Kozo Morimoto1, Taku Nakagawa2, Takahiro Asami3, Eriko Morino4, Hiroshi Fujiwara3, Isano Hase5, Yoshie Tsujimoto4, Kiyohiko Izumi6, Yuta Hayashi2, Shuichi Matsuda7, Yoshiro Murase8, Ryozo Yano7, Jin Takasaki4, Tomoko Betsuyaku3, Akio Aono8, Hajime Goto7, Tomoyasu Nishimura9, Yuka Sasaki7, Yoshihiko Hoshino10, Atsuyuki Kurashima7, Manabu Ato10, Kenji Ogawa2, Naoki Hasegawa11, Satoshi Mitarai12. 1. Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan; Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. Electronic address: morimotok@fukujuji.org. 2. Department of Respiratory medicine, National Hospital Organization, Higashinagoya National Hospital, Nagoya, Japan. 3. Division of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan. 4. Department of Respiratory Medicine, Division of Infectious Diseases, National Center for Global Health and Medicine, Tokyo, Japan. 5. Department of Respiratory Medicine, National Hospital Organization, Utsunomiya Hospital, Utsunomiya, Japan. 6. Department of Epidemiology and Clinical Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan; Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. 7. Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan. 8. Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. 9. Keio University Health Center, Keio University, Tokyo, Japan. 10. Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan. 11. Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan. 12. Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan; Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Abstract
RATIONALE: No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. OBJECTIVES: This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. METHODS: A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. RESULTS: Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessus patients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 μg/ml v.s 2.0 μg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. CONCLUSIONS: Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.
RATIONALE: No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. OBJECTIVES: This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. METHODS: A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. RESULTS: Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessuspatients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 μg/ml v.s 2.0 μg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. CONCLUSIONS: Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.