Carbapenemases are bacterial enzymes that break down the carbapenem class of antibiotics. As previously mentioned, these are some of the most powerful and broad-spectrum antibiotics, used for treatment of life-threatening infections and those infections caused by multidrug-resistant nosocomial bacteria. The majority of these carbapenemases are found in Gram-negative bacteria that are not able to catabolize glucose (also known as “non-fermenters“), but a substantial number have been incorporated within the chromosomal and mobile genetic elements of Enterobacteriaceae. An incomplete list of these carbapenemases are displayed in the Table below, the primary source of which is A/Prof Koh Tse Hsien‘s NUS PhD thesis.

Carbapenemases in Enterobacteriaceae - including those isolated in Singapore
Carbapenemases in Enterobacteriaceae – including those isolated in Singapore

The major “epidemic” or widely-disseminated carbapenemases are highlighted in bold in the Table – all of these are found in plasmids, which are mobile genetic elements with pieces of DNA (virtually always circular) found in bacteria that are able to replicate independently of the host bacterium’s chromosomal DNA. There are significant differences in the way that these carbapenemases are spread, however, which are probably largely because of the properties of the plasmids that carry these carbapenemase genes. These differences are probably best conceived and understood in relation to the currently popular operating systems of mobile devices – iOS and Android.

The "iOS" and "Android" models of the spread of various carbapenemases
The “iOS” and “Android” models of the spread of various carbapenemases

The NDM gene – since it’s discovery in 2010 – is found on plasmids that are easily transferrable between bacteria, and has therefore been found in multiple types of bacteria, including non-fermenting Gram-negative bacteria. The bacteria that carry the NDM gene and its plasmid are seldom epidemic clones of bacteria – i.e. widepread and successful bacterial clones. In contrast, the plasmids carrying the KPC gene, and to a lesser extent the OXA carbapenemases, are less easily transferred between bacteria and bacterial species. Their rapid dissemination throughout the world has been linked to the spread of very successful epidemic clones of Klebsiella pneumoniae and Escherichia coli, although they have also been found in non-epidemic bacterial clones (no analogy is perfect!).

Currently, the most common carbapenemases found in Enterobacteriaceae from Singapore hospitals are NDM-1 and KPC, followed distantly by OXA-type carbapenemases (OXA-48 and OXA-181).