***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: In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to four 6-month regimens of chemotherapy , all given three times weekly from the start and all containing isoniazid ( H ) and rifampin ( R ) throughout . Three contained streptomycin ( S ) for the first 4 months and pyrazinamide ( Z ) for 2 months ( Z2 ) , 4 months ( Z4 ) , or 6 months ( Z6 ) ; the fourth contained pyrazinamide for 6 months but no streptomycin ( Z6noS ) . Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis . During the later part of the intake patients were allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 125 mg isoniazid , 100 mg rifampin , and 375 mg pyrazinamide , or as the three drugs separately . Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment , bacteriologic failure during chemotherapy occurred in 4 , all Z6noS ( 2 % of 224 ; p less than 0.005 for the comparison with the S-containing regimens ) . During 30 months of follow-up after the end of chemotherapy , bacteriologic relapse occurred in 2 ( 3 % ) of 71 Z2 , 2 ( 3 % ) of 72 Z4 , 4 ( 6 % ) of 66 Z6 , and 6 ( 9 % ) of 64 Z6noS patients allocated to Rifater , and in 4 ( 3 % ) of 149 Z2 , 8 ( 6 % ) of 133 Z4 , 2 ( 1 % ) of 142 Z6 , and 6 ( 4 % ) of 135 Z6noS patients allocated to separate drugs . In the relapse rates there were no significant differences between the Rifater and separate drug regimens , the different duration s of pyrazinamide , or the regimens with and without streptomycin . ( ABSTRACT TRUNCATED AT 250 WORDS The time is now right for r and omized trials of MDR-TB , say the authors , as the expansion of MDR-TB programs provides the setting in which trials can be implemented . In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to daily chemotherapy with streptomycin , isoniazid , rifampin , and pyrazinamide ( 1 ) for 2 months ( 2SHRZ ) , ( 2 ) for 1 month ( 1SHRZ ) , or ( 3 ) for 2 months without streptomycin ( 2HRZ ) . This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months . During the initial period of daily chemotherapy the patients were also allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 50 mg isoniazid , 120 mg rifampin , and 300 mg pyrazinamide , or as three separate drugs . During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting , reported by 8 % of 155 patients receiving Rifater and 7 % of 155 separate drugs . Other adverse effects were also reported in similar proportions in the two series . Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy . During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 ( 7 % ) of 46 2SHRZ , 2 ( 5 % ) of 42 1SHRZ , and 3 ( 8 % ) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ , 1 ( 2 % ) of 46 1SHRZ , and 1 ( 2 % ) of 44 2HRZ patients allocated to separate drugs . There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ . The relapse rates were slightly higher in the Rifater series ( p = 0.04 ) . Further follow-up and results from other studies are therefore needed fully to assess the combined preparation Five 6-month antituberculosis regimens , allocated at r and om to patients with acid-fast bacilli in their sputum on microscopy , were studied . Four , given three times a week from the start , contained isoniazid and rifampicin together with ( 1 ) streptomycin , pyrazinamide , and ethambutol , ( 2 ) streptomycin and pyrazinamide , ( 3 ) streptomycin and ethambutol , or ( 4 ) pyrazinamide and ethambutol . The fifth was daily isoniazid , rifampicin , pyrazinamide , and ethambutol .  All 833 patients with drug-sensitive strains of bacilli before treatment had a  favourable bacteriological response during chemotherapy , and the bacteriological relapse rates during 12 months after stopping chemotherapy were 2 % or less for all regimens except thrice-weekly isoniazid , rifampicin , streptomycin , and ethambutol ( the only regimen without pyrazinamide ) , which had a relapse rate of 8 % . The results were equally good for the 138 patients with bacilli resistant to isoniazid , streptomycin , or both drugs initially . The incidence of potentially serious toxicity was low . The daily regimen is relevant to programmes in which patients self-administer their drugs , and the 3 pyrazinamide-containing intermittent regimens are relevant to fully supervised outpatient programmes A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed , sputum-positive pulmonary tuberculosis . The patients were allocated at r and om to one of three regimens : a ) Rifampicin , streptomycin , isoniazid and pyrazinamide daily for 3 months ( R3 ) ; b ) the same regimen as above but followed by streptomycin , isoniazid and pyrazinamide twice-weekly for a further period of 2 months ( R5 ) ; c ) the same as R5 but without rifampicin ( Z5 ) . A bacteriological relapse requiring treatment occurred by 5 years in 16.8 % of 113 R3 , 5.2 % of 97 R5 , and 20.0 % of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially . The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant ( p less than 0.01 for both ) . Considering patients with organisms initially resistant to streptomycin or isoniazid or both , 7 of 52 patients ( 4 R3 , 2 R5 , 1 Z5 ) had a bacteriological relapse requiring retreatment Four short-course antituberculosis regimens allocated at r and om were studied ; ( 1 ) streptomycin , isoniazid , and rifampin given daily for 6 months ; ( 2 ) these 3 drugs plus pyrazinamide given daily for 2 months , followed by twice-weekly administration of streptomycin , isoniazid , and pyrazinamide ; ( 3 ) a regimen that differed from regimen 2 only in that ethambutol replaced pyrazinamide , and ( 4 ) streptomycin plus isoniazid plus rifampin plus pyrazinamide given 3 times per week for 4 months , followed by streptomycin plus isoniazid plus pyrazinamide administered twice per week . The last 3 regimens were given for 6 or 8 months at r and om . All except 1 of 680 patients with tubercle bacilli drug-susceptible before treatment had a favorable bacteriologic response during chemotherapy . The relapse rates during the first 6 months after chemotherapy were low , except in the ethambutol series , in which 19 per cent of the patients relapsed after 6 months of treatment , and 8 per cent relapsed after 8 months . A substantial proportion of the patients with strains initially resistant to either isoniazid or streptomycin had a favorable response to their allocated regimen , but the results were not as good for those patients with strains resistant to both drugs . An important finding is that the incidences of immunologic febrile reactions to rifampin and of rifampin-dependent antibodies were very low during the 3-times-weekly regimen One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared . The daily regimen was rifampicin and ethambutol ( RE7 ) . The three intermittent regimens also contained rifampicin and ethambutol : one of them , rifampicin and ethambutol throughout ( RE3 ) ; the next one supplemented with pyrazinamide for the first 3 months ( REZ3 ) ; the last one supplemented with prothionamide for the first 3 months ( REPt3 ) . The pyrazinamide containing regimen was subdivided into ordinary and high dose groups . The subjects for retreatment were those who have had , at least , more than 6 months of initial triple chemotherapy of isoniazid , PAS and streptomycin at the health centres , and failed to convert to bacteriologically negative status . Among 419 patients who were available for sensitivity tests before commencing retreatment , 393 ( 94.3 % ) were resistant to isoniazid . Six hundred and seventy-four patients ( 674 ) were allocated r and omly to the regimens : 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy . There remain 501 patients who completed their retreatment . As assessed at 12 months , a bacteriologically favourable response was achieved in 68 % of 135 RE7 patients , 62 % of 129 RE3 patients , 74 % of 132 REZ3 patients , and in 79 % of 108 REPt3 patients . Adverse reactions were uncommon : 4 % in RE7 , 5 % in RE3 and 9 % in REZ3 , but 32 % in REPt3 . Relapse rates during 2 years after termination of chemotherapy were 15 % in RE7 , 14 % in RE3 and REZ3 , and 26 % in REPt3 , as calculated by life table analysis This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol ( RHZ and RHE regimens ) against a st and ard daily regimen of streptomycin , isoniazid , and ethambutol ( SHE regimen ) given for 6 months followed by isoniazid and ethambutol for an additional 6 months . Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study . Three hundred and fifty-eight patients were admitted to the study and 267 ( 75 % ) completed chemotherapy .  Eighty-five percent of RHZ-regimen and 82 % of RHE-regimen patients achieved sputum culture negativity compared to 55 % of patients in SHE regimen . Successfully treated patients were followed up for 18 months , and among these , all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period . Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period , and no statistically significant difference in relapse rate was noticed in the 3 regimens . Severe drug intolerance necessitated discontinuation of therapy in only 2 patients A total of 481 adult Chinese , Malays , and Indians in Singapore with newly diagnosed smear-positive pulmonary tuberculosis were allocated at r and om to four regimens of intermittent rifampicin plus isoniazid . All patients received an initial 2 weeks of daily streptomycin plus isoniazid plus rifampicin . This was followed either by twice-weekly isoniazid 15 mg/kg plus rifampicin 900 mg ( HR2 regimen ) or 600 mg ( LR2 regimen ) , or by once-weekly isoniazid 15 mg/kg plus rifampicin 900 mg ( HR1 regimen ) or 600 mg ( LR1 regimen ) . In addition , all patients received a daily capsule containing , at r and om , either rifampicin 25 mg or a matched placebo to see if the rifampicin supplement would reduce the incidence of adverse reactions to the drug . At 12 months , all the patients on the two twice-weekly regimens ( HR2 , LR2 ) had a favourable bacteriological status as had 97 % of 102 HR1 and 93 % of 112 LR1 patients . The therapeutic response was significantly better on the twice-weekly than on the once-weekly regimens ( P = 0 - 0005 ) , but the dose size of rifampicin did not have a statistically significant effect . Adverse reactions to intermittent rifampicin occurred in 25 % of the HR1 patients but on the other three regimens their incidence was low . The incidence of rifampicin-dependent antibodies was higher , ranging from  
    Output:
    
From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid , lower failure , relapse , and acquired drug resistance rates were associated with longer duration of rifampin , use of streptomycin , daily therapy initially , and treatment with a greater number of effective drugs .