Carbapenem-Hydrolyzing Gram-Negative Bacteria: Current Options for Treatment and Review of Drugs in Development

Foad I. Abandeh, Mark E. Drew, Madhuri M. Sopirala

doi:10.2174/157489112799829675

Abstract

Multidrug resistant gram-negative bacteria are an increasing therapeutic challenge. The beta-lactamases are a group of enzymes that confer resistance to the beta-lactam antibiotics. The carbapenems have been in wide use to treat beta-lactamase producing, multidrug resistant gram-negative bacterial infections. However, the emergence of carbapenemases, enzymes capable of hydrolyzing the carbapenems, has limited our therapeutic options. In the recent years, there has been some development in the discovery of new agents such as boronic acid derivatives, ME1071 and Ca-EDTA that may enhance the activity of existing antibiotics, CTC-96 which reverses antibiotic resistance and polymyxin derivatives with decreased renal toxicity. While global efforts towards new drug development should continue, appropriate use of currently available antibiotics is equally important. In this review, we will discuss the general characteristics of carbapenemases, recent patents with drugs under development and current treatment options.

Keywords: Beta-lactamases, carbapenemases, gram-negative bacteria, multidrug resistant, novel agents, patent, Klebsiella pneumoniae, Aminoglycosides, Fosfomycin, Antimicrobial Combination Therapy