Will new antimicrobials overcome resistance among Gram-negatives?

Abstract

The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, β-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials.

Keywords::

• ESBL
• ESCAPE
• MBL
• new anti-Gram-negative compounds
• new classes of antimicrobials

Financial & competing interests disclosure

Matteo Bassetti serves on scientific advisory boards for Pfizer Inc., Merck Serono, Novartis, Shionogi & Co., Ltd. and Astellas Pharma Inc.; he has received funding for travel or speaker honoraria from Pfizer Inc., Merck Serono, Novartis, GlaxoSmithKline, Gilead Sciences, Inc., Sanofi-Aventis, Cephalon, Inc., Bayer Schering Pharma, Janssen and Astellas Pharma Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.