Gram-negative bacteriae with resistance to carbapenems

Clinically-significant Gram-negative species remain mostly Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Carbapenem molecules are often the last resort for treating infections due to multidrug resistant isolates. In Enterobacteriaceae, resistance to carbapenems may result from combined mechanisms of resistance associating b-lactamases with weak (if any) intrinsic carbapenemase activity and decreased outer membrane permeability, or from true carbapenemases. KPC-type enzymes (partially inhibited by clavulanic acid) have been identified mostly in Klebsiella pneumoniae, first in bacteria identified in the USA and then worldwide, and in many enterobacterial species. Carbapenem-hydrolyzing b-lactamases (CHBL) could be also metallo-b-lactamases (VIM, IMP, NDM-1, etc.) mostly in hospital-acquired K. pneumoniae. One of the latest reported CHBL in Enterobacteriaceae is OXA-48, identified mostly in Mediterranean countries. All these carbapenemase producers are difficult to detect in a clinical laboratory and may be the source of multidrug resistance leading to a therapeutic dead end. Whereas the main mechanism of resistance to imipenem in P. aeruginosa remains due to a modification of the outer membrane protein OprD, the landscape of CHBL in P. aeruginosa expanding worldwide is made of KPC, GES-related enzymes and metallo-b-lactamases (IMP, VIM, etc.). These enzymes are involved in multidrug resistance strains as a source of nosocomial outbreaks. In Acinetobacter baumannii, KPC and metallo-b-lactamases have been identified. However, the most frequent CHBL are oxacillinases (OXA-23, OXA-40, OXA-58, OXA-143) which are specific to that species. Novel carbapenemases are continuously being identified worldwide with exchange of the resistance genes between Enterobacteriaceae, P. aeruginosa and A. baumannii.