Department of Clinical Laboratory, Juntendo University, Faculty of Medicine & Graduate School of Medicine, Tokyo, Japan.
Department of Respiratory Medicine, Juntendo University, Faculty of Medicine & Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
BMC Microbiol. 2020 Oct 19;20(1):316. doi: 10.1186/s12866-020-02000-5.
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.
非结核分枝杆菌(NTM)是普遍存在的生物体,近年来 NTM 感染的发病率一直在上升。类鼻疽伯克霍尔德菌(M. abscessus)是最具抗药性的 NTM 之一;然而,目前还没有可靠的抗生素方案可以被正式推荐。我们评估了克拉霉素联合各种抗菌药物治疗 M. abscessus 复合体的疗效。
从各种临床标本中分离出 29 株临床 M. abscessus 菌株。其中,10 株(34.5%)为 M. abscessus 亚种脓肿亚种,18 株(62.1%)为 M. abscessus 亚种马萨里亚种,1 株(3.4%)为 M. abscessus 亚种 bolletii。测量了三种抗菌药物(阿米卡星、亚胺培南和莫西沙星)在有无克拉霉素的情况下的 MIC。与克拉霉素和亚胺培南单药治疗相比,亚胺培南-克拉霉素联合显著降低了 MIC,包括对耐药株。M. abscessus 复合体的敏感性与每种联合用药之间的关联具有统计学意义(p=0.001)。调整后的残差表明,亚胺培南-克拉霉素联合具有协同作用(调整后的残差=3.1),并抑制了拮抗作用(调整后的残差=-3.1)。在 M. abscessus 复合体的亚种中,与 M. abscessus 亚种马萨里亚种敏感性的关联也具有统计学意义(p=0.036:协同和拮抗作用的调整后的残差分别为 2.6 和-2.6)。与 M. abscessus 亚种脓肿亚种敏感性的关联也显示出类似的趋势,但没有达到统计学意义。
我们的数据表明,由于能够恢复抗菌药物敏感性,亚胺培南-克拉霉素联合治疗可能是治疗 M. abscessus 复合体的推荐治疗选择。