Title: Topical%20Antibiotics
1Topical 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.
3Which 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.
4Which 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.
6Classes of topical antibiotics
- Cell wall synthesis inhibitors
- Ribosome function inhibitors
- Sulfa drugs
- Burn treatment agents
- Miscellaneous
7Mupirocin (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.
10Products containing Mupirocin
11Polymyxin B
12Polymixin B
Daptomycin
Polymixin B
- Member of the lipopeptide class of antibiotics,
similar to daptomycin
13Polymyxin 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
14Polymyxins 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.
15Products containing polymyxin B
16Bacitracin A
17Bacitracin History
- Isolated by John T. Goorley in 1943
- Found in the infected compound fracture of the
patient Margaret Tracy
18Bacitracin Antibacterial Activity
- Primarily used against gram positive bacteria S.
aureus and Streptococci spp. - Most gram negative organisms are resistant
19Bacitracin 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
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22Products containing Bacitracin
23Gramicidin
Gramicidin S
24Gramicidins
- 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
25Gramicidins
- 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.
27Gramicidins 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
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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.
31Neomycin
32Historical Aminoglycosides
- Waksman and Schatz demonstrated the antibacterial
activity of Streptomyces griseus in 1943 - Streptomycin isolated in 1944
- Neomycin isolated from Streptomyces fradiae in
1949
33Neomycin
- 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.
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36Silver 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
38Uses
- Used to treat burn patients
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40Treatment of Acne Vulgaris
41What 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.
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44Propionibacterium acnes
- Killing the bacteria can help with treatment of
acne
45Benzoyl Peroxide
- Exact antibacterial mechanism is unknown, but
presumably involves oxidation of essential
bacterial structures.
46Clindamycin
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.
48Assigned Reading
- Noah Scheinfeld A primer on topical antibiotics
for the skin and eyes. Journal of drugs in
dermatology JDD (2008), 7(4), 409-15.
49Homework Question
- List the primary target organism and the
mechanism of action of the topical antibiotics
discussed in this presentation.