New strategies and structural considerations in development of therapeutics for carbapenem-resistant Enterobacteriaceae

Antimicrobial resistance poses a significant threat to our ability to treat infections. Especially concerning is the emergence of carbapenem-resistant Enterobacteriaceae (CRE). In the new 2019 United States Centers for Disease Control and Prevention Antibiotic Resistance Report, CRE remain in the most urgent antimicrobial resistance threat category. There is good reason for this concerning designation. In particular, the combination of several resistance elements in CRE can make these pathogens untreatable or effectively untreatable with our current armamentarium of anti-infective agents. This article reviews recently approved agents with activity against CRE and a range of modalities in the pipeline, from early academic investigation to those in clinical trials, with a focus on structural aspects of new antibiotics. Another article in this series addresses the need to incentive pharmaceutical companies to invest in CRE antimicrobial development and to encourage hospitals to make these agents available in their formularies. This article will also consider the need for change in requirements for antimicrobial susceptibility testing implementation in clinical laboratories to address practical roadblocks that impede our efforts to provide even existing CRE antibiotics to our patients.