Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections

Abstract Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial. A rising level of gram-negative resistance has sparked recent interest in novel antibiotic development. Limitations in trial design and translation of trial results into the real-world setting has hindered our response. New, clinician-led approaches are needed to overcome these issues.