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Topical%20Antibiotics

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Topical Antibiotics Like other aminoglycosides, neomycin works by binding to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis. – PowerPoint PPT presentation

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Title: Topical%20Antibiotics


1
Topical Antibiotics
2
  • Topical antibiotics help prevent infections
    caused by bacteria that get into minor cuts,
    scrapes, and burns.
  • Treating minor wounds with antibiotics allows
    quicker healing.
  • If the wounds are left untreated, the bacteria
    will multiply, causing pain, redness, swelling,
    itching, and oozing.
  • Untreated infections can eventually spread and
    become much more serious.

3
Which bacteria?
  • Most topical antibiotics are directed against
    Staphylococcus aureus and Streptococcus pyogenes.
  • The anaerobic Gram-positive bacterial species
    Propionibacterium acnes has been linked to acne.

4
Which topical antibiotics are common?
  • Some widely used topical antibiotics are
    bacitracin, neomycin, mupirocin, and polymyxin B.

5
  • Among the products that contain one or more of
    these ingredients are Bactroban (a prescription
    item), Neosporin, Polysporin, and Triple
    Antibiotic Ointment or Cream.

6
Classes of topical antibiotics
  • Cell wall synthesis inhibitors
  • Ribosome function inhibitors
  • Sulfa drugs
  • Burn treatment agents
  • Miscellaneous

7
Mupirocin (90 Pseudomonic acid A)
  • Isolated from Pseudomonas fluorescens
  • Antibacterial activity of substance from P.
    fluorescens noted in 1887
  • Purified in the 1960s.
  • Mupirocin works against Gram-positive bacteria
    only
  • Can be used to treat MRSA (although resistance is
    rising)

8
  • Ester linkage is rapidly hydrolyzed hepatically,
    thus precluding utility as an oral or intravenous
    antibiotic

9
  • Mupirocin inhibits bacterial isoleucyl-tRNA
    synthetase.

10
Products containing Mupirocin
11
Polymyxin B
12
Polymixin B
Daptomycin
Polymixin B
  • Member of the lipopeptide class of antibiotics,
    similar to daptomycin

13
Polymyxin Antibacterial activity
  • However, the polymyxins are only active against
    gram negative bacteria (P. aeruginosa, E. coli,
    K. pneumoniae), while daptomycin is used to treat
    gram positive bacteria
  • The polymyxins are highly nephrotoxic and are
    thus only used topically

14
Polymyxins Mechanism of action
  • Bind the the lipopolysaccharide in the outer
    membrane, thus destroying OM integrity.
  • Bind to the cytoplasmic membrane (to the
    phosphatidylethanolamine) and make the membrane
    more permeable.

15
Products containing polymyxin B
16
Bacitracin A
17
Bacitracin History
  • Isolated by John T. Goorley in 1943
  • Found in the infected compound fracture of the
    patient Margaret Tracy

18
Bacitracin Antibacterial Activity
  • Primarily used against gram positive bacteria S.
    aureus and Streptococci spp.
  • Most gram negative organisms are resistant

19
Bacitracin Mechanism
  • Bacitracin interferes with bacterial cell wall
    synthesis
  • Acts by blocking a step in the process whereby
    the key subunits are transferred from the
    cytoplasm

20
  • Specifically bacitracin tightly binds
    undecaprenyl pyrophosphate, preventing the
    hydrolysis into undecaprenyl phosphate
  • This step is essential for recycling of the
    carrier
  • Link

21
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22
Products containing Bacitracin
23
Gramicidin
Gramicidin S
24
Gramicidins
  • The Gramicidins are small peptides (15 amino
    acids)
  • Some, such as gramicidin S, are cyclic
  • Others, including Gramicidin A, B, C, and D, are
    linear
  • Commercial gramicidin is a mixture of compounds,
    with gramicidin A being major

25
Gramicidins
  • Gramicidin S is a powerful antibacterial agent,
    with broad range against a number of Gram
    positive and Gram negative microorganisms.

26
  • Unfortunately, Gramicidin S is hemolytic, and
    thus is limited to topical use.
  • Mechanism of action is believed to be at the
    cytoplasmic membrane.

27
Gramicidins Mechanism of action
A gramicidin channel
  • The gramicidins behave as ionophoric substances
  • The gramicidins self associate, thus forming
    small pores that cause leakage of essential
    cations from the cytoplasm

28
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29
  • Gramicidin is an unusual peptide, with
    alternating D L amino acids.
  • In lipid bilayer membranes, gramicidin dimerizes
    folds as a right-handed b-helix.
  • The dimer just spans the bilayer.
  • Primary structure of gramicidin (A)

HCO-L-Val-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-
L-Trp-D-Leu-L-Trp-D-Leu-L-Trp-D-Leu-L-Trp- NHCH2CH
2OH Note The amino acids are all
hydrophobic both peptide ends are modified
(blocked).
30
  • The outer surface of the gramicidin dimer, which
    interacts with the core of the lipid bilayer, is
    hydrophobic.
  • Ions pass through the more polar lumen of the
    helix.
  • Ion flow through individual gramicidin channels
    can be observed if a small number of gramicidin
    molecules is present in a lipid bilayer
    separating 2 compartments containing salt
    solutions.

31
Neomycin
32
Historical Aminoglycosides
  • Waksman and Schatz demonstrated the antibacterial
    activity of Streptomyces griseus in 1943
  • Streptomycin isolated in 1944
  • Neomycin isolated from Streptomyces fradiae in
    1949

33
Neomycin
  • Neomycin is extremely nephrotoxic, thus limiting
    its use to a topical antibiotic
  • Neomycin has excellent activity against gram
    negative bacteria and partial activity against
    gram positive strains
  • Some people have allergies to neomycin

34
  • Like other aminoglycosides, neomycin works by
    binding to the bacterial 30S ribosomal subunit,
    thus inhibiting protein synthesis.

35
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36
Silver sulfadiazine
37
  • Sulfa drug works by normal mechanism of
    interfering with the biosynthesis of folic acid
  • Heavy metals, like silver, seem to be toxic to
    bacteria, probably due to their ability to
    denature proteins through reaction with disulfide
    bonds

38
Uses
  • Used to treat burn patients

39
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40
Treatment of Acne Vulgaris
41
What Causes Acne?
  • Acne is a result of clogging of a hair follicle,
    and simultaneous activation of the sebaceous
    gland (thus producing more sebum).

42
  • A commensal bacterium, Propionibacterium acnes,
    which lives on the skin, but is also present in
    the follicle, causes inflammation and thus
    contributes to the problem.

43
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44
Propionibacterium acnes
  • Killing the bacteria can help with treatment of
    acne

45
Benzoyl Peroxide
  • Exact antibacterial mechanism is unknown, but
    presumably involves oxidation of essential
    bacterial structures.

46
Clindamycin
The antibiotic clindamycin is commonly used
topically in the treatment of acne
47
  • Recall that clindamycin is a member of the
    lincosamide class of antibacterial agents and
    acts at the bacterial ribosome.
  • Clindamycin is commonly used to treat aerobic
    Gram-positive bacteria.

48
Assigned Reading
  • Noah Scheinfeld A primer on topical antibiotics
    for the skin and eyes. Journal of drugs in
    dermatology JDD (2008), 7(4), 409-15.

49
Homework Question
  • List the primary target organism and the
    mechanism of action of the topical antibiotics
    discussed in this presentation.
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