{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:27:37Z","timestamp":1793910457068,"version":"4.8.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a preliminary open-label study, we randomly 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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, \u221214.4% [95% confidence interval, \u221232.1 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>Clinical trial registered with http:\/\/www.umin.ac.jp\/english\/ (UMIN000002819).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201308-266oc","type":"journal-article","created":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T10:04:54Z","timestamp":1392372294000},"page":"23-29","source":"Crossref","is-referenced-by-count":123,"title":["Efficacy of Clarithromycin and Ethambutol for\n                    <i>Mycobacterium avium<\/i>\n                    Complex Pulmonary Disease. A Preliminary Study"],"prefix":"10.1093","volume":"11","author":[{"given":"Seiichi","family":"Miwa","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and"},{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and"},{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Yokomura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Inui","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingo","family":"Chida","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and"},{"name":"Department of Respiratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2026012303554528000_bib1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","article-title":"An official ATS\/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases","volume":"175","author":"Griffith","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1378\/chest.107.4.1035","article-title":"Clarithromycin in the treatment of Mycobacterium avium lung infections in patients without AIDS","volume":"107","author":"Dautzenberg","year":"1995","journal-title":"Chest"},{"key":"2026012303554528000_bib3","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1164\/ajrccm.149.5.8173775","article-title":"Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease","volume":"149","author":"Wallace","year":"1994","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib4","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1093\/clinids\/23.5.983","article-title":"Azithromycin activity against Mycobacterium avium complex lung disease in patients who were not infected with human immunodeficiency virus","volume":"23","author":"Griffith","year":"1996","journal-title":"Clin Infect Dis"},{"key":"2026012303554528000_bib5","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1164\/ajrccm.153.6.8665032","article-title":"Clarithromycin regimens for pulmonary Mycobacterium avium complex. The first 50 patients","volume":"153","author":"Wallace","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib6","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1086\/320512","article-title":"Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease","volume":"32","author":"Griffith","year":"2001","journal-title":"Clin Infect Dis"},{"key":"2026012303554528000_bib7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1164\/ajrccm.160.3.9811086","article-title":"Effect of clarithromycin regimen for Mycobacterium avium complex pulmonary disease","volume":"160","author":"Tanaka","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib8","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/infdis\/171.3.747","article-title":"Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection","volume":"171","author":"Wallace","year":"1995","journal-title":"J Infect Dis"},{"key":"2026012303554528000_bib9","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1164\/rccm.201204-0682OC","article-title":"The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment","volume":"186","author":"van Ingen","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib10","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1164\/rccm.201206-1088OC","article-title":"Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease","volume":"186","author":"Koh","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1183\/09031936.00074207","article-title":"Mycobacterium avium complex disease: prognostic implication of high-resolution computed tomography findings","volume":"32","author":"Kuroishi","year":"2008","journal-title":"Eur Respir J"},{"key":"2026012303554528000_bib12","volume-title":"Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes: approved standards","author":"Clinical and Laboratory Standards Institute","year":"2003"},{"key":"2026012303554528000_bib13","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/bmc.691","article-title":"Liquid chromatographic-electrospray tandem mass spectrometric determination of clarithromycin in human plasma","volume":"20","author":"Li","year":"2006","journal-title":"Biomed Chromatogr"},{"key":"2026012303554528000_bib14","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.jpba.2006.11.025","article-title":"Determination of clarithromycin in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry","volume":"43","author":"Jiang","year":"2007","journal-title":"J Pharm Biomed Anal"},{"key":"2026012303554528000_bib15","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1164\/rccm.200603-450OC","article-title":"Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease","volume":"174","author":"Griffith","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012303554528000_bib16","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1086\/514748","article-title":"A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex","volume":"28","author":"Gordin","year":"1999","journal-title":"Clin Infect Dis"},{"key":"2026012303554528000_bib17","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1378\/chest.08-2567","article-title":"Therapeutic effects of various initial combinations of chemotherapy including clarithromycin against Mycobacterium avium complex pulmonary disease","volume":"136","author":"Hasegawa","year":"2009","journal-title":"Chest"},{"key":"2026012303554528000_bib18","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s10156-011-0351-x","article-title":"Relationship between clinical efficacy for pulmonary MAC and drug-sensitivity test for isolated MAC in a recent 6-year period","volume":"18","author":"Kobashi","year":"2012","journal-title":"J Infect Chemother"},{"key":"2026012303554528000_bib19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0732-8893(93)90112-K","article-title":"Drug intolerance to high-dose clarithromycin among elderly patients","volume":"16","author":"Wallace","year":"1993","journal-title":"Diagn Microbiol Infect Dis"}],"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/11\/1\/23\/66485605\/annalsats_11_1_23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/11\/1\/23\/66485605\/annalsats_11_1_23.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:56:04Z","timestamp":1769158564000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/11\/1\/23\/8432066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,1]]},"published-print":{"date-parts":[[2014,1,1]]}},"URL":"https:\/\/doi.org\/10.1513\/annalsats.201308-266oc","relation":{},"ISSN":["2329-6933","2325-6621"],"issn-type":[{"value":"2329-6933","type":"print"},{"value":"2325-6621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,1]]},"published":{"date-parts":[[2014,1,1]]}}}