***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: ABSTRACT The present multicenter , r and omized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis . Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime ( 200 mg/kg of body weight/day ) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion . The primary endpoint was the variation in the forced expiratory volume in 1 s ( FEV1 ) during the course of antibiotic treatment . Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment . The improvement in FEV1 at the end of therapy was not statistically different between the two treatment procedures ( + 7.6 % after continuous infusion and + 5.5 % after short infusions ) but was better after continuous ceftazidime treatment in patients harboring resistant isolates ( P < 0.05 ) . The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime ( P = 0.04 ) . The mean serum ceftazidime concentration during the continuous infusion was 56.2 ± 23.2 μg/ml ; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 μg/ml , respectively . The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens . Quality -of-life scores were similar whatever the treatment procedure , but 82 % of the patients preferred the continuous-infusion regimen . Adverse events were not significantly different between the two regimens . In conclusion , the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole , but it gave better results in patients harboring resistant isolates of P. aeruginosa The steady state pharmacokinetic properties of ciprofloxacin and ofloxacin were compared in cystic fibrosis patients . In a cross-over study eighteen adult patients with chronic Pseudomonas aeruginosa lung infection were given either oral ciprofloxacin 750 mg bid or oral ofloxacin 400 mg bid for two weeks . Three months later the alternative treatment was given . Concentrations were determined by a microbiological assay . Mean serum concentrations of ofloxacin ( peak 5.9 mg/l ) were higher than for ciprofloxacin ( peak 4.0 mg/l ) . The time to reach maximal concentrations did not differ . The apparent total body clearance was significantly greater for ciprofloxacin , but renal clearances were similar . Relative to ofloxacin ciprofloxacin had a significantly shorter serum elimination half-life ( 3.4 vs. 6.4 h ) , showed less penetration into sputum ( 18 % vs. 79 % ) and a lesser amount was recovered in urine ( 21 % vs. 71 % up to 12 h after dosing ) . No correlation was found between any pharmacokinetic parameter and change in pulmonary function BACKGROUND Intravenous tobramycin ( three-times daily ) is widely used for pulmonary exacerbations in patients with cystic fibrosis who have chronic Pseudomonas aeruginosa infection . We undertook a double-blind , r and omised controlled trial to assess the safety and efficacy of once versus three-times daily tobramycin in these patients . METHODS 244 patients from 21 cystic-fibrosis centres in the UK were r and omly assigned to once or three-times daily tobramycin ( with ceftazidime ) for 14 days . Treatment was given as 30-min infusions of tobramycin in 0.9 % saline . Primary outcome measure was change in forced expiratory volume in 1s ( FEV1 ) , over the 14 days of treatment , expressed as a percentage of the predicted normal value for age , sex , and height . We also measured the change in FEV1 expressed as a percentage of baseline . Secondary outcomes included change in serum creatinine . The study was powered for equivalence , and primary analysis was per protocol . FINDINGS 219 patients ( 107 once daily , 112 three-times daily ) completed the study per protocol . None was lost to follow-up , although 20 discontinued intervention . Of 122 patients assigned to once daily treatment , three did not receive the study regimen . The mean change in FEV1 ( % predicted ) over 14 days was similar on the two regimens ( 10.4 % [ once daily ] vs 10.0 % [ three-times daily ] ; adjusted mean difference 0.4 % [ 95 % CI -3.3 to 4.1 ] ) . Mean% change in FEV1 from baseline was also similar in both treatments ( 21.9 % vs 22.1 % ; -0.1 % [ -8.0 to 7.9 ] ) . There was no significant difference in% change in creatinine from baseline ( -1.5 % [ once daily ] vs 1.7 % [ three-times daily ] ) . However , in children , once daily treatment was significantly less nephrotoxic than was thrice daily ( mean% change in creatine -4.5 % [ once daily ] vs 3.7 % [ thrice daily ] ; adjusted mean difference -8.0 % , 95 % CI -15.7 to -0.4 ) . No patients developed hearing loss during the study , although two reported acute dizziness and were withdrawn from the study . INTERPRETATION Intravenous tobramycin has equal efficacy if given once or three-times daily ( with ceftazidime ) for pulmonary exacerbations of cystic fibrosis . The once daily regimen might be less nephrotoxic in children Purpose : We hypothesized that a single intravenous ( iv ) tobramycine infusion ( treatment B ) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa ( PA ) infection in cystic fibrosis ( CF ) as the commonly performed treatment of three doses ( treatment A ) . Toxicity and practicability may even be improved in the single-dose regimen . Methods : This was a r and omized crossover study comparing outcome after 14 and 35 days . The primary end-point was a decrease in the leukocyte count , and the secondary end-points were clinical and lung function parameters , Pseudomonas quantification in sputum , and inflammation markers ( immunoglobulin G , C-reactive protein ) in serum . 30 patients ( 20 female , mean age 11.2 years , mean age range 1.7–18.1 years ) received elective 14-day courses of treatments A or B , followed by the alternative treatment after a mean interval of 37 ( ± 21 ) weeks . Results : With the exception of PA density , there were no significant differences between both treatment strategies after 14 days of treatment . After 35 days of treatment , there were no significant changes in the leukocyte count and inflammation markers . Both treatment strategies reduced the bacterial load in the airways , as reflected by a decreased PA density in sputum . Nephrotoxicity was equal in both groups , with a transient slight elevation of urinary N-acetyl-β-glucosaminidase concentrations . St and ard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy . Mean body weight increased during the study period by 0.5 kg . Forced expiratory volume increased by approximately 5 % of the predicted volume , forced vital capacity increased by 2 % of predicted capacity , and forced mid expiratory flow rate increased by 7 % ( A ) or 4 % ( B ) of the predicted normal value , although these changes were not statistically significant . Conclusion : We conclude that tobramycin given in a daily single dose ( with the advantage of being more practical in a home environment ) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinical ly stable patients with CF Ceftazidime was administered to 41 patients with serious infections caused by Pseudomonas aeruginosa ( 24 cases ) and other bacteria ( 17 cases ) . The clinical response rate of pseudomonas infections ( 88 % ) was similar to that of other bacteria ( 94 % ) with microbiological eradication of 83 % of initial pseudomonas isolates compared to 82 % of non-pseudomonas strains . The development of resistance to ceftazidime  during therapy was observed in 3 cases ( Enterobacter agglomerans , Enterobacter cloacae , and Ps . aeruginosa ) , and superinfection by a resistant Enterobacter agglomerans occurred in one case . Adverse reactions of clinical significance included two cases of leukopenia and one case each of azotaemia , diarrhoea ( Clostridium difficile toxin positive ) , and rash A r and omised controlled open comparison of azlocillin and gentamicin versus carbenicillin and gentamicin was carried out in patients with cystic fibrosis who were chronically infected with Pseudomonas aeruginosa . The clinical response was assessed by measurements of pulmonary function and of the patients ' feelings of wellbeing scored on a visual analogue scale . The sputum penetration of the antibiotics used was also studied . The two groups of 10 patients were similar in terms of age , sex , and pulmonary function at entry to the trial . Both regimens produced significant improvement in pulmonary function over 10 days . The mean FEV1 in the azlocillin group increased from 1206 to 1760 ml ( p less than 0.001 ) . In the carbenicillin group the mean FEV1 increased from 1116 to 1619 ml ( p less than 0.001 ) . Significant improvements in peak expiratory flow rate , forced vital capacity , and score on the visual analogue scale were also seen but there was no significant difference between the antibiotic regimens . Despite high serum concentrations the sputum penetration of the antibiotics was poor Background Newborn screening allows novel treatments for cystic fibrosis ( CF ) to be trialled in early childhood before irreversible lung injury occurs . As respiratory exacerbations are a potential trial outcome variable , we determined their rate , duration and clinical features in preschool children with CF ; and whether they were associated with growth , lung structure and function at age 5 years . Methods Respiratory exacerbations were recorded prospect ively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years , when all participants underwent clinical assessment , chest CT scans and spirometry . Results 168 children ( 88 boys ) experienced 2080  exacerbations , at an average rate of 3.66 exacerbations per person-year ; 80.1 % were community managed and 19.9 % required hospital admission . There was an average increase in exacerbation rate of 9 % ( 95 % CI 4 % to 14 % ; p<0.001 ) per year of age . Exacerbation rate differed by site ( p<0.001 ) and was 26 % lower ( 95 % CI 12 % to 38 % ) in children receiving 12 months of prophylactic antibiotics . The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores . Ever having a hospital-managed exacerbation was associated with bronchiectasis ( OR 2.67 , 95 % CI 1.13 to 6.31 ) in chest CT scans , and lower weight z scores at 5 years of age ( coefficient −0.39 , 95 % CI −0.74 to −0.05 ) . Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group BACKGROUND A previous retrospective study suggested that a policy of regular anti-pseudomonal antibiotic treatment improved pulmonary function and increased survival in patients with cystic fibrosis chronically infected with Pseudomonas species . The results of a prospect i ve multicentre study to compare the effects on pulmonary function and mortality of three monthly elective anti-pseudomonal antibiotic treatment with conventional symptomatic treatment are reported . METHODS Sixty patients with cystic fibrosis , chronically infected with P aeruginosa , were r and omised to the two treatment arms ( elective or symptomatic ) and followed clinical ly at yearly review s. The major end points were changes in forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) . Survival was a secondary end point . RESULTS Patients in the symptomatic group received a mean of three antibiotic treatments each year and those in the elective group received four antibiotic treatments during each year of the study . No significant differences in FEV1 and FVC were found between the two groups after three years . There was a statistically non-significant higher rate of deaths in the elective group ( n = 4 ) , three of which were associated withB cepacia infection , compared with the symptomatic group ( n = 0 ) . CONCLUSIONS This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonasspecies Piperacillin was evaluated as an antipseudomonas antibiotic in a double-blind controlled trial involving 18 pulmonary exacerbations of cystic fibrosis .  St and ard antibiotic treatment ( flucloxacillin plus tobramycin ) was compared with st and ard treatment plus intravenous piperacillin 
    Output:
    
The quality of the included studies was largely poor and , with a few exceptions , these comprised of mainly small , inadequately reported studies .When comparing treatment with a single antibiotic to a combined antibiotic regimen , those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function , but with very low quality evidence .
When limited to the four  placebo-controlled  studies ( n = 214 ) , no difference was observed , again with very low quality evidence .
With regard to the review 's remaining primary outcomes , there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life .
There were no effects on the secondary outcomes weight or adverse effects .
When comparing specific antibiotic combinations there were no significant differences between groups on any measure .
In the comparisons between intravenous and nebulised antibiotic or oral antibiotic ( low quality evidence ) , there were no significant differences between groups on any measure .
No specific antibiotic combination can be considered to be superior to any other , and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes .