Masahiro Shirata1, Yuta Yoshimoto2, Satoshi Marumo3, Kiyoko Tamai4, Motonari Fukui5. 1. Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Electronic address: mshirata@kuhp.kyoto-u.ac.jp. 2. Miroku Medical Laboratory Inc. 659-2 Innai, Saku-shi, Nagano 384-2201, Japan. Electronic address: mml-idenshi@miroku-lab.co.jp. 3. Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Electronic address: s-marumo@kitano-hp.or.jp. 4. Miroku Medical Laboratory Inc. 659-2 Innai, Saku-shi, Nagano 384-2201, Japan. Electronic address: tamai@miroku-lab.co.jp. 5. Respiratory Disease Center, Tazuke Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Electronic address: mfukui@kitano-hp.or.jp.
Abstract
OBJECTIVES: A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections. METHODS: We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method. RESULTS: We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively. CONCLUSIONS: These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.
OBJECTIVES: A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections. METHODS: We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method. RESULTS: We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively. CONCLUSIONS: These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massilienseinfections.