***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: BACKGROUND : There is evidence that administration of higher doses of aminoglycosides given less frequently improves the bactericidal effect and reduces the potential to cause side effects . To investigate this , a prospect ively r and omised open label therapeutic trial was undertaken in stratified groups of patients with cystic fibrosis to examine the efficacy and toxic potential of an aminoglycoside dosing regimen design ed to generate high peak drug concentrations at 12 hourly intervals compared with conventional dosing at eight hourly intervals . METHODS : Patients in group A received tobramycin eight hourly using a dose aim ed at generating a peak concentration of 10 mg/l with trough concentrations below 2 mg/l , and those in group B received the total daily dose required to achieve eight hourly target concentrations administered as two equal 12 hourly doses . Clinical outcomes measured and assessed included vestibular symptoms , hearing and renal function , length of hospital stay , readmission rate , and mortality . RESULTS : Twenty nine patients were recruited during a six month period , 20 to group A and nine to group B. The average peak tobramycin level was higher in group B ( 12.5 ( 2.2 ) mg/l ) than in group A ( 7.9 ( 1.9 ) mg/l ) , whilst the average trough level was higher in group A ( 0.8 ( 0.3 ) mg/l ) than in group B ( 0.5 ( 0.2 ) mg/l ) . There was a difference in the number of ototoxic events between patients in group A ( seven of 18 , 38.9 % ) and group B ( none of eight ) , but no difference was found in other outcome measures assessed . CONCLUSIONS : These results suggest that 12 hourly high peak aminoglycoside dosing may be less toxic than equivalent eight hourly dosing , without any apparent difference in efficacy OBJECTIVES Once-daily administration of aminoglycosides in cystic fibrosis ( CF ) patients is considered equally efficacious and potentially less nephrotoxic than dosing three times a day . However , the choice of the most suitable PK/PD index ( C(max)/MIC versus AUC(24)/MIC ) to ensure optimum clinical outcome in this patient population is not clear . PATIENTS AND METHODS In a single-centre , open , r and omized , controlled , non-blinded study 33 adult CF patients ( 20 females , 19 - 37 years ) were treated with intravenous tobramycin ( 10 mg/kg/day ) for 14 days given either as single dose once a day ( Q24 ; 17 patients ) or divided into three equal doses every 8 h ( Q8 ; 16 patients ) . Tobramycin serum concentrations and MICs for Pseudomonas aeruginosa were determined on days 1 and 14 . The clinical outcome parameter , correlated to PK/PD indices , was the percentage predicted forced expiratory volume in 1 s ( FEV(1)% pred . ) . RESULTS FEV(1)% pred . improved significantly for both treatments . There was a log-linear relationship between C(max)/MIC and FEV(1)% pred . and AUC/MIC and FEV(1)% pred . for both treatments . For equal values of AUC24/MIC , however , Q24 treatment provided better improvement in lung function than Q8 dosing , whereas C(max)/MIC did not show any dosing interval dependence . A statistically significant increase was observed for MIC ( day 1 ) versus MIC ( day 14 ) for Q24 treatment , however , no such difference was observed for Q8 treatment . CONCLUSIONS The most important PK/PD parameter for clinical outcome in CF patients was C(max)/MIC . Outcome prediction of AUC(24)/MIC was dependent on the regimen . The increase of P. aeruginosa resistance after once-daily administration is linked to a long dosing interval . More and larger studies are needed to optimize the dosing regimen for maximum clinical outcome with minimum resistance development Twenty-six patients with cystic fibrosis and pulmonary exacerbations were enrolled in a prospect i ve r and omized study to compare the efficacy of aminoglycosides ( tobramycin or netilmicin ) administered once daily ( 21 episodes , 5 with netilmicin , 16 with tobramycin ) and thrice daily ( 23 episodes , 2 with netilmicin , 21 with tobramycin ) , respectively . In addition , the patients received an anti-pseudomonal beta-lactam antibiotic . In the single-dose group the total daily dosage was 4.97 + /- 1.12 mg/kg ( total dosage per exacerbation : 74.55 mg/kg ) , compared to 9.60 + /- 2.70 mg/kg in the triple-dose group ( total dosage per exacerbation : 165.12 mg/kg ) . The mean peak and trough serum levels of the aminoglycoside were 8.31 + /- 1.76 mg/l and 0.18 + /- 0.10 mg/l , respectively in the single dose group compared to 6.12 + /- 1.30 mg/l and 0.58 + /- 0.31 mg/l in the triple dose group . Success of treatment , defined as decrease in leucocyte counts , normalization of elevated CRP-values , number of days in hospital and interval until next admission to hospital , was not different between both groups . We conclude that single daily dose of aminoglycosides was as efficacious as triple dose in our patients 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 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms ( > 20 mg/L ) and AUC(24 ) values at the upper end of the desired range ( 70 - 100 mg.h/L ) ABSTRACT We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large r and omized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis ( the TOPIC study ) . All patients were eligible to have st and ard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz .  High-frequency pure tone audiometry  over 10 to 16 kHz was also performed with a subset of patients . Audiometry was undertaken at the start of tobramycin treatment , at the end of a 14-day course of treatment , and at follow-up 6 to 8 weeks later . We enrolled 244 patients , of whom 219 ( 125 children and 94 adults ) completed treatment . Nineteen patients were excluded from analysis due to abnormal baseline audiometry . Complete pre- and posttreatment st and ard audiological data were obtained for 168/219 patients . We found no significant differences in hearing thresholds when they were assessed at the baseline , at the end of treatment , and at follow-up 6 to 8 weeks later were compared . In addition , no significant differences in hearing thresholds were detected between treatment regimens . Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry . We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit , no measurable effect on hearing was apparent with either once- or three-times-daily treatment . Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy , as evidence d by the patients excluded from this study due to hearing loss , also requires further characterization Our objective was to compare the efficacy , safety , and microbiology of once-daily intravenous ( IV ) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa ( PA ) pulmonary exacerbations in cystic fibrosis ( CF ) . CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin ( Mono ) or conventional therapy with tobramycin/ceftazidime given 8-hourly ( Conv ) . The two longitudinal groups received therapy in a double-blind , r and omized manner over a period of 2 years . Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups . Results were assessed for both short-term changes ( efficacy and safety after 10 days of IV antibiotics during acute exacerbations ) and long-term changes ( efficacy , safety , and sputum microbiology between study entry and exit ) . Pulmonary function tests ( PFTs ) on admission were similar in both groups . After 10 days of IV antibiotics , absolute mean improvements in percent of predicted PFTs were 12.8 , 12.1 , and 13.7 for forced expiratory volume in 1 sec ( FEV(1 ) ) , forced vital capacity ( FVC ) , and forced expired flow between 25 - -75 % of FVC ( FEF(25 - -75 % ) ) in the Conv group ( n = 51 admissions ) compared to 10.6 , 9.9 , and 10.6 in the Mono group ( n = 47)(P<0.05 for all ) . Sixteen percent in the Conv group and 15 % of patients in the Mono group did not respond to therapy by day 10 . Long-term PFT patterns were similar for the Conv and Mono groups . The time between admissions did not differ . The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations ( MICs ) against PA from study entry to study exit ( P = 0.02 , n = 27 strains ) ; this failed to reach significance in the Conv group ( P = 0.08 , n = 25 ) . There was no significant increase in the number of isolates , with MIC > or = 8 mg/L in both groups . No short- or long-term changes in audiology or serum creatinine were found in either group . After 10 days of IV therapy , the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups ( P0.05 ) . This increase was greater in the Conv compared to the Mono group ( P < 0.05 ) . We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy . Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy . Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation , including the impact on susceptibility of PA to tobramycin The efficacy and toxicity of a shortened tobramycin dosing interval in the treatment of exacerbations of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis patients were evaluated prospect ively . Patients ages 13 to 30 years received 34 treatment courses and were r and omized by pairs to receive tobramycin administered either every 6 or 8 hours . Peak serum concentrations were adjusted to 8 to 10 micrograms/ml ; thus a larger total daily dosage was administered to patients receiving tobramycin every 6 hours . The shorter dosing interval was associated with better pulmonary function at follow-up and significantly longer time before next hospital admission for a pulmonary exacerbation . During the study hospitalization there were no differences in pulmonary function tests , clinical score , sputum carriage of P. aeruginosa , toxicity or necessary length of hospitalization . A 6-hour tobramycin dosing interval was more efficacious than an 8-hour dosing interval in the treatment of cystic fibrosis patients Although there are reports of cases of acute renal failure occurring in cystic fibrosis ( CF ) patients , usually in association with the use of nephrotoxic antibiotic therapy , there have been no studies of renal function in this patient group . We hypothesized that long-term use of intravenous ( IV ) nephrotoxic antibiotics ( aminoglycosides and colistin sulphomethate ) may contribute to renal disease in CF patients . In a prospect i ve study , we assessed creatinine clearance as an index 
    Output:
    
Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis .
There is evidence of less nephrotoxicity in children