Saturday, June 2, 2018

So, this post is about our chemotherapy question posted on facebook page.

Question is as follow

Time dependant killing and prolonged post-antibiotic effect is seen with:

1) Fluoroquinolones.
2) Beta-Lactam antibiotics.
3) Clindamycin.
4) Erythromycin.

Answer is 2- Beta lactam antibiotics

Okay, so let's get started.

Today we will learn about three simple and basic concepts of the chemotherapy.

1) Concentration dependent killing:
The killing effect of a drug is high when ratio of peak concentration to MIC(Minimum inhibitory concentration) is more.

Simplified version:
Suppose drug called as "A" kills a particular bacteria.
Now I am going to put 2 units of this drug in a medium containing that bacteria for 10 minutes. After 10 minutes when I check the medium I still find the living bacteria present. I wait for another 10 minutes. After total 20 minutes I recheck it - I still find living bacteria!

Now, I change the concentration of the drug "A" to 4 units but keeping the time same i.e. 10 minutes. Now, when I check the medium for bacteria after 10 minutes  I find dead bacteria. This means that antibiotic dose of 4 units is needed minimum for killing the bacteria irrespective of the time.

In a nutshell: These drugs need one large dose for their action rather than  multiple small doses

Drugs having CDK:
Mnemonics: CAFe

C=CDK
A= Aminoglycosides
F=Fluoroquinolones

2) Time dependant killing( TDK) :
This means the antimicrobial action depends on the length of time the concentration remains above MIC.

Simplified version:
Let's take the same example.

Now, "2 units" of drug A is kept for 10 minutes in a medium containing particular bacteria. After 10 minutes I check the medium and I find living bacteria. I add 2 units more and I wait for another 10 minutes like I did previously. But this time after total of 20 minutes I find dead bacteria!

Now, I again do this experiment but this time with 4 units of drug A.
I wait for 10 minutes
Result: Living bacteria
I wait for another 10 minutes( Total =20 minutes) without adding any further dose.

In a nutshell: In TDK, multiple doses are preferred over single dose!

Drugs having TDK:
Mnemonics : T.V. Box.

T= TDK
V=Vancomycin
B= Beta-Lactams

3) Post antibiotic effect (PAE):

After an organism is exposed to antibiotic, it's growth stops. When it is put in antibiotic free medium, the growth resume after sometime.
This is called as PAE.

PAE is seen when antibiotic concentration is below MIC.

Drugs showing PAE:
Most of the antimicrobials have long PAE against gram positive bacteria.

Drugs showing PAE against gram negative bacteria:
Mnemonic- CPD(cephalo-pelvic disproportion) nurse.

C= Carbapenems
P= Protein synthesis affecting drugs(Aminoglycosides, chloramphenicol, tetracyclines)
D= DNA synthesis affecting drug ( Quinolones, rifampicin)

N= Negative bacteria

Points to remember:

1) Rifampicin prolongs the PAE of isoniazid.
2) Macrolides and clindamycin also possess time dependent activity. However they are static drugs so we cannot use TDK term for them.