***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: SETTING AND OBJECTIVE Previous reports on small numbers highlighted the need for a prospect i ve study of the clinical features and response to treatment of pulmonary disease caused by Mycobacterium avium-intracellulare ( MAC ) . DESIGN AND METHODS Patients with two positive cultures were r and omised to 2 years of rifampicin and ethambutol or of rifampicin , ethambutol and isoniazid .  Clinical , bacteriological and radiological progress was monitored for 5 years . RESULTS Seventy-five patients entered the study . They had a mean age of 64 years ( range 29 - 87 ) and the sexes were balanced . Approximately two-thirds had previous/ co-existing lung disease(s ) . Sputum was positive on direct smear in 56 % , and cavitation was observed in 61 % , most having at least one large cavity . Just under half had bilateral disease and one-third extensive disease . Disease was confined to upper zone(s ) in 25 % . Twenty-seven ( 36 % ) died within 5 years , three because of MAC disease . There were 11 treatment failures and 10 relapses , with no correlation between those and in vitro resistance . Forty-five ( 60 % ) were alive at 5 years , of whom 23 were confirmed cured . CONCLUSION Pulmonary disease caused by MAC is associated with high morbidity and mortality . St and ard susceptibility tests do not correlate with the response of the disease to chemotherapy . Rifampicin and ethambutol , with or without isoniazid , cured 31 % , a result comparable with or better than that found previously with more toxic regimens , but mortality ( 36 % ) remains high . More effective regimens are needed , and management of coexisting illnesses and general health needs to be to maximised RATIONALE Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin , ethambutol , and rifampicin . However , rifampicin is known to reduce the serum levels of clarithromycin . It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen . OBJECTIVES To compare a three-drug regimen ( clarithromycin , ethambutol , and rifampicin ) to a two-drug regimen ( clarithromycin and ethambutol ) for the treatment of Mycobacterium avium lung disease . METHODS In a preliminary open-label study , we r and omly assigned newly diagnosed , but as-yet untreated , patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months . The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment . Patient data were analyzed using the intention-to-treat method . MEASUREMENTS AND MAIN RESULTS Of 119 eligible patients , 59 were assigned to the three-drug regimen and 60 to the two-drug regimen . The rate of sputum culture conversion was 40.6 % with the three-drug regimen and 55.0 % with the two-drug regimen ( difference , -14.4 % [ 95 % confidence interval , -32.1 to 3.4 ] ) . The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6 % for the three-drug and the two-drug regimens , respectively . CONCLUSIONS This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin , ethambutol , and rifampicin for Mycobacterium avium complex lung disease . Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens . Clinical trial registered with http://www.umin.ac.jp/english/ ( UMIN000002819 ) SETTING An open clinical trial for the treatment of Mycobacterium avium intracellulare complex ( MAIC ) lung disease in human immunodeficiency virus (HIV)-seronegative patients . OBJECTIVE To assess the efficacy and tolerance of clarithromycin ( 0.75 - 2 g/day ) combined with minocycline ( 200 mg/day ) and clofazimine ( 100 mg/day ) for 15 months . DESIGN The study was carried out from August 1992 to June 1994 by pulmonologists of various French medical centres . The patients to be enrolled were of either sex , over 18 years of age , HIV-seronegative and suffering from MAIC lung disease , with a confirmed bacteriological and radiological diagnosis . Examinations were to be performed after 1 , 2 , 3 , 6 , 9 , 12 and 15 months of treatment . RESULTS Thirty patients were included , 16 males and 14 females . Eight did not complete the study due to deviations from protocol or adverse effects . The remainder completed the study with a post-treatment follow-up of 27 + /- 7 months . Among the 22 evaluable patients , 18 had a history of lung disease .  Tolerance to the drugs was generally good , apart from three cases of hepatic disturbances and three cases of ototoxicity , which required a decrease in clarithromycin dosage after a short interruption of treatment . There were 14 treatment successes , seven treatment failures , defined by absence of bacteriologic conversion , and in one patient the disease evolution remains uncertain . CONCLUSION The combination of clarithromycin with minocycline and clofazimine proved effective with persistently negative cultures in 64 % of the patients , and an overall good drug tolerance Background : The difficulty of treatment for pulmonary Mycobacterium avium complex ( MAC ) in Japan . Objectives : To investigate the clinical and microbiological effects of treatment according to the guidelines proposed by the American Thoracic Society and the Japanese Society for Tuberculosis and prospect i ve follow-up studies after the completion of treatment of patients with pulmonary MAC disease . Methods : Analysis of the microbiological effects with regard to sputum conversion rate and the sputum relapsing rate and the clinical effects with regard to clinical symptoms and radiological findings for patients with pulmonary MAC disease treated with a regimen consisting of rifampicin , ethambutol , streptomycin , and clarithromycin over 24 months and follow-up over 12 months . Results : Sixty-five patients with pulmonary MAC disease were enrolled in this trial . In 39 patients , negative sputum conversion was observed within 6 months after the initiation of this regimen , 16 relapsed , and 20 experienced clinical worsening within 1 year after the completion of treatment . Although retreatment with the same regimen or a regimen including new quinolones was carried out for these patients , we could not achieve negative sputum conversion and /or clinical improvement . Conclusions : We believe that the dose of clarithromycin for pulmonary MAC disease may be increased and recommend surgery for patients with a localized lesion at early-stage MAC disease to prevent a high rate of relapse We initiated a prospect i ve trial of an azithromycin-containing regimen for the treatment of human immunodeficiency virus-negative patients with Mycobacterium avium complex ( MAC ) lung disease ; the initial 4 months of therapy were with azithromycin ( 600 mg/d ) alone . The primary study endpoint was microbiological response measured at 4 and 6 months of therapy . Of 29 patients enrolled in the study , 23 completed therapy . Fifty-two percent of these 23 patients were male , and 65 % were smokers . All 23 patients were older than 45 years of age ; 83 % had bilateral disease , and 48 % had fibrocavitary disease .  Macrolide (clarithromycin)-susceptible  MAC isolates were recovered from these 23 patients before treatment . Cultures of sputum from 38 % of these patients became negative , and the positivity of cultures of sputum from 76 % of these patients was significantly reduced . Sixty-eight percent of sputum cultures were strongly positive ( > 200 colonies ) before therapy , while only 27 % were strongly positive after therapy . Although most patients continued to receive 600 mg of azithromycin/d , the high incidence of gastrointestinal side effects ( 76 % ) and altered hearing ( 41 % ) suggests the need for lower or less frequent dosing .  Macrolide ( clarithromycin ) resistance did not develop in any MAC isolates during monotherapy . These results , which demonstrate that azithromycin is active against MAC pulmonary disease , provide a rationale to include this drug in the initial multidrug regimens recommended for the treatment of this disease We initiated a prospect i ve noncomparative trial of treatment for lung disease due to Mycobacterium avium complex ( MAC ) in human immunodeficiency virus-negative patients , with a regimen of clarithromycin ( 1000 mg ) , rifabutin ( 300 - 600 mg ) , and ethambutol ( 25 mg/kg ) administered 3 times per week . Fifty-nine patients were enrolled . Twelve ( 20 % ) were lost to follow-up , and 6 ( 10 % ) developed clarithromycin intolerance . The remaining 41 patients ( 69 % ) completed the initial 6 months of therapy . The sputum of 32 of these patients ( 78 % ) converted to negative . When results were compared with the sputum response rates at 6 months in previous studies with a regimen including daily clarithromycin and regimens including intermittent ( 3 times per week ) azithromycin with the same companion drugs , no differences in treatment responses were evident . Adverse reactions related to rifabutin were a major problem , and for 24 ( 41 % ) of 59 patients the dosage was decreased or the drug was withdrawn . Intermittent ( 3 times per week ) administration of clarithromycin appears to be as effective as daily administration in effecting sputum conversion in pulmonary MAC disease OBJECTIVE To investigate whether the combined therapy according to the guideline proposed by American Thoracic Society ( ATS ) and Japanese Society for Tuberculosis ( JST ) is clinical ly appropriate for Mycobacterium avium complex ( MAC ) pulmonary disease . PATIENTS Seventy-one patients in whom MAC pulmonary disease was diagnosed at Kawasaki Medical School and our associated ten hospitals were prospect ively studied . RESULTS Seventy-one patients with Mycobacterium avium complex ( MAC ) pulmonary disease were 27 males and 44 females with a mean age of 64.4 + /- 10.2 years old . Patients received 400 mg/day or 600 mg/day of clarithromycin plus ethambutol , rifampicin , and initial streptomycin for 12 months . Among 71 patients who received more than 12 months of therapy , 41 patients ( 57.7 % ) converted their sputum to negative within six months after the initiation of this regimen , 16 of 41 patients ( 39.0 % ) relapsed , and 23 of 71 patients ( 32.4 % ) obtained clinical improvement on chest X-ray and /or clinical symptoms . The mortality rate had a comparatively good prognosis with a low incidence of 2.8 % . Although the species of pathogen ( M. avium or M. intracellulare ) did not significantly affect the conversion rate or clinical improvement , the infectious form with or without respiratory underlying disease , the characteristics and extent of lesion on chest X-ray , and the dose of clarithromycin significantly influenced the conversion rate or clinical improvement . There were no problems concerning adverse reactions for this regimen . CONCLUSION This combined therapy , according to the guideline proposed by ATS and JST , was one of the effective treatments compared to the clinical effect of only antituberculous drugs through this study . However , this combined therapy was unsatisfactory compared to the clinical effect for pulmonary tuberculosis . The development of new companion drugs for MAC pulmonary diseases is needed Intermediate results of the first 50 patients treated with clarithromycin ( CLARI ) regimens for Mycobacterium avium-intracellulare ( MAI ) lung disease were evaluated . Patients were HIV negative , and pretreatment isolates were susceptible to CLARI . Patients received CLARI 500 mg twice daily , ethambutol , rifampin ( RMP ) , or rifabutin ( RBT ) and initial streptomycin , and they were treated until culture-negative 1 yr . Eleven of 50 patients ( 22 % ) were dropped in the first 3 mo . Of the remaining 39 patients , 36 ( 92 % ) converted their sputa to negative , and 32 ( 82 % ) remain culture negative to date . This includes 11 of 16 ( 69 % ) with prior drug therapy and 21 of 23 ( 91 % ) with no prior therapy . One or more companion drugs were discontinued in 16 of 39 ( 41 % ) of patients because of adverse events . Isolates from six of 39 patients ( 15 % ) became CLARI-resistant  . Of 23 patients who are alive and were culture-negative  a mean of 12.0 mo while receiving therapy , all remain culture-negative without therapy a mean of 19.1 mo . Despite reduced  CLARI serum levels in patients also receiving RMP , 10 of 13 patients ( 77 % ) receiving this regimen were successfully treated . Although not directly compared with previous regimens , the success of this regimen strongly suggests it is superior to previous non-CLARI-containing regimens OB 
    Output:
    
Nevertheless , these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens