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The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex
BMC Microbiology ( IF 4.2 ) Pub Date : 2020-10-19 , DOI: 10.1186/s12866-020-02000-5
Satomi Takei 1 , Hiroaki Ihara 2, 3 , Shinsaku Togo 2, 4 , Ayako Nakamura 5 , Yuichi Fujimoto 2 , Junko Watanabe 2 , Kana Kurokawa 2 , Kohei Shibayama 2 , Issei Sumiyoshi 2 , Yusuke Ochi 2 , Moe Iwai 2, 4 , Takahiro Okabe 6 , Masayoshi Chonan 1 , Shigeki Misawa 1 , Akimichi Ohsaka 7 , Kazuhisa Takahashi 2
Affiliation  

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. 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. 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.

中文翻译:

亚胺培南-克拉霉素联合治疗分枝杆菌脓肿复合体的协同作用

非结核分枝杆菌 (NTM) 是无处不在的生物,近年来 NTM 感染的发生率一直在增加。脓肿分枝杆菌 (M. abscessus) 是最具有抗药性的 NTM 之一;然而,没有任何可靠的抗生素方案可以被正式提倡。我们评估了克拉霉素联合各种抗菌药物对脓肿分枝杆菌复合物的疗效。从各种临床样品中分离出 29 种脓肿分枝杆菌临床菌株。在分离株中,10 个 (34.5%) 是脓肿分枝杆菌亚种。脓肿,18 (62.1%) 的 M. abscessus subsp。massiliense 和 1 (3.4%) M. abscessus subsp。牛肝菌。在有或没有克拉霉素的情况下测量了三种抗菌剂(阿米卡星、亚胺培南和莫西沙星)的 MIC。与克拉霉素和亚胺培南单一疗法相比,亚胺培南-克拉霉素组合显着降低了 MIC,包括针对耐药菌株。脓肿分枝杆菌复合体的易感性与每种药物组合之间的关联是显着的(p = 0.001)。调整后的残留物表明亚胺培南-克拉霉素组合具有协同作用(调整后的残留物 = 3.1)并抑制拮抗作用(调整后的残留物 = - 3.1)。在 M. abscessus complex 亚种中,与 M. abscessus subsp. 的易感性相关。massiliense 同样具有统计学意义(p = 0.036:协同和拮抗作用的调整残差分别为:2.6 和 - 2.6)。与 M. abscessus subsp 易感性的关联。脓肿也表现出类似的趋势,但没有达到统计学意义。我们的数据表明,亚胺培南-克拉霉素组合可能是治疗脓肿分枝杆菌复合体的推荐治疗选择,因为它能够恢复抗菌药物敏感性。
更新日期:2020-10-19
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