Antimicrobial Drugs

11 May 2013

Antimicrobial Drugs
Chemotherapy
The use of drugs to treat a
disease
Antimicrobial drugs
Interfere with the
growth of
microbes within a host
Antibiotic
Substance produced by a
microbe that, in small amounts,
inhibits
another microbe
Selective toxicity A drug that kills harmful
microbes
without damaging the host

 1928 Fleming
discovered
penicillin,
produced by
Penicillium.
1940 Howard
Florey and Ernst
Chain performed
first clinical trials
of penicillin.
All three were
awarded the
Nobel Prize in
Medicine in 1945

Figure 20.1

Many Antibiotics come from Bacterial or Fungal Sources

Table 20.1

Table 20.2

The Action of Antimicrobial

Drugs
Disrupt Cell Wall synthesis or through
damage
Disrupt Proteins synthesis
Disrupt Nucleic Acid synthesis or
function
Disrupts essential metabolic
enzymes-usually by competitive
inhibition.

The Action of Antimicrobial

Drugs

Figure 20.2

The Action of Antimicrobial

Drugs

Figure 20.4

Penicillins

Figure 20.6

Penicillinase Enzyme Allows

Bacteria to be Resistant to
Penicillin

Figure 20.8

Other Inhibitors of Cell Wall

Synthesis
Cephlosporins-used Penicillin structure to
synthesize antibiotics more effective on Gram
Negative bacteria
Polypeptide antibiotics
Bacitracin
Topical application
Against gram-positives

Vancomycin
Glycopeptide
Important "last line" against antibiotic resistant S. aureus

Other Inhibitors of Cell Wall

Synthesis

Antimycobacterium antibiotics (TB, Leprosy)

Isoniazid (INH)
Inhibits mycolic acid synthesis

Ethambutol
Inhibits incorporation of mycolic acid

Inhibitors of Protein Synthesis

Chloramphenicol
Broad spectrum
Binds 50S subunit, inhibits peptide bond
formation

Aminoglycosides
Streptomycin, neomycin, gentamycin
Broad spectrum
Changes shape of 30S subunit

Inhibitors of Protein Synthesis

Tetracyclines
Broad spectrum
Interferes with tRNA attachment

Erythromycin
Gram-positives
Binds 50S, prevents translocation

Injury to the Plasma

Membrane

Polymyxin B

Topical
Combined with bacitracin and neomycin
in over-the-counter preparation

Inhibitors of Nucleic Acid

Synthesis

Rifamycin

Inhibits RNA synthesis

Antituberculosis

Quinolones and fluoroquinolones

Ciprofloxacin
Inhibits DNA gyrase
Urinary tract infections

Competitive Inhibitors
Sulfonamides (Sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum

Figure 5.7

Figure 20.13

Antifungal Drugs
Inhibition of Ergosterol
Synthesis

Ergosterol important part of fungal

cell wall. Unique to fungi, therefore a
good drug target

Inhibition of Cell Wall

Synthesis

Echinocandins
Inhibit synthesis of -glucan

Antifungal Drugs
Inhibition of Nucleic Acids

Flucytocine

Cytosine analog interferes with RNA

synthesis

Antifungal Drugs
Inhibition of Microtubules
(Mitosis)

Tolnaftate

Used for athlete's foot; action unknown

Antiviral Drugs
Nucleoside and Nucleotide
Analogs

Figure 20.16a

Antiviral Drugs
Nucleoside and Nucleotide
Analogs

Figure 20.16b,
c

Antiviral Drugs: Enzyme

Inhibitors

Protease inhibitors
Indinavir
HIV

Inhibit attachment
Zanamivir
Influenza

Antiprotozoan Drugs
Chloroquine
Inhibits DNA synthesis
Malaria

Antibiotic Resistance
A variety of mutations can lead to antibiotic
resistance.
Mechanisms of antibiotic resistance
1.
2.
3.
4.

Enzymatic destruction of drug

Prevention of penetration of drug
Alteration of drug's target site
Rapid ejection of the drug

Resistance genes are often on plasmids or

transposons that can be transferred between
bacteria.

Antibiotic Resistance
Misuse of antibiotics selects for
resistance mutants. Misuse includes:
Using outdated, weakened antibiotics
Using antibiotics for the common cold and
other inappropriate conditions
Use of antibiotics in animal feed
Failure to complete the prescribed regimen
Using someone else's leftover prescription

Disk-Diffusion Test

Figure 20.17

Chemical Methods of
Microbial Control

Evaluatingadisinfectant

Diskdiffusionmethod

Figure 7.6

 MIC
MBC

Minimal inhibitory concentration

Minimal bactericidal concentration

E Test

Figure 20.18

Effects of Combinations of
Drugs
Synergism occurs when the effect of two drugs
together is greater than the effect of either alone.
Antagonism occurs when the effect of two drugs
together is less than the effect of either alone.

Effects of Combinations of
Drugs

Figure 20.22

The Future of
Chemotherapeutic Agents
Antimicrobial peptides
Broad spectrum antibiotics from plants and
animals
Squalamine (sharks)
Protegrin (pigs)
Magainin (frogs)

Antisense agents
Complementary DNA or peptide nucleic
acids that binds to a pathogen's virulence
gene(s) and prevents transcription