Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?

Expert Opinion on Pharmacotherapy
Federico PerezRobert A Bonomo

Abstract

For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered 'old' antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containing a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic ap...Continue Reading

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