Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections

Abstract

Microbial resistance is a serious threat to human health worldwide. Among the World Health Organisation's list of priority resistant bacteria, three are listed as critical-the highest level of concern-and all three are Gram-negative. Gram-negative resistance has spread worldwide via a variety of mechanisms, the most problematic being via AmpC enzymes, extended-spectrum β-lactamases, and carbapenemases. A combination of older drugs, many with high levels of toxicity, and newer agents are being used to combat multidrug resistance, with varying degrees of success. This review discusses the current treatments for multidrug-resistant Gram-negative bacteria, including new agents, older compounds, and new combinations of both, and some new treatment targets that are currently under investigation.

Figure 1.

Suggested treatments for carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter baumannii.^, Treatment choice in each case should also depend on local epidemiology and bacterial susceptibility, and any potential additional toxicity when combining therapy. BL/BLI, β-lactam/β-lactamase inhibitor; KPC, Klebsiella pneumoniae carbapenemase; MDR, multidrug-resistant.