We agree with, and would like to further elaborate on, Simone Lanini and colleagues' proposal to use adaptive randomised controlled trials to improve research on infections with carbapenem-resistant Gram-negative bacteria. The efficacy of ceftazidime–avibactam for infections with carbapenem-resistant Gram-negative bacteria has only been assessed in observational studies,^,  leaving several important real-world questions unanswered. First, is it preferable to use ceftazidime–avibactam in monotherapy or in combination therapy, and in case of the latter, what is the most effective combination therapy? Second, should ceftazidime–avibactam be administered in continuous or intermittent infusion? Finally, do specific populations require targeted dosing schedules? To address these questions with adaptive randomised controlled trials, we propose three scenarios in which clinical questions are explored through different adaptive designs ().

中文翻译：

---

新型抗微生物药对耐碳青霉烯，革兰氏阴性细菌感染的适应性试验。

我们同意并希望进一步阐述西蒙娜·兰尼尼（Simone Lanini）及其同事的建议，即使用适应性随机对照试验来改善对耐碳青霉烯类革兰氏阴性菌感染的研究。仅在观察性研究中评估了头孢他啶-avibactam对耐碳青霉烯的革兰氏阴性菌感染的功效^， 留下了一些重要的现实世界问题。首先，将头孢他啶-阿维巴坦用于单药治疗或联合治疗是否更可取；对于后者，哪种疗法最有效？第二，头孢他啶-阿维巴坦应连续或间歇输注吗？最后，特定人群是否需要有针对性的给药时间表？为了通过自适应随机对照试验解决这些问题，我们提出了三种方案，其中通过不同的自适应设计来探索临床问题。