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Topical Antibiotics
• Topical antibiotics help prevent infections caused by
bacteria that get into minor cuts, scrapes, and burns.
• Treating ...
Which bacteria?
• Most topical antibiotics are directed
against Staphylococcus aureus and
Streptococcus pyogenes.
• The an...
Which topical antibiotics are
common?
• Some widely used topical antibiotics are
bacitracin, neomycin, mupirocin, and
poly...
Classes of topical antibiotics
• Cell wall synthesis inhibitors
• Ribosome function inhibitors
• Sulfa drugs
• Burn treatm...
Mupirocin (90% Pseudomonic acid A)
• Isolated from Pseudomonas fluorescens
– Antibacterial activity of substance from P. f...
• Ester linkage is rapidly hydrolyzed
hepatically, thus precluding utility as an
oral or intravenous antibiotic
• Mupirocin inhibits bacterial isoleucyl-tRNA
synthetase.
Products containing Mupirocin
Polymyxin B
Polymixin B
• Member of the lipopeptide class of
antibiotics, similar to daptomycin
Daptomycin Polymixin B
Polymyxin: Antibacterial activity
• However, the polymyxins are only
active against gram negative bacteria
(P. aeruginosa,...
Polymyxins: Mechanism of action
• Bind the the lipopolysaccharide in the outer
membrane, thus destroying OM integrity.
• B...
Products containing polymyxin B
Bacitracin A
Bacitracin: History
• Isolated by John T. Goorley in 1943
• Found in the infected wound of the
patient Margaret Tracy
Bacitracin: Antibacterial
Activity
• Primarily used against gram positive
bacteria S. aureus and Streptococci
spp.
• Most ...
Bacitracin: Mechanism
• Bacitracin interferes with bacterial cell wall
synthesis
• Acts by blocking a step in the process
...
Products containing Bacitracin
Gramicidin
Gramicidin S
Gramicidins
• The Gramicidins are small
peptides (15 amino acids)
• Some, such as gramicidin S, are
cyclic
• Others, inclu...
Gramicidins
• Gramicidin S is a powerful antibacterial
agent, with broad range against a
number of Gram positive and Gram
...
Gramicidins: Mechanism of action
• The gramicidins behave as ionophoric
substances
• The gramicidins self associate, thus
...
Gramicidin is an unusual peptide,
with alternating D & L amino acids.
In lipid bilayer membranes,
gramicidin dimerizes & f...
The outer surface of the
gramicidin dimer, which
interacts with the core of the
lipid bilayer, is hydrophobic.
Ions pass t...
Neomycin
Historical: Aminoglycosides
• Waksman and Schatz demonstrated
the antibacterial activity of
Streptomyces griseus in 1943
•...
Neomycin
• Neomycin is extremely nephrotoxic,
thus limiting its use to a topical antibiotic
• Neomycin has excellent activ...
Mechanism of action
• Like other aminoglycosides, neomycin
works by binding to the bacterial 30S
ribosomal subunit, thus i...
Silver sulfadiazine
Mechanism of action
• Sulfa drug works by normal mechanism
of interfering with the biosynthesis of
folic acid
• Heavy meta...
Uses
• Used to treat burn patients
Treatment of Acne Vulgaris
What Causes Acne?
• Acne is a result of clogging of a hair follicle,
and simultaneous activation of the sebaceous
gland (t...
Propionibacterium acnes
• Killing the bacteria can help with treatment
of acne
Benzoyl Peroxide
• Exact antibacterial mechanism is unknown,
but presumably involves oxidation of
essential bacterial stru...
Clindamycin
The antibiotic clindamycin is commonly used topically in the
treatment of acne
Recall that clindamycin is a me...
Assigned Reading
• Noah Scheinfeld A primer on topical
antibiotics for the skin and eyes.
Journal of drugs in dermatology ...
Homework Question
• List the primary target organism and the
mechanism of action of the topical
antibiotics discussed in t...
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  1. 1. Topical Antibiotics
  2. 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. 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. 4. Which topical antibiotics are common? • Some widely used topical antibiotics are bacitracin, neomycin, mupirocin, and polymyxin B. • Among the products that contain one or more of these ingredients are Bactroban (a prescription item), Neosporin, Polysporin, and Triple Antibiotic Ointment or Cream.
  5. 5. Classes of topical antibiotics • Cell wall synthesis inhibitors • Ribosome function inhibitors • Sulfa drugs • Burn treatment agents • Miscellaneous
  6. 6. Mupirocin (90% Pseudomonic acid A) • Isolated from Pseudomonas fluorescens – Antibacterial activity of substance from P. fluorescens noted in 1887 – Purified in the 1960’s. • Mupirocin works against Gram-positive bacteria only • Can be used to treat MRSA (although resistance is rising)
  7. 7. • Ester linkage is rapidly hydrolyzed hepatically, thus precluding utility as an oral or intravenous antibiotic
  8. 8. • Mupirocin inhibits bacterial isoleucyl-tRNA synthetase.
  9. 9. Products containing Mupirocin
  10. 10. Polymyxin B
  11. 11. Polymixin B • Member of the lipopeptide class of antibiotics, similar to daptomycin Daptomycin Polymixin B
  12. 12. 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
  13. 13. 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.
  14. 14. Products containing polymyxin B
  15. 15. Bacitracin A
  16. 16. Bacitracin: History • Isolated by John T. Goorley in 1943 • Found in the infected wound of the patient Margaret Tracy
  17. 17. Bacitracin: Antibacterial Activity • Primarily used against gram positive bacteria S. aureus and Streptococci spp. • Most gram negative organisms are resistant
  18. 18. 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 • Specifically bacitracin tightly binds undecaprenyl pyrophosphate, preventing the hydrolysis into undecaprenyl phosphate • This step is essential for recycling of the carrier • Link
  19. 19. Products containing Bacitracin
  20. 20. Gramicidin Gramicidin S
  21. 21. 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
  22. 22. Gramicidins • Gramicidin S is a powerful antibacterial agent, with broad range against a number of Gram positive and Gram negative microorganisms. • Unfortunately, Gramicidin S is hemolytic, and thus is limited to topical use. • Mechanism of action is believed to be at the cytoplasmic membrane.
  23. 23. Gramicidins: Mechanism of action • The gramicidins behave as ionophoric substances • The gramicidins self associate, thus forming small pores that cause leakage of essential cations from the cytoplasm A gramicidin channel
  24. 24. Gramicidin is an unusual peptide, with alternating D & L amino acids. In lipid bilayer membranes, gramicidin dimerizes & folds as a right-handed β-helix. The dimer just spans the bilayer. Primary structure of gramicidin (A): Gramicidin dimer (PDB file 1MAG) 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- NHCH2CH2OH Note: The amino acids are all hydrophobic; both peptide ends are modified (blocked).
  25. 25. 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. Gramicidin dimer (PDB file 1MAG)
  26. 26. Neomycin
  27. 27. 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
  28. 28. 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
  29. 29. Mechanism of action • Like other aminoglycosides, neomycin works by binding to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis.
  30. 30. Silver sulfadiazine
  31. 31. Mechanism of action • 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
  32. 32. Uses • Used to treat burn patients
  33. 33. Treatment of Acne Vulgaris
  34. 34. What Causes Acne? • Acne is a result of clogging of a hair follicle, and simultaneous activation of the sebaceous gland (thus producing more sebum). • 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.
  35. 35. Propionibacterium acnes • Killing the bacteria can help with treatment of acne
  36. 36. Benzoyl Peroxide • Exact antibacterial mechanism is unknown, but presumably involves oxidation of essential bacterial structures.
  37. 37. Clindamycin The antibiotic clindamycin is commonly used topically in the treatment of acne 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.
  38. 38. 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.
  39. 39. Homework Question • List the primary target organism and the mechanism of action of the topical antibiotics discussed in this presentation.
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