Double- and multi-carbapenemase-producers: the excessively armored bacilli of the current decade

摘要

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative nosocomial pathogens commonly carry one carbapenemase gene conferring resistance to carbapenems and other beta-lactam antibiotics. However, increasing reports show that double-carbapenemase-producing (DCP) and even multi-carbapenemase-producing (MCP) bacteria are emerging in some parts of the world, diminishing further, in some cases, the already limited treatment options. In the present review, the up-to-date reports of DCP and MCP isolates are summarized and concerns regarding their emergence are discussed. Carbapenems are the most important beta-lactam antibiotics, presenting an exceptionally broad spectrum of activity, while, at the same time, being less vulnerable to beta-lactam-hydrolyzing enzymes, including the extended-spectrum beta-lactamases (ESBLs). Resistance to these agents in Gram-positives is known to be mediated by mutation-derived changes of penicillin-binding proteins (PBPs). Carbapenem resistance in Gram-negative bacteria on the other hand, is due to carbapenemase production, diminished outer membrane permeability, efflux pumps over-expression, or a combination of the aforementioned mechanisms.