Mechanisms of carbapenem resistance (page under construction)
Klebsiella pneumonia carbapenemase
There are several mechanisms of carbapenem resistance. One of the most epidemiologically concerning mechanisms is the emergence of enzymes (carbapenemases) capable of degrading carbapenems and beta-lactams more generally. Amongst these, Klebsiella pneumonia carbapenemases or KPCs for short have made the greatest inroads in the United States. First identified retrospectively from a 1996 sample from North Carolina, they have since spread and become endemic in New York City and now many other locations in the United States and around the world. These "Class A" serine-based hydrolytic enzymes are for the most part encoded on large, low copy number plasmids. Such large plasmids often employ conjugation machinery to promote transfer of the plasmid and plasmid-borne resistance elements into different bacterial populations. At present, KPC's are predominantly associated with Klebsiella pneumonia (hence their name) and Escherichia coli. KPC strains are notoriously difficult to treat, as they often display broad spectrum resistance to many other antimicrobials including aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole.