***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 
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    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 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 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 To evaluate whether the addition of an aminoglycoside might enhance the clinical efficacy of ceftazidime in cystic fibrosis patients with acute exacerbations of chronic Pseudomonas lung infections we carried out a prospect i ve , comparative , r and omized blind study with three schedules : ceftazidime vs. ceftazidime plus sisomicin ( C/S ) vs. piperacillin plus sisomicin , for a total of 60 courses of 14 days of treatment . Each treatment led to clinical and radiologic improvement with marked reduction of signs of acute infection . Statistically there was no significant difference in clinical responses among the schedules . No side effect appeared during treatments with ceftazidime or C/S. Hyperpyrexia was seen in 35 % of patients receiving piperacillin . Decrease in Pseudomonas aeruginosa count to less than 10(5 ) colony-forming units/ml of sputum was achieved in 60 % of patients treated with C/S and in 30 % of patients who received ceftazidime or piperacillin plus sisomicin ( statistically not significant ) . A transient increase in mean geometric minimal inhibitory concentrations for ceftazidime and piperacillin was observed at the end of the combined therapies . A larger percentage of persistent resistant strains of P. aeruginosa was seen after the combined therapies . We conclude that ceftazidime as monotherapy may be an effective alternative in Pseudomonas lung infections in cystic fibrosis patients . Its clinical efficacy seems not to be enhanced by the addition of an aminoglycoside , although reduction of Pseudomonas in the sputum was better achieved by the combination of Thirteen patients with cystic fibrosis ( aged 11 to 32 years ) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic ( 14 days , n = 8) or placebo ( 14 days , n = 4 ; 7 days , n = 1 ) . Tc-99 m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy , on the day before antibiotic or placebo , and on the day after completion of antibiotic or placebo therapy . Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol . Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone . Sixty-two percent showed further improvement after antibiotic or placebo was added ; this improvement was independent of whether antibiotic or placebo was administered ( P > 0.1 ) . These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis . Sixty adult patients with an acute respiratory exacerbation were r and omized to receive either 10 mg·kg−1 tobramycin once-daily or 3.3 mg·kg−1 tobramycin thrice-daily . Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing . Both groups showed a significant increase in respiratory function without a clinical ly significant change in renal function . For changes in forced vital capacity % predicted and serum potassium and magnesium levels , equivalence was demonstrated . For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels , there was insufficient power to demonstrate equivalence . One patient in each group showed bilateral impairment in pure tone audiogram after treatment . This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing . Equivalence between the two regimens was shown for some , but not all primary endpoints . Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results ABSTRACT Linezolid is a treatment option for  methicillin-resistant Staphylococcus aureus ( MRSA ) infections in cystic fibrosis ( CF ) patients . Little is known , however , about its pharmacokinetics in this population . Eight adults with CF were r and omized to receive intravenous ( i.v . ) and oral linezolid at 600 mg twice daily for 9 doses in a crossover design with a 9-day washout . Plasma sample s were collected after the first and ninth doses of each phase . Population pharmacokinetic analyses were performed by nonlinear mixed-effects modeling using a previously described 2-compartment model with time-dependent clearance inhibition . Monte Carlo simulation was performed to assess the activities of the linezolid dosing regimens against 42 contemporary MRSA isolates recovered from CF patients . The following pharmacokinetic parameter estimates were observed for the population : absorption rate constant , 1.91 h−1 ; clearance , 9.54 liters/h ; volume of central compartment , 26.8 liters ; volume of peripheral compartment , 17.3 liters ; and intercompartmental clearance , 104 liters/h . Linezolid  demonstrated nonlinear clearance after 9 doses , which was reduced by a mean of 38.9 % ( range , 28.8 to 59.9 % ) . Mean bioavailability was 85 % ( range , 47 to 131 % ) . At steady state , 600 mg given twice daily produced 93.0 % and 87.2 % probabilities of obtaining the target pharmacodynamic exposure against the MRSA isolates for the i.v . and oral formulations , respectively . Thrice-daily dosing increased the probabilities to 97.0 % and 95.6 % , respectively . Linezolid pharmacokinetics in these adults with CF were well described by a 2-compartment model with time-dependent clearance inhibition . St and ard i.v . and oral dosing regimens should be sufficient to reliably attain pharmacodynamic targets against most MRSA isolates ; however , more frequent dosing may be required for isolates with MICs of ≥2 μg/ml Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance . Preliminary evidence from r and omized controlled trials in patients with cystic fibrosis ( CF ) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing . The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described . In this study we compare the distribution and elimination patterns of traditional dosing ( 3.3 mg/kg q8h ) versus once-daily dosing ( 10 mg/kg q24h ) of tobramycin in six adult patients with CF . The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model . No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted . The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected . The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing , to ensure completion of the distribution phase . Our data indicate that a dose of  
    Output:
    
There was a wide variation in the individual antibiotics used in each trial .