Carbapenems are considered as last-resort
antibiotics for the treatment of
infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of
carbapenems in clinical practice, the emergence of
carbapenem-resistant pathogens now poses a great threat to human health. Currently,
antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with
polymyxins,
tigecycline,
fosfomycin, and
aminoglycosides as the mainstays of
therapy. The need for new and effective anti-CRE
therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE
infections, including high-dose
tigecycline, high-dose prolonged-infusion of
carbapenem, and double
carbapenem therapy. We also review the newly available
antibiotics which have potential in the future treatment of CRE
infections:
ceftazidime/avibactam, which is active against KPC and OXA-48 producers;
meropenem/vaborbactam, which is active against KPC producers;
plazomicin, which is a next-generation
aminoglycoside with in vitro activity against CRE; and
eravacycline, which is a
tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new
antibiotics provide additional therapeutic options for CRE
infections. Finally, we review other potential anti-CRE
antibiotics in development:
imipenem/
relebactam and
cefiderocol. Currently, high-dose and combination strategies that may include the new β-
lactam/β-lactamase inhibitors should be considered in severe CRE
infections to maximize treatment success. In the future, when more treatment options are available,
therapy for CRE
infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for
infections caused by CRE.