Abstract：
Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
摘要：
难以治疗的分枝杆菌感染正在全球增加。对于耐多药结核分枝杆菌（MTB），迫切需要新的治疗替代方案。以及非结核分枝杆菌，例如脓肿分枝杆菌复合物（MABC）和鸟分枝杆菌复合物（MAC）。最近,新的碳青霉烯类抗生素和碳青霉烯类抗生素与β-内酰胺酶抑制剂的组合已经可用，但是到目前为止，体外对分枝杆菌的活性数据还很少。因此,我们对碳青霉烯类抗生素的最低抑制浓度（MIC）进行了系统评价，有或没有β-内酰胺酶抑制剂的MTB，MABC,和MAC。截至2022年9月21日，在PubMed和WebofScience数据库中搜索了相关的英文文章。研究的筛选由两名独立的评审员进行。包括通过推荐方法获得的至少五个单独MIC的MIC数据。数据报告为MIC范围，MIC50，模态MIC，和/或直方图，当个别MIC可用时。研究方案在PROSPERO(CRD42021258537)注册。筛选后,本综述共纳入75项研究,其中碳青霉烯类抗生素使用或不使用β-内酰胺酶抑制剂的MIC数据.对于MTB，口服碳青霉烯替比培南与β-内酰胺酶抑制剂克拉维酸合用导致MIC的显著降低。对于MABC，在替比培南中加入阿维巴坦可使模态MIC降低64倍.数据不足以分析MAC。碳青霉烯类,特别是新型口服化合物替比培南，与克拉维酸联合用于MTB和阿维巴坦联合用于MABC可能是难以治疗的分枝杆菌感染的未开发潜力.
