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 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. 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).
RCT Entities:
RATIONALE: Patients with Mycobacterium avium complexpulmonary 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 complexpulmonary 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 aviumlung disease. METHODS: 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. 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 complexlung 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).
Authors: Charles L Daley; Jonathan M Iaccarino; Christoph Lange; Emmanuelle Cambau; Richard J Wallace; Claire Andrejak; Erik C Böttger; Jan Brozek; David E Griffith; Lorenzo Guglielmetti; Gwen A Huitt; Shandra L Knight; Philip Leitman; Theodore K Marras; Kenneth N Olivier; Miguel Santin; Jason E Stout; Enrico Tortoli; Jakko van Ingen; Dirk Wagner; Kevin L Winthrop Journal: Eur Respir J Date: 2020-07-07 Impact factor: 16.671
Authors: Charles L Daley; Jonathan M Iaccarino; Christoph Lange; Emmanuelle Cambau; Richard J Wallace; Claire Andrejak; Erik C Böttger; Jan Brozek; David E Griffith; Lorenzo Guglielmetti; Gwen A Huitt; Shandra L Knight; Philip Leitman; Theodore K Marras; Kenneth N Olivier; Miguel Santin; Jason E Stout; Enrico Tortoli; Jakko van Ingen; Dirk Wagner; Kevin L Winthrop Journal: Clin Infect Dis Date: 2020-08-14 Impact factor: 9.079
Authors: Vidhisha V Sonawane; Mike M Ruth; Lian J Pennings; Elin M Svensson; Heiman F L Wertheim; Wouter Hoefsloot; Jakko van Ingen Journal: Antimicrob Agents Chemother Date: 2021-07-16 Impact factor: 5.191
Authors: Charles L Daley; Jonathan M Iaccarino; Christoph Lange; Emmanuelle Cambau; Richard J Wallace; Claire Andrejak; Erik C Böttger; Jan Brozek; David E Griffith; Lorenzo Guglielmetti; Gwen A Huitt; Shandra L Knight; Philip Leitman; Theodore K Marras; Kenneth N Olivier; Miguel Santin; Jason E Stout; Enrico Tortoli; Jakko van Ingen; Dirk Wagner; Kevin L Winthrop Journal: Clin Infect Dis Date: 2020-08-14 Impact factor: 9.079