Where do carbapenems originate from?
Carbapenems originate from a naturally occuring chemical substance called thienamycin, a compound derived from the bacterium Streptomyces cattleya. Thienamycin is likely to have been in existence for millions of years.
What is the mechanism of their anti-bacterial activity?
Carbapenems are beta-lactam antibiotics therefore prevent peptidoglycan crosslinking in cell wall formation.
What carbapenems are used in clinical practice?
The most common carbapenems used in clinical practice (and approved by the FDA) are imipenem, meropenem, ertapenem and doripenem, Each have subtle differences. There are a few other less common ones around.
Are the commercially available carbapenems used orally?
No they are all only available as intra-venous preparations. Researchers are trying to develop an oral carbapenem.
What bacteria are inherently resistant to carbapenems?
Carbapenems have no activity against MRSA (Methicillin Resistant Staphylococcus aureus) or Stenotrophomonas maltophilia. Use of carbapenems has therefore the risk of selecting out such organisms (along with candida species).
Are carbapenems affected by AmpC or CTX type ESBLs?
No, carbapenems maintain activity against these particular resistance enzymes.
What mechanisms can bacteria use to acquire resistance to carbapenemases.
Bacteria may acquire resistance to carbapenems by altering their porin surface receptors, thus restricting entry of the carbapenems. Alternatively some are able to to upregulate efflux pumps to remove carbapenems from the bacterium. Enterobacteriaciae may also produce enzymes that are capable of hydrolysing carbapenems (as well as all other beta-lactams) called carbapenemases. Most carbapenemases seem to derive from environmental Bacillus species. Again, these resistance enzymes have probably been around for millions of years.
To study carbapenemases in more detail, click here for an excellent review on carbapenemases.
What does the acronym NDM stand for?
New Dehli Metallo-Beta-Lactamase is a type of carbapenemase which has received recent media attention and is relatively common in some parts of the world.
What is the Hodge test?
The Hodge test is a phenotypic test for detection of carbapenemases in the laboratory. There are also genotypic tests available for most of the common carbapenemases.