***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: AIMS To examine the pharmacokinetics of ciprofloxacin and fleroxacin in plasma and sputum of patients with an acute exacerbation of chronic bronchitis or bronchiectasis following the first dose and again during the third day of treatment . METHODS Twelve patients , aged > 35 years , with acute infective exacerbation of bronchitis or bronchiectasis were allocated r and omly to treatment with either fleroxacin 400 mg daily or ciprofloxacin 500 mg twice daily in an open , parallel group design . Plasma and sputum were collected during the first and third days of treatment . The time course of concentrations in sputum was modelled assuming that it acted as a negligibly small compartment of distribution . RESULTS The mean sputum to plasma ratios of both ciprofloxacin and fleroxacin were approximately 1 on both days 1 and 3 . Peak concentrations of ciprofloxacin in sputum were achieved 1.6 ( 95 % CI on mean difference 0.8 - 2.3 ) and 1.2 ( 0.4 - 1.9 ) h later than in plasma on day 1 and day 3 , respectively ( mean difference + /- 95 % confidence interval ) . For fleroxacin , the corresponding delay in time to peak concentrations was less marked and not significant . Fleroxacin  accumulated in plasma ( accumulation index 1.52+/-0.07 ) and sputum ( accumulation index 1.79+/-0.39 ) from day 1 to day 3 . Accumulation did not occur for ciprofloxacin because the dose interval ( 12 h ) was considerable longer than its half life ( 3 - 4 h ) . CONCLUSIONS The sputum to plasma ratio of ciprofloxacin and fleroxacin is approximately 1 . The time to peak concentrations of ciprofloxacin in sputum is slightly delayed compared with plasma . Fleroxacin accumulates over time in both plasma and sputum consistent with its longer half-life In a large multinational study , the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d . followed by oral cefuroxime axetil 500 mg b.i.d . was compared to that of amoxicillin plus clavulanic acid ( CA ) administered as 1.2 g intravenously t.i.d . followed by 625 mg orally t.i.d . in the treatment of lower respiratory tract infections in hospitalised patients . A total of 512 patients were entered ( 256 in each treatment group ) . All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy . Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy . The clinical responses in the two treatment groups were very similar : 223 of 256 ( 87.1 % ) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 ( 85.9 % ) with amoxicillin/CA . Positive pre-treatment sputum sample s were obtained from 44 % of the patients . Clearance rates obtained were again similar : 72.8 % with cefuroxime/cefuroxime axetil and 70 % with amoxicillin/CA . Ten percent of the isolates were beta-lactamase producers , similar numbers of which were cleared in both groups . Both regimens were generally well tolerated , with only 5 % of patients treated with the cefuroxime regimen and 4.3 % of patients treated with amoxicillin/CA experiencing drug-related adverse events .  Cefuroxime/cefuroxime axetil “ follow-on ” therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA , with the advantage of twice daily oral administration OBJECTIVE To compare the efficacy and safety of Cefaclor AF vs Clarithromycin in the treatment of acute exacerbation of chronic bronchitis in adult subjects . PATIENTS AND METHODS This study was conducted on 300 patients suffering from acute exacerbation of chronic bronchitis , who attended the out patient clinics of ten different hospitals throughout Pakistan . Pneumonia , bronchiectasis and tuberculosis were excluded with the help of chest radiography and sputum smear examination . Pretherapy sputum culture and sensitivity ( c/s ) were tested and patients were r and omized and supplied with either tablet Cefaclor 375 mg or tablet Clarithromycin 250 mg to be taken twice daily . Patients were evaluated at day 0 and then at day 3 - 5 and day 10 - 11 . Post therapy sputum c/s was done on day 10 - 11 . A fourth and final visit was planned on day 20 - 24 which was optional . At each visit , the severity of disease and the signs and symptoms were recorded on the clinical report forms according to the preset st and ards . RESULTS Of 136 patients in the Cefaclor group and 142 patients in the Clarithromycin group , cure was achieved in 44 vs 35 subjects , improvement in 78 vs 91 subjects and failure in 16 vs 18 subjects among Cefaclor vs Clarithromycin groups respectively . The overall clinical efficacy ( cure and improvement combined ) was 88.4 % in the Cefaclor group and 87.5 % in the Clarithromycin group . Nine patients in the Cefaclor group and patients in the Clarithromycin group had one adverse event whereas twelve patients in each group had two or more adverse events . CONCLUSIONS The above results show that both Cefaclor AF and Clarithromycin are equally effective and safe in the treatment of acute exacerbation of chronic bronchitis in adult patients Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous setting s globally , high quality evidence to inform management is scarce . It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations , but not all practitioners agree . Inadequately treated exacerbations may risk lung function deterioration . Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis . Methods We are conducting a b ronchiectasis e xacerbation st udy ( BEST ) , which is a multicentre , r and omised , double-blind , double-dummy , placebo-controlled , parallel group trial , in five centres ( Brisbane , Perth , Darwin , Melbourne , Auckl and ) . In the component of BEST presented here , 189 children fulfilling inclusion criteria are r and omised ( allocation-concealed ) to receive amoxicillin-clavulanic acid ( 22.5 mg/kg twice daily ) with placebo-azithromycin ; azithromycin ( 5 mg/kg daily ) with placebo-amoxicillin-clavulanic acid ; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days . Clinical data and a paediatric cough-specific quality of life score are obtained at baseline , at the start and resolution of exacerbations , and at day 14 . In most children , blood and deep nasal swabs are also collected at the same time points . The primary outcome is the proportion of children whose exacerbations have resolved at day 14 . The main secondary outcome is the paediatric cough-specific quality of life score . Other outcomes are time to next exacerbation ; requirement for hospitalisation ; duration of exacerbation ; and spirometry data . Descriptive viral and bacteriological data from nasal sample s and blood markers will also be reported . Discussion Effective , evidence -based management of exacerbations in people with bronchiectasis is clinical ly important . Yet , there are few r and omised controlled trials ( RCTs ) in the neglected area of non-cystic fibrosis bronchiectasis . Indeed , no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist . Our multicentre , double-blind RCT is design ed to determine if azithromycin and amoxicillin-clavulanic acid , compared with placebo , improve symptom resolution on day 14 in children with acute respiratory exacerbations . Our planned assessment of the predictors of antibiotic response , the role of antibiotic-resistant respiratory pathogens , and whether early treatment with antibiotics affects duration and time to the next exacerbation , are also all novel . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) number ACTRN12612000011886 Background Bronchiectasis unrelated to cystic fibrosis ( CF ) is being increasingly recognized in children and adults globally , both in re source -poor and in affluent countries . However , high- quality evidence to inform management is scarce . Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations , because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis . Azithromycin has a prolonged half-life , and with its unique anti-bacterial , immunomodulatory , and anti-inflammatory properties , presents an attractive alternative . Our proposed study will test the hypothesis that oral azithromycin is non-inferior ( within a 20 % margin ) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis . Methods This will be a multicenter , r and omized , double-blind , double-dummy , placebo-controlled , parallel group trial involving six Australian and New Zeal and centers . In total , 170 eligible children will be stratified by site and bronchiectasis etiology , and r and omized ( allocation concealed ) to receive : 1 ) azithromycin ( 5 mg/kg daily ) with placebo amoxycillin-clavulanate or 2 ) amoxycillin-clavulanate ( 22.5 mg/kg twice daily ) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations . Clinical data and a parent-proxy cough-specific quality of life ( PC-QOL ) score will be obtained at baseline , at the start and resolution of exacerbations , and on day 21 . In most children , blood and deep-nasal swabs will also be collected at the same time points . The primary outcome is the proportion of children whose exacerbations have resolved at day 21 . The main secondary outcome is the PC-QOL score . Other outcomes are : time to next exacerbation ; requirement for hospitalization ; duration of exacerbation , and spirometry data . Descriptive viral and bacteriological data from nasal sample s and blood inflammatory markers will be reported where available . Discussion Currently , there are no published r and omized controlled trials ( RCT ) to underpin effective , evidence -based management of acute respiratory exacerbations in children with non-CF bronchiectasis . To help address this information gap , we are conducting two RCTs . The first ( b ronchiectasis e xacerbation st udy ; BEST-1 ) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo , and the second RCT ( BEST-2 ) , described here , is design ed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) number http://ACTRN12612000010897 . Background Clinical management of primary ciliary dyskinesia ( PCD ) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections , through the administration of antibiotics . Treatment practice s in PCD are largely extrapolated from more common chronic respiratory disorders , particularly cystic fibrosis , but no r and omized controlled trials ( RCT ) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD . Maintenance therapy , with the macrolide antibiotic azithromycin , is currently widely used in chronic respiratory diseases including PCD . In addition to its antibacterial properties , azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties . The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD . The secondary objectives are to evaluate the efficacy of azithromycin on lung function , ventilation inhomogeneity , hearing impairment , and symptoms ( respiratory , sinus , ears and hearing ) measured on a PCD-specific health-related quality of life instrument , and to assess the safety of azithromycin  maintenance therapy in PCD . Methods The BESTCILIA trial is a European multi-centre , double-blind , r and omized , placebo-controlled , parallel group study . The intervention is tablets of azithromycin 250/ 
    Output:
    
Limited low- quality evidence favours short-term oral fluoroquinolones over beta-lactam antibiotics for patients hospitalised with exacerbations .
Very low- quality evidence suggests no benefit from inhaled aminoglycosides verus polymyxins .