Status report on carbapenemases: challenges and prospects

Abstract

Antimicrobial resistance in hospital and community-onset bacterial infections is a significant source of patient morbidity and mortality. In the past decade, we have witnessed the increasing recovery of carbapenem-resistant Gram-negative bacteria. For many isolates, carbapenem resistance is due to the production of carbapenemases, β-lactamases that can inactivate carbapenems and frequently other β-lactam antibiotics. Currently, these enzymes are mainly found in three different β-lactamase classes (class A, B and D). Regardless of the molecular classification, there are few antimicrobials available to treat infections with these organisms and data regarding agents in development are limited to in vitro studies. This article focuses on the epidemiology of carbapenemase-producing Gram-negative bacteria. We also review available agents and those in development with potential activity against this evolving threat.

Keywords::

• antibiotic resistance
• carbapenemase
• carbapenem resistant
• Gram negative
• KPC
• MBL
• metallo-β-lactamases
• NDM-1
• oxacillinase

Financial & competing interests disclosure

Robert A Bonomo is supported by research grants from the National Institutes of Health (RO1 A1072219), the Veterans Affairs Merit Review Program, Achogen, and Pfizer. Robert A Bonomo is also supported by the VISN 10 GRECC. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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