Now, I’d like to bring you onto the final
slide for this lecture series which deals
Here we have the... a model structure of a
carbapenem. You should be able to identify
some of the core components being very similar
to the penicillins we’ve discussed thus
We have the beta-lactam ring, the core component
required for inhibition of the penicillin-binding
protein. We also have a five-membered ring
which has increased ring strain. This is imparted
by the addition of a double bond which forces
the stereochemistry to be less thermodynamically
stable. But, crucially, I’d like to draw
your attention to the inverted stereochemistry.
Carbapenems have the broadest spectrum of
all of the beta-lactam antibiotics, working
on Gram-negative bacterial infections and
Gram-positive bacterial infections and are
often the last line of defence for a systemic
infection in the context of beta-lactam antibiotics.
But, where they’re particularly useful is
their resistance to lactamase activity. So,
whereas we before had the problem where we
have penicillin-resistant bacteria because
they produce a beta-lactamase that breaks
open that lactam ring rendering the penicillin
antibiotic null and void, here we have a class
of beta-lactam which, by virtue of the inverted
stereochemistry in the sixth position, actually
is resistant to the actions of lactamase.
If you recall, the original structure of penicillin
showed a relative cis-orientation of the two
hydrogens in alpha and beta positions on the
lactam ring. Here we see, however, there is
a relative trans-orientation on those hydrogens
with, in this case, our substituted methyl
group pushing backwards rather than forwards.
And this is what conveys that resistance to
lactamases produced by the bacteria and makes
this a really, really effective beta-lactam
antibiotic, working with strains that are
often quite resistant to a treatment with
other penicillins. This works particularly
However, what we are now seeing, and this
is something to bear in mind, is the rise
of bacteria which produce an enzyme called
carbapenemase. This enzyme carbapenemase can
actually selectively break down the beta-lactam
ring in a carbapenem. And this is cause for
increasing concern since, if we are unable
to actually treat infections and so forth
with carbapenem because of the rise of carbapenemase-producing
bacteria, then even routine operations could
become quite dangerous.
I’d like to thank you for bearing with me
throughout the course of this module and also
for your attention throughout this course.
Thank you very much.