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