Management of Highly Resistant Gram-Negative Infections in the Intensive Care Unit in the Era of Novel Antibiotics

Antimicrobial-resistant bacterial infections, particularly those caused by Gram-negative bacteria, are major public health threats globally. Since 2015, several antibiotics with activity against highly antimicrobial-resistant Gram-negative bacteria have been approved, which offer alternatives emerging to previous frontline agents such as polymyxins and aminoglycosides. Despite data that new drugs are more effective and better tolerated than older agents against at least some highly antimicrobial-resistant Gram-negative bacterial infections, clinicians remain uncertain about how best to incorporate them into clinical practice. In this article, we discuss the management of highly resistant Gram-negative bacterial infections in the era of new antibiotics, with particular attention to those caused by AmpC- and extended-spectrum β-lactamase-producing Enterobacterales (which manifest phenotypically as 3rd generation cephalosporin resistance), carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant acinetobacter baumannii, and Stenotrophomonas maltophilia.