ABSTRACT

Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed.

Areas covered: We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP.

Expert opinion: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have relevant literature. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future.

摘要

简介：呼吸机相关性肺炎 (VAP) 是机械通气的常见且可能致命的并发症，通常由耐多药 (MDR) 革兰氏阴性菌 (GNB) 引起。尽管重新利用旧的治疗方法和新的抗菌药物，但无法解决许多耐药机制，需要新的疗法。

涵盖的领域：我们在文献中搜索了有关机械通气患者 GNB 感染治疗的关键词。这篇叙述性综述提供了关于抗生素和非抗生素方法的新数据，重点是针对导致 VAP 的具有临床意义的 GNB 的 3 期试验。

专家意见：头孢他啶-阿维巴坦、美罗培南-瓦波巴坦和亚胺培南-瑞巴坦作为产碳青霉烯酶肺炎克雷伯菌感染的新选择脱颖而出，而头孢洛扎-他唑巴坦为具有多重耐药机制的铜绿假单胞菌感染增加了治疗灵活性。头孢他啶-阿维巴坦和头孢唑烷-他唑巴坦有相关文献。Aztreonam-avibactam 有望用于治疗由产生金属-β-内酰胺酶 (MBL) 的生物体引起的感染。最近批准的cefiderocol具有扩展的抗菌谱，包括KPC-和MBL-生产者。然而，最近公布的数据降低了治疗由耐碳青霉烯鲍曼不动杆菌引起的 VAP 的乐观情绪。. 对于后者，依拉伐环素可能提供额外的希望，等待相关数据。目前被认为是辅助治疗方法的非抗生素治疗是受欢迎的。尽管如此，它们有望在未来替代目前的抗菌药物。