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Chapter 20: Antimicrobial Drugs

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Title: Chapter 20: Antimicrobial Drugs


1
Chapter 20 Antimicrobial Drugs
2
Antimicrobial Drugs
  • Chemotherapy The use of drugs to treat a
    disease
  • Antimicrobial drugs Interfere with the growth of
    microbes within a host

3
  • Antibiotic Substance produced by a microbe
    that, in small amounts, inhibits another microbe

Table 20.1
4
www.textbookofbacteriology.net
5
  • 1928 Fleming discovered penicillin, produced
    by Penicillium (mold)
  • First clinical trials in early 1940s

Figure 20.1
6
Broad-spectrum antibiotics those that affect a
broad range of gram-positive and/or gram-negative
bacteria
Table 20.2
7
Antimicrobial Drugs Selective Toxicity
  • Selective toxicity property of a drug that
    allows it to kill microbes without damaging the
    host cells
  • Takes advantage of differences in cell structure
    and metabolism between the microbe and host cells
  • Antibacterials target prokaryotic structures
  • Penicillin prevents proper synthesis of
    peptidoglycan

8
The Action of Antimicrobial Drugs
  • Bactericidal causes death of bacteria
  • Bacteriostatic prevents growth of bacteria

9
Targets of Antimicrobial Drugs
Figure 20.2
10
Targets of Antimicrobial Drugs Cell wall
synthesis
  • Penicillin weakens bacterial cell walls by
    inhibiting the crosslinking of peptidoglycan
  • Peptidoglycan is found only in bacterial cell
    walls
  • Bactericidal (must be actively growing)

11
Targets of Antimicrobial Drugs Cell Wall
Synthesis
  • Penicillins
  • Natural penicillins
  • Isolated from Penicillium mold
  • Narrow spectrum of activity
  • Susceptibility to penicillinases (or
    ßlactamases)
  • Semisynthetic penicillins
  • Chemically add new side chains to nucleus in
    attempt to
  • reduce susceptibility to penicillinase
  • extend their spectrum of activity

12
Targets of Antimicrobial Drugs Cell Wall
Synthesis
  • Penicillins
  • Semisynthetic penicillinase-resistant penicillins
  • Methicillin was the first
  • Resistant strains of staphylococci have become
    prevalent MRSA (methicillin-resistant
    Staphylococcus aureus)

13
Targets of Antimicrobial Drugs Protein Synthesis
  • Exploit 70S ribosomes of prokaryotic cells
  • Eukaryotic (host) cells 80S ribosomes
  • Host side effects due to mitochondrial toxicity
    (mitochondria 70S)

Figure 20.4
14
Targets of Antimicrobial Drugs Protein Synthesis
  • Tetracyclines
  • Broad spectrum of activity
  • Inhibit the association of tRNAs with the 70S
    ribosome
  • Prevent the addition of amino acids to the
    growing protein chain
  • Bacteriostatic

http//student.ccbcmd.edu/courses/bio141/lecguide/
unit2/control/images/tetres.gif
15
Other Targets of Antimicrobial Drugs
  • Plasma membranes
  • Drugs increase membrane permeability
  • Nucleic acid synthesis
  • May affect mammalian nucleic acid synthesis as
    well
  • Essential metabolite synthesis
  • Competitive inhibitors that prevent production of
    metabolites that are essential for
    growth/survival of the microbe

16
Testing effectiveness of antibiotics on
bacteria Disk-Diffusion Test
  • Zone of inhibition diameter reflects
    susceptibility of test organism to antibiotic drug

Figure 20.17
17
Effects of Combinations of Drugs
  • Antagonism the effect of two drugs together is
    less than the effect of either alone
  • Synergism the effect of two drugs together is
    greater than the effect of either alone
  • i.e. Polymyxin (membrane-disrupting drug) makes
    it easier for streptomycin to enter the cell

18
Effects of Combinations of Drugs
Figure 20.22
19
Antibiotic Resistance
  • Cellular mechanisms of antibiotic resistance
  • 1. Prevention of penetration of drug into cell
  • 2. Alteration of drug's target site (Mutation)
  • 3. Enzymatic destruction of drug
  • 4. Rapid ejection of the drug (Efflux)
  • Resistance genes are often on plasmids that can
    be transferred between bacteria
  • 1968 12,500 Guatemalans died of Shigella
    diarrhea
  • This strain contained a plasmid with resistance
    to four antibiotics

http//www.fda.gov/cvm/antiresistvideo.htm
20
Emergence of Antibiotic-resistant mutant bacteria
  • Antibiotic-resistant bacteria replacing the
    sensitive population
  • Every time an antibiotic is used, sensitive
    bacteria are killed, and resistant bacteria may
    survive and continue to grow (repopulate)
  • Presence of the antibiotic provides selective
    pressure
  • Selecting for antibiotic-resistant bacteria
  • Survival of the fittest

Figure 20.20
21
Infection
Antibiotic Administration
Inappropriate dose/duration
Appropriate dose/duration
Evolution of the surviving bacterial
population -SELECTIVE PRESSURE -Sensitive cells
die -Resistant cells survive, grow
Extinction of the whole bacterial
population -Sensitive cells die -Resistant cells
die
22
MRSA
  • About half of S. aureus infections in US are
    resistant to penicillin, methicillin,
    tetracycline, and erythromycin
  • Methicillin-resistant Staphylococcus aureus
  • Frequently used to describe S. aureus strains
    resistant to all penicillins
  • Quite common in hospitals
  • Current treatment for MRSA is vancomycin, the
    last weapon in the arsenal
  • VRSA was reported in 1997, and is (slowly) on the
    rise
  • As more antibiotics are discovered/synthesized,
    bacteria continue to adapt by developing and
    sharing antibiotic resistance

23
MRSA infections small red bumps ? deep, painful
abscesses
http//www.mayoclinic.com/images/image_popup/ans7_
staph_skin.jpg
24
Antibiotic Resistance
  • One of the worlds most pressing health problems
  • Misuse of antibiotics selects for resistant
    mutants Misuse includes
  • Using outdated, weakened antibiotics
  • Using someone else's leftover prescription
  • Failure to complete the prescribed regimen
  • Using antibiotics for the common cold and other
    inappropriate conditions
  • Use of antibiotics in animal feed

?Each of these applies selective pressure on a
microbial population, favoring resistant cells.
25
Acquisition of fluoroquinolone (FQ)-resistant
Campylobacter from poultry.
  • FQ approved for use in poultry in 1995
  • FQ use discontinued in 2001

www.cdc.gov/ncidod/EID/vol10no6/04-0403-G.htm
26
Strategies to Reduce Emergence of
Antibiotic-resistant bacteria
  • Prescription of antibiotics only when it will
    likely benefit the patient
  • Use an agent with narrow spectrum of activity
    when possible
  • Use antibiotics at the proper dose and duration

27
http//www.nearingzero.net/screen_res/nz149.jpg
28
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