Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?
Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?
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DOI：
10.1093/jac/dkz511
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发表时间：
2020-03-01
影响因子：
5.2
通讯作者：
van Ingen, Jakko
中科院分区：
文献类型：
--
作者：
Ruth, Mike Marvin;Koeken, Valerie A. C. M.;van Ingen, Jakko
背景资料：非结核分枝杆菌（NTM）引起的肺部感染是很难治疗的，尽管有密集的多药therapeutic.Objectives：为了评估替地唑胺，一种新的恶唑烷酮，用于治疗鸟分枝杆菌和Mycobacteriumsessus.Methods：我们确定了替地唑胺的MIC为113株NTM。使用棋盘法和计算FIC指数（FICI）评估与关键抗分枝杆菌药物的协同作用。我们进行了替地唑胺单独和与阿米卡星联合治疗M。用乙胺丁醇处理M. avium用M. P.结果：NTM分离株的替地唑胺MIC通常低于利奈唑胺。替地唑胺和阿米卡星对M.替地唑胺与乙胺丁醇对M.鸟类（FICI = 0.72）。克拉霉素和替地唑胺显示出初始协同作用，但这种协同作用被红霉素（41）诱导的大环内酯类耐药（FICI = 0.53）所消除。替地唑胺对M.与丁胺卡那霉素合用后，其作用稍有延长。替地唑胺对M.乙胺丁醇可增强其药效。两种组合具有浓度依赖性协同效应。替地唑胺对两种M. avium和M.结论：替地唑胺对M.鸟类复杂性肺病它对M的活性较低。但还是很有希望。
Background: Pulmonary infections caused by non-tuberculous mycobacteria (NTM) are hard to treat and have low cure rates despite intensive multidrug therapy.Objectives: To assess the feasibility of tedizolid, a new oxazolidinone, for the treatment of Mycobacterium avium and Mycobacterium abscessus.Methods: We determined MICs of tedizolid for 113 isolates of NTM. Synergy with key antimycobacterial drugs was assessed using the chequerboard method and calculation of the FIC index (FICI). We performed time-kill kinetics assays of tedizolid alone and combined with amikacin for M. abscessus and with ethambutol for M. avium. Human macrophages were infected with M. abscessus and M. avium and subsequently treated with tedizolid; intracellular and extracellular cfu were quantified over time.Results: NTM isolates generally had a lower MIC of tedizolid than of linezolid. FICIs were lowest between tedizolid and amikacin for M. abscessus (FICI = 0.75) and between tedizolid and ethambutol for M. avium (FICI = 0.72). Clarithromycin and tedizolid showed initial synergy, which was abrogated by erm(41)-induced macrolide resistance (FICI = 0.53). Tedizolid had a weak bacteriostatic effect on M. abscessus and combination with amikacin slightly prolonged its effect. Tedizolid had concentration-dependent activity against M. avium and its efficacy was enhanced by ethambutol. Both combinations had a concentration-dependent synergistic effect. Tedizolid could inhibit the intracellular bacterial population of both M. avium and M. abscessus.Conclusions: Tedizolid should be further investigated in pharmacodynamic studies and clinical trials for M. avium complex pulmonary disease. It is less active against M. abscessus, but still promising.