00:00
Other approaches to the problems of bacteria
producing these beta-lactamases, which go
onto inhibit antibiotics, involves the use
of a sacrificial compound which can be given
or co-administered with penicillins to treat
penicillin-resistant bacteria. An example
of this is clavulanic acid.
00:22
Clavulanic acid is a structure shown here
has remarkable similarity to penicillin as
you can appreciate: has the beta-lactam ring,
okay? It doesn’t have the thiazolidine ring,
but what it does have is the ability to interact
directly with beta-lactamases. So, if you
have a beta-lactamase-producing bacteria,
which under normal circumstances would mean
that it would be resistant to the penicillin
that you would administer, you can co-administer
this clavulanic acid and use it as a sacrificial
compound so that it occupies and irreversibly
binds to the beta-lactamase produced. This
means that there is insufficient beta-lactamase
around to then react with the penicillin that
you’ve just administered which you want
to work.
01:13
So, the reason that this is used is because,
in of itself, it is not an antibiotic, but
it irreversibly binds to the beta-lactamase
and prevents it from breaking down, therefore,
penicillins that you’ve administered. Standard
names for these co-administered antibiotics
would be things like amoxiclav, a mixture
of amoxicillin and clavulanic acid.
01:36
Now, I want to just briefly talk to you about
another class of beta-lactam antibiotics which
relates to the penicillins we’ve just discussed
and they are the cephalosporin class.
01:48
They have been found to be generally more
resistant to acid hydrolysis and also generally,
more resistant to beta-lactamase produced
by bacteria which have this grown resistance.
02:04
As you can see, there’s a slightly different
way in which they work, but they both or they
all have this characteristic beta-lactam four-membered
ring system.
02:14
In this scenario, the serine represented here
of the active site of the penicillin-binding
protein is shown as a line with OH coming
out of it. The lone pair of electrons on the
oxygen attacks the carbonyl-carbon, opens
it up and cleaves the beta-lactam ring forming,
as you can see, an ester bond. There is an
entropically driven part for this mechanism
which is the loss of an acetate group, as
you can clearly see at the other end of this
six-membered ring.
02:46
Cephalosporin C, as you can see here, which
is one of the first-generation of cephalosporin-based
antibiotics, has evenly-distributed Gram-negative
and Gram-positive activity. So, generally
speaking, this was a subsequent development
improvement on the penicillin class using
this six-membered ring cephalosporin class.