis ( CF ) , rather than st and ard therapy , was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions . STUDY DESIGN Costs were assessed in a r and omized controlled trial conducted in Australia and New Zeal and on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or st and ard therapy until they reached 5 years of age . A health care funder perspective was adopted . Re source use measurement was based on st and ardized data collection forms administered for patients across all sites . Unit costs were obtained primarily from government schedules . RESULTS Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in st and ard therapy group ( mean difference AUD1902 , 95 % CI AUD-27 782 to 31 586 , P = .90 ) . Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the st and ard therapy group ( mean difference AUD-9288 ; 95 % CI AUD-35 252 to 16 676 , P = .48 ) . CONCLUSIONS BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a st and ard protocol based upon clinical features and oropharyngeal culture results alone . Following on our previous findings that BAL-directed treatment offers no clinical advantage over st and ard therapy at age 5 years , flexible bronchoscopy with BAL can not be recommended for the routine management of preschool children with CF on the basis of overall cost savings 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 Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis ( CF ) is currently treated with intensive antibiotic therapy . At this stage , inflammation and tissue injury might have already occurred . Moreover , bacterial eradication is not always achieved . Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies . A study was undertaken to establish prospect ively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF . Methods This 3-year triple-blind r and omised controlled trial included 65 children with CF without P aeruginosa infection . Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls . The primary outcome was P aeruginosa infection . Secondary outcomes were serum anti-Pseudomonas antibodies , pulmonary function , exacerbations , chest x-ray scores , inflammation parameters , respiratory pathogens and antimicrobial resistance . Results There was no difference in acquisition of P aeruginosa infection between the control and treatment groups ( annual incidence 14 % vs 11 % ; HR 0.738 , 95 % CI 0.299 to 1.822 ) . Anti-Pseudomonas antibodies emerged earlier in the control group , but this difference had disappeared after 3 years . Chronic infection was observed in 19 % of controls and 12 % of treated patients . Decline in pulmonary function and other clinical outcomes did not differ between the two groups . In the treatment group , significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria . Conclusions Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages . Shifts in bacterial colonisation dem and caution . Trial Registration Number IS RCT N 11604593 Rationale In cystic fibrosis ( CF ) , the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa . Pathogens subsequently descend to the lower airways , with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease . Unlike conventional aerosols , vibrating aerosols applied with the PARI Sinus ™ nebulizer deposit drugs into the paranasal sinuses . This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage . Objectives To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage ; and on patient quality of life , measured with the Sino-Nasal Outcome Test ( SNOT-20 ) , and otologic and renal safety and tolerability . Methods Patients were r and omized to inhalation of tobramycin ( 80 mg/2 mL ) or placebo ( 2 mL isotonic saline ) once daily ( 4 minutes/nostril ) with the PARI Sinus ™ nebulizer over 28 days , with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days . Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline . Results Nine patients participated , six initially receiving tobramycin and three  placebo . Sinonasal inhalation was well tolerated , with serum  tobramycin < 0.5 mg/L and stable creatinine . P. aeruginosa quantity decreased in four of six ( 67 % ) patients given tobramycin , compared with zero of three given placebo ( non-significant ) . SNOT-20 scores were significantly lower in the tobramycin than in the placebo group ( P=0.033 ) . Conclusion Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF 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 BACKGROUND A light-porous-particle , dry-powder formulation of tobramycin was developed , using PulmoSphere ® technology , to improve airway delivery efficiency , substantially reduce delivery time , and improve patient convenience and satisfaction . We evaluated the safety , efficacy and convenience of tobramycin inhalation powder ( TIP ™ ) versus tobramycin inhalation solution ( TIS , TOBI ® ) for treating Pseudomonas aeruginosa infection in cystic fibrosis ( CF ) patients aged ≥6 years . METHODS In this open-label study , 553 patients were r and omized 3:2 to TIP  ( total 112 mg tobramycin ) via the Novartis T-326 Inhaler or TIS 300mg/5mL via PARI LC ® PLUS nebulizer twice daily for three treatment cycles ( 28 days on-drug , 28 days off-drug ) . Safety , efficacy , and treatment satisfaction outcomes were evaluated . RESULTS TIP was generally well-tolerated ; adverse events were similar in both groups . The rate of cough suspected to be study drug related was higher in TIP-treated patients ( TIP : 25.3 % ; TIS : 4.3 % ) , as was the overall discontinuation rate ( TIP : 26.9 % ; TIS : 18.2 % ) . Increases in FEV(1)% predicted from baseline to Day 28 of Cycle 3 were similar between groups ; the mean reduction in sputum P. aer 
    Output:
    
Tinnitus and voice alteration were the only adverse events significantly more common in the inhaled antibiotics group .
No significant differences were found in the remaining comparisons with regard to lung function .
Inhaled anti-pseudomonal antibiotic treatment probably improves lung function and reduces exacerbation rate , but pooled estimates of the level of benefit were very limited .
The best evidence is for inhaled tobramycin .