Development of antibiotics for Gram-negatives: where now?

Matteo Bassetti, Francesca Ginocchio, Daniele Roberto, Giacobbe, Malgorzata Mikulska

The incidence of infections due to multidrug-resistance pathogens, such as Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter spp. has been increasing. The paucity of antimicrobials active against multidrug-resistance strains are an important challenge. Novel anti-Gram-negative agents from old antimicrobial classes include b-lactamase inhibitors, cephalosporins, carbapenems, aminoglycosides, polymyxin analogs, tetracycline and monobactams. Among them, b-lactamase inhibitors seem the most promising as they might restore the activity of already known b-lactams against b­-lactamase-producing strains. New classes of antimicrobials include bisindoles, boron-containing antibacterial protein-synthesis inhibitors, outer membrane synthesis inhibitors, antimicrobial peptides and antibiotics targeting novel sites of the 50S ribosomal subunit. Although promising, they are still far from being introduced into clinical practice. Therefore, optimizing the use of current antibiotics and infection control policies are mandatory