Why we cannot give Bacteriocidal and Bacteriostatic antibiotics together? |Pharmacology|


image

Ok, now let us take a little bit of time to squeeze our head and try to figure out the answer- Why we cannot give bacteriocidal and bacteriostatic antibiotics together?

Let us do some quick revision on the fundemental knowledge of antimicrobial therapy

Bacteriostatic – These agents do not kill the bacteria but rather stopping it from replicating to produce more progeny bacteria such as by interrupting protein sythesis
Example :-
Choramphenicol
Tetracycline
Macrolides

Bacteriocidal – These agents can simply kill the bacteria by disrupting the intergrity of cell wall; peptidoglycan
Example :-
Penicillin
Cephalosporin
Carbapenem
Monobactam
Glucopeptide

Lets see, what if I give Tetracycline (bacteriostatic) together with Penicillin (bacteriocidal)? What will happen? Are they synergizing each other, or antagonizing each other?
Ok, let us take one step at a time; we try to enumerate the mechanism of action of Tetracycline and Penicillin separately

Tetracycline
1) It acts by inhibiting 50S ribosomal subunit and inhibiting the binding of tRNA to the A site on the 30s ribosomal subunit.

2) As we all clear, protein synthesis is crucial for cell to replicate as it needs to double it’s cellular components in order to divide into 2 progeny cells.

3) When protein synthesis is halted, cell doesn’t have enough protein to get ready for replication. Thus, it wont divide

4) So, the bacteria remains dormant and eventually weakens and make it easy to be destroyed by immune cells.

Penicillin
1) I do realize that we all know that there are extensive subgroup of penicillin such as methicillin, amoxycillin and etc, but let us take it as a whole.

2) It acts by inhibiting the cross linking of nascent (NEW) peptidoglycan through binding to Penicillin Binding Protein (PBP).

3) It must be clear that cross linking only happens when there is a NEWLY synthesized peptidogycan

4) Ting Tong! Ok, lets see, peptidoglycan can only be synthesized when the cell is starting to replicate. Of course it needs new peptidoglycan, cause it needs to divide into two, remember? If not, there wont be enough peptidoglycan for the cell to give rise to 2 progeny cells

Ok, now let us get back to our 1 billion dollar question – Why we cannot give bacteriostatic together with bacteriocidal antibiotics?

If you give Tetracycline, it will eventually stop bacterial replication.
Without replication, there will be no synthesis of new peptidoglycans.

Without new peptidoglycans, there will be no cross linking.

Without cross linking, Penicillin couldn’t elicit its response.

So, we can see there is an antagonism happening between Tetracycline and Penicillin.
Different author has different opinion, but most of them believed that Tetracycline reduces Penicillin action into half.
Therefore, Tetracycline and Penicillin are said to be antagonizing with each other.

In what condition does antibiotics give synergistic effect between each other?

Let me put it in a simple way, synergism only happens when we give two antibiotics which have different mechanism of actions but lead to same final result.
Let me give a very popular example of synergism in antibiotic therapy = Bactrim® (Sulfamethoxazole plus Trimethoprim)

1) Both Sulfamethoxazole and Trimethoprim are folate synthesis inhibitor

2) Sulmathoxazole is a false substrate of Dihydropteroate Synthatase. It acts by competitivey inhibiting the enzyme. Inhibition of this enzyme will reduce the production of Dihydrofolate Reductase which is essential in synthesizing Tetrahydrofolic Acid.

3) Trimethoprim on the other hand, inhibits the Dihydrofolate Reductase itself. Thus inhibits the production of Tetrahydrofolic Acid.

4) So, we get it now! Both antibiotics will ultimately reduce the production of Tetrahydrofolic Acid. It must be clear that bacteria cannot take folic acid from the environment, it solely depends in de novo folic acid. Inhibition of production in Tetrahydrofolic Acid will stop replication cause folic acid is precursor to DNA nucleosides. Eventually bacteria will starve and unable to replicate.

5) See, both inhibit different enzymes but ultimately leads to same final result which is the reduction in production of Tetrahydrofolate Acid.

6) Bactrim® successfully use in the treatment of
Respiratory tract infection
Urinary tract infection
Gastrointestinal tract infection

Thats all from me for today, hope it helps you people =) Goodluck by the way

Advertisements

13 responses to “Why we cannot give Bacteriocidal and Bacteriostatic antibiotics together? |Pharmacology|

  1. but i’ve read that penicillins are synergistic with aminoglycosides as penicillins are cell wall inhibitors so they alter the permeability of the cell wall and enhance the entry of the aminoglycosides ??

    • Yes, that’s because amino glycosides act at a different site on the bacterial cell than the penicillins do. Aminoglycosides kill by inhibiting bacterial protein synthesis and penicillins kill by cell wall formation inhibition. One breaks down the wall to allow/aid the other to get to the ribosome in the cell and mess up bacterial protein formation. It’s a different scenario to combining tetracyclines and penicillin as they are different classes of antibiotic, and both are cidal as opposed to the latter combo (one cidal and one static). Penicillins act on fast growing bacteria, and if you use a static drug (tetracyclines) that halts growth and ‘renders it powerless’.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s