Clinical Pharmacokinetics and Pharmacodynamics of Imipenem-Cilastatin/Relebactam Combination Therapy.

On 16 July, 2019, the US Food and Drug Administration approved imipenem-cilastatin/relebactam (Recarbrio™) for the treatment of adults with complicated urinary tract infections and complicated intra-abdominal infections. This decision was based on substantial clinical and pre-clinical data, including rigorous pharmacokinetic and pharmacodynamic work, and is an important step forward in the management of these debilitating conditions. This article provides an overview of the body of research associated with imipenem-cilastatin/relebactam, beginning with an examination of the fundamental underpinnings of the pharmacokinetic/pharmacodynamic index. This is followed by the pharmacokinetic/pharmacodynamic work that led to the approval of this novel drug combination, including data derived from checkerboard and hollow fiber infection studies, as well as large, multi-center, phase III clinical trials known as RESTORE-IMI 1 and RESTORE-IMI 2. The article also explores how this important new antibiotic may be used to treat other infections in the years to come, including hospital-acquired bacterial pneumonia and ventilator-associated pneumonia attributed to imipenem-non-susceptible pathogens and certain atypical mycobacterial infections.