***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: 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 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 ) During a 22-month period 35 children with cystic fibrosis received 52 courses of antibiotic therapy for acute pulmonary exacerbations , including 26 cases of therapy with piperacillin and 26 courses with ticarcillin plus tobramycin .  Groups were similar in age ( 5 vs. 5.4 years ) , disease severity based on Schwachman scores and presenting symptoms . Pseudomonas aeruginosa was the most common organism isolated in 90 % of sputum cultures . Mean minimal inhibitory concentrations for  piperacillin , ticarcillin and tobramycin were 8 , 64 and 1 microgram/ml , respectively . Piperacillin pharmacokinetic data revealed an average half-life in serum of 36 minutes . Peak serum concentrations averaged 144 micrograms/ml , and after 4 hours serum concentrations continued to exceed the P. aeruginosa 90 % minimal inhibitory concentration in 50 % of children . The dosage requirement for tobramycin was quite variable , necessitated monitoring of aminoglycoside serum concentrations and in most cases result ed in at least one dosage adjustment . Emergence of resistant bacteria was not seen in 26 courses of piperacillin therapy . Both regimens were effective and well-tolerated . Single agent therapy has the advantage of providing reliable serum concentrations and , in contrast to the st and ard therapy , does not necessitate monitoring of serum drug concentrations BACKGROUND Although anti-pseudomonal antibiotics are routinely used in the treatment of acute respiratory exacerbations of adult cystic fibrosis ( CF ) , the specific efficacy of such treatment remains uncertain , the mechanism of action of these agents is not fully understood , and the role of sputum susceptibility testing in clinical decision making is controversial . AIMS We investigated the relationship between susceptibility testing and clinical outcome in adult CF patients colonised with Pseudomonas aeruginosa . METHODS Sputum sample s were collected before , during and after respiratory exacerbations from 31 admissions ( 17 patients ) .  Sputum colony counts and MIC of P. aeruginosa were performed . RESULTS Sputum colony counts did not change significantly during or after intravenous ( IV ) antibiotic therapy . Clinical outcome parameters ( lung function , 12-minute walking distance , sputum weight and quality of life ) were compared with susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics used , and no correlation was evident . There was no evidence for the development of cross-resistance and there was no change in the proportion of mucoid colonies with therapy . CONCLUSIONS While this study has a small patient sample size , it highlights the inconsistency of the role of antipseudomonal drugs also shown in other similar studies . The presence of P. aeruginosa in sputum of acutely ill CF patients prompts us to prescribe i.v . antipseudomonal drugs . If this approach was valid , we would expect to find a reduction in sputum colony counts and improvement in clinical parameters with the use of antibiotics to which the organisms were sensitive . The fact that such a relationship can not be consistently demonstrated in this and other studies suggests that the use of antipseudomonal therapy in these patients requires more critical bacteriological and clinical evaluation 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 20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a r and omized cross-over study comparing ceftazidime ( 150 mg/kg body weight/24 h ) plus tobramycin ( 10 mg/kg body weight/24 h ) to ceftazidime alone ( 150 mg/kg body weight/24 h ) , both given intravenously for 2 weeks . 17 patients completed the study ; both treatment regimens improved lung function and decreased the WBC count . No difference in clinical efficacy was found between the treatments . Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments . No changes were seen in minimal inhibitory concentrations during treatment . None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated . Seventy-one percent of patients treated with ticarcillin alone responded favorably . The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone . Severity of the underlying disease was the most important determinant of response to treatment . Ticarcillin-resistant organisms were recovered during treatment in 50 % of patients who received this drug ; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clin 
    Output:
    
The meta- analysis did not demonstrate any significant differences between monotherapy and combination therapy , in terms of lung function ; symptom scores ; adverse effects ; and bacteriological outcome measures .