Chapter 20: Antimicrobial Drugs

What are antibiotics?Definition: chemicals produced by one

microorganism to kill or inhibit the growth of other microorganisms

Now included the semi-synthetic antibioticsEffective against bacteriaAntibacterial drugs – largest group of

antibioticsGeneral terms used to include other

microbes are antimicrobial drugs or antimicrobials

Difference between disinfectants/antiseptics and antimicrobial drugs

Antibiotic spectrumBroad vs. narrow spectrum

antibioticsBenefits and problems with each

Microbes that produce antibiotics:

Bacteria: Bacillus and Streptomyces

Fungi: Cephalosporium and Penicillium

How do antibiotics work?

1. must kill pathogen and not kill host

2. fewest sides effects in host; highest toxicity in pathogen

3. exploit differences between the pathogen and the host

Modes of action of the antibiotics:1. Inhibition of cell wall synthesis

◦ cell wall is weakened by these when cell is growing

◦ ex. penicillin(s) and cephalosporins◦ low toxicity to humans

Modes of action of the antibiotics:2. Inhibition of protein synthesis

◦ binding to 70S ribosome◦ differences between 70S and 80S

ribosomes◦ ex. chloramphenicol, erythromycin,

streptomycin, tetracyclines◦ host mitochondria may also be affected

 

Modes of action of the antibiotics:3. Increase permeability of plasma

membrane◦ ex. polymyxin B – used topically◦ can have high toxicity in humans◦  

Modes of action of the antibiotics:4. Inhibit synthesis of RNA/DNA

◦ can be very toxic◦ ex. quinolones – DNA

 

Modes of action of the antibiotics:5. Inhibition of metabolic

pathways◦ ex. sulfanilamide – folic acid pathway◦ low toxicity because of the absence of this

pathway in humans

Antagonism vs. synergism of 2 or more antibiotics

Antagonism:◦Ex. Tetracycline penicillin (Why?)

Synergism:◦Ex. TMP-SMZ (SMX) trimethoprim

and sulfamethoxazole

Prophylaxis – preventative use of antibiotics

Ex. of their use:1. before surgery – i.e.

appendix removal

2. before dental work in heart patients

3. in AIDS patients to prevent many infections

Factors affecting antimicrobial activity in vivo –

1. In the environment

A. metabolic state of pathogenEx. Mycobacterium tuberculosis

B. distribution of drug is different in different tissues Ex. blood/brain barrier and necrotic tissue

C. location of pathogen Ex. Chlamydia inside host cells

D. interfering substances Ex. low pH in stomach; binding to proteins in body, etc.

Factors affecting antimicrobial activity in vivo –

2. Concentration of antibiotics in body

A. absorption, inactivation, excretion

B. distribution of the drug – systemic vs. local vs. topical

C. variability – dosing flutuations, how long antibiotic lasts in the body.

Antiviral drugs

Nucleotide analogs (look similar to the bases + sugars of DNA) Ex. AZT – looks like thymine; acyclovir – looks like guanine

Enzyme inhibitors Ex. reverse transcriptase inhibitor – important in controlling HIV infection

Interferons – naturally produced by our immune systemsEx. alpha, beta, and gamma; prevents further infection

Antifungal drugs

Targets for antifungal drugs???Possible side effects???Ex. amphotericin B and

imidazole affect sterol productionGriseofulvin – binds to keratin in

skin cells, treats skin fungal infections

Antibiotic resistance (also called drug resistance)

What is happening?As microbes are exposed to drugs,

the ones with defenses against them survive

Microbial defense mechanisms against antibiotics

1. Change receptor for drug

2. Bind to drug and inactivate it, ex. penicillinase (b-lactamase)

3. Change target site, ex. change ribosome structure

4. Change metabolic pathway

5. MDR pump– multi-drug resistance pump

How does drug resistance develop in different microbes?

Antibiotics overprescribed and not regulatedMany countries do not require a prescriptionImproper dosageAntibacterial soaps/surfaces, etc.Antibiotics in animals (used as our food

source)People insisting on receiving antibiotics,

even for viral infectionsNosocomial infections and the chronically

infected

Antibiotic sensitivity tests

Kirby-Bauer test – zones of inhibition

Minimal inhibitory concentration test

The End