1. Chapter 20: Antimicrobial Drugs

2. What are antibiotics?
Definition: chemicals produced by one microorganism to kill or inhibit the growth of other microorganisms
Now included the semi-synthetic antibiotics
Effective against bacteria
Antibacterial drugs – largest group of antibiotics
General terms used to include other microbes are antimicrobial drugs or antimicrobials
Difference between disinfectants/antiseptics and antimicrobial drugs

3. Antibiotic spectrum Broad vs. narrow spectrum antibiotics
Benefits and problems with each

5. Microbes that produce antibiotics:
Bacteria: Bacillus and Streptomyces
Fungi: Cephalosporium and Penicillium

7. 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

9. 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

11. 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

13. Modes of action of the antibiotics:
3. Increase permeability of plasma membrane
ex. polymyxin B – used topically
can have high toxicity in humans

15. Modes of action of the antibiotics:
4. Inhibit synthesis of RNA/DNA
can be very toxic
ex. quinolones – DNA

17. 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

19. Antagonism vs. synergism of 2 or more antibiotics
Ex. Tetracycline  penicillin (Why?)
Synergism:
Ex. TMP-SMZ (SMX) trimethoprim and sulfamethoxazole

20. 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

21. Factors affecting antimicrobial activity in vivo –
In the environment
A. metabolic state of pathogen
Ex. 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.

22. Factors affecting antimicrobial activity in vivo –
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.

23. 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

25. Antifungal drugs Targets for antifungal drugs???
Possible side effects???
Ex. amphotericin B and imidazole affect sterol production
Griseofulvin – binds to keratin in skin cells, treats skin fungal infections

26. Antibiotic resistance (also called drug resistance)
What is happening?
As microbes are exposed to drugs, the ones with defenses against them survive

27. Microbial defense mechanisms against antibiotics
Change receptor for drug
Bind to drug and inactivate it, ex. penicillinase (b- lactamase)
Change target site, ex. change ribosome structure
Change metabolic pathway
MDR pump– multi-drug resistance pump

28. How does drug resistance develop in different microbes?
Antibiotics overprescribed and not regulated
Many countries do not require a prescription
Improper dosage
Antibacterial soaps/surfaces, etc.
Antibiotics in animals (used as our food source)
People insisting on receiving antibiotics, even for viral infections
Nosocomial infections and the chronically infected

31. Antibiotic sensitivity tests
Kirby-Bauer test – zones of inhibition
Minimal inhibitory concentration test

35. The End