The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex

亚胺培南-克拉霉素联合治疗脓肿分枝杆菌复合体的协同作用

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作者:Satomi Takei, Hiroaki Ihara, Shinsaku Togo, Ayako Nakamura, Yuichi Fujimoto, Junko Watanabe, Kana Kurokawa, Kohei Shibayama, Issei Sumiyoshi, Yusuke Ochi, Moe Iwai, Takahiro Okabe, Masayoshi Chonan, Shigeki Misawa, Akimichi Ohsaka, Kazuhisa Takahashi

Background

Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex.

Conclusion

Our data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility.

Results

Twenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = - 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and - 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance.

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