Optimizing therapy in carbapenem-resistant Enterobacteriaceae infections

In the absence of randomized clinical trial data, questions remain regarding the optimal treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. CRE have historically been susceptible to polymyxins, tigecycline or aminoglycosides (mostly gentamicin), and these antibiotics have long been considered the drugs of choice for CRE infections, although varying rates of resistance to all have been reported. This review looks at data from clinical studies assessing the outcomes of CRE infections treated with different antibiotic regimens.

The recently approved fixed-dose combination agent, ceftazidime-avibactam (CAZ-AVI), is active against KPC and OXA-48-producing Enterobacteriaceae. The limited clinical data available on CAZ-AVI indicate that it is associated with survival benefits relative to other commonly used regimens, although development of resistance is a concern. New drugs active against CRE isolates (including the recently approved meropenem-vaborbactam) are in different stages of development.

CAZ-AVI and meropenem-vaborbactam seem destined to become the backbone of target therapy for high-risk patients with severe infections caused by susceptible CRE strains. However, empirical therapy should be based on risk factors to be defined in the near future, whereas the necessity of combinations with CAZ-AVI requires further studies. Polymyxins are still important options for low-risk patients with susceptible CRE infections, but also for high-risk patients in regions where metallo-β-lactamase-producing CRE predominate because CAZ-AVI and meropenem-vaborbactam are both ineffective against these strains.