***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: The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis . Two r and omized prospect i ve studies were performed in Northern Tanzania . In study 1 , ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days . Counts of colony-forming units ( cfu ) of Mycobacterium tuberculosis in early morning sputum were performed . In study 2 , twenty patients received either a st and ard regimen of rifampin ( R ) , isoniazid ( H ) , pyrazinamide ( Z ) , and ethambutol ( E ) ( regimen HRZE ) or a trial regimen of ciprofloxacin ( C ) , isoniazid ( H ) , and rifampin ( R ) ( regimen HRC ) . Sputum colony counts were performed for 8 wk . Patients were tested for antibodies to human immunodeficiency virus (HIV)-1 . The results demonstrate that ciprofloxacin alone has useful early bactericidal activity , result ing in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid . When HRZE and HRC regimens were compared , the HRC regimen appeared to be inferior in its sterilizing ability , with a culture conversion rate of 67 % at 2 months compared with 100 % for HRZE . The difference in outcome was most marked in HIV-1 positive patients . The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent Previously untreated patients with smear-positive pulmonary tuberculosis were r and omly allocated to treatment with 600 , 300 , 150 or 75 mg doses of rifabutin ( LM427 , ansamycin ) , 600 , 300 or 150 mg of rifampicin , 300 mg isoniazid or to no drug daily for 2 days . The fall in viable counts of Mycobacterium tuberculosis in sputum collection s during the 2 days , termed the early bactericidal activity ( EBA ) , was estimated from counts of colony-forming units ( cfu ) on selective 7H-11 agar medium . The EBA for rifabutin ranged from -0.039 ( an increase in counts ) to 0.049 log10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log10 cfu/ml/day for 600 mg rifampicin and was 0.43 log10 cfu/ml/day for 300 mg isoniazid . The difference between the EBAs for rifabutin and rifampicin just attained significance ( P = 0.05 ) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities . Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin . The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro ABSTRACT We studied the early bactericidal activity of twice the st and ard dose of rifampin in subjects with pulmonary tuberculosis evidence d by positive smears . The observed mean 2-day activity was almost double that reported at the st and ard dose . Further studies are warranted to establish whether higher rifampin doses might assist in shortening tuberculosis treatment ABSTRACT Bedaquiline is a new antituberculosis agent targeting ATP synthase . This r and omized , double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg , 200 mg , 300 mg , and 400 mg bedaquiline , preceded by loading doses of 200 mg , 400 mg , 500 mg , and 700 mg , respectively , on the first treatment day and 100 mg , 300 mg , 400 mg , and 500 mg on the second treatment day . All groups showed activity with a mean ( st and ard deviation ) daily fall in log10 CFU over 14 days of 0.040 ( 0.068 ) , 0.056 ( 0.051 ) , 0.077 ( 0.064 ) , and 0.104 ( 0.077 ) in the 100-mg , 200-mg , 300-mg , and 400-mg groups , respectively . The linear trend for dose was significant ( P = 0.001 ) , and activity in the 400-mg dose group was greater than that in the 100-mg group ( P = 0.014 ) . All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period . The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials . To examine the relationship between slow culture conversion and peak plasma rifampicin level ( Cmax-rfm ) in a case-control study , patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with st and ard pyrazinamide-containing regimens were enrolled prospect ively in government chest clinics from 16 December 2005 to 15 November 2006 . Patients with multidrug-resistant tuberculosis , human immunodeficiency virus infection , or poor treatment adherence were excluded . Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear . Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm . A cohort of 88 patients was identified . After excluding 16 patients , there were 36 controls and 36 cases . None had symptoms of malabsorption . Cmax-rfm was below 6 mg/l among 47 % of controls and 44 % of cases . Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation . Thus , there is probably no association between Cmax-rfm and slow culture conversion It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis . The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment . Such trials are usually both long and expensive . Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens . The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome . Data were obtained from twelve r and omised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia , consisting of 6974 participants and 49 different treatment regimens . The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong . In contrast , the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong . As well as differences in location , ethnicity and probable strain of Mycobacteria tuberculosis , Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens , and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment . An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate . More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial BACKGROUND Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy , but efficacy and safety data are limited in humans . We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment . METHODS In total , 531 adults with sputum smear-positive pulmonary tuberculosis were r and omized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose , administered 5 days per week for 8 weeks ( intensive phase ) , with isoniazid , pyrazinamide , and ethambutol . Co primary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase . RESULTS Negative cultures on solid media occurred in 145 of 174 participants ( 83.3 % ) in the rifampin group and 171 of 198 participants ( 86.4 % ) in the rifapentine group ( difference , 3.0 % ; 95 % confidence interval [ CI ] : -4.3 , 10.5 ) ; negative cultures in liquid media occurred in 110 of 169 ( 65.1 % ) in the rifampin group and 133 of 196 ( 67.9 % ) in the rifapentine group ( difference , 2.8 % ; 95 % CI : -6.9 , 12.4 ) . Among 529 participants who received study therapy , 40 of 254 participants ( 15.7 % ) in the rifampin group and 40 of 275 participants ( 14.5 % ) in the rifapentine group prematurely discontinued treatment ( P=.79 ) . CONCLUSIONS The rifapentine regimen was safe but not significantly more active than a st and ard rifampin regimen , by the surrogate endpoint of culture status at completion of intensive phase . Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted . CLINICAL TRIALS REGISTRATION NCT00694629 RATIONALE Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis ( TB ) chemotherapy , but data regarding its activity in humans are limited . OBJECTIVES Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB . METHODS Adults with sputum smear-positive pulmonary TB were r and omly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo , or isoniazid 300 mg plus moxifloxacin placebo , administered 5 days/week for 8 weeks , in addition to rifampin , pyrazinamide , and ethambutol . All doses were directly observed . Sputum was collected for culture every 2 weeks . The primary outcome was negative sputum culture at completion of 8 weeks of treatment . MEASUREMENTS AND MAIN RESULTS Of 433 participants enrolled , 328 were eligible for the primary efficacy analysis . Of these , 35 ( 11 % ) were HIV positive , 248 ( 76 % ) had cavitation on baseline chest radiograph , and 213 ( 65 % ) were enrolled at African sites .  Negative cultures at Week 8 were observed in 90/164 ( 54.9 % ) participants in the isoniazid arm , and 99/164 ( 60.4 % ) in the moxifloxacin arm ( P = 0.37 ) . In multivariate analysis , cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity . The proportion of participants who discontinued assigned treatment was 31/214 ( 14.5 % ) for the moxifloxacin group versus 22/205 ( 10.7 % ) for the isoniazid group ( RR , 1.35 ; 95 % CI , 0.81 , 2.25 ) . CONCLUSIONS Substitution of moxifloxacin for isoniazid result ed in a small but statistically nonsignificant increase in Week-8 culture negativity RATIONALE Moxifloxacin has promising pre clinical activity against Mycobacterium tuberculosis , but has not been evaluated in multidrug treatment of tuberculosis in humans . OBJECTIVE To compare the impact of moxifloxacin versus ethambutol , both in combination with isoniazid , rifampin , and pyrazinamide , on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens . METHODS Adults with smear-positive pulmonary tuberculosis were r and omized in a factorial design to receive moxifloxacin ( 400 mg ) versus ethambutol given 5 d/wk versus 3 d/wk ( after 2 wk of daily therapy ) . All doses were directly observed . MEASUREMENTS The primary endpoint was sputum culture status at 2 mo of treatment . RESULTS Of 336 patients enrolled , 277 ( 
    Output:
    
Bacteriological results were as often expressed in terms of positivity as negativity , with varying definitions of culture conversion .