• Topical antibiotics help prevent infections caused by
bacteria that get into minor cuts, scrapes, and burns.
• Treating minor wounds with antibiotics allows quicker
• If the wounds are left untreated, the bacteria will
multiply, causing pain, redness, swelling, itching, and
• Untreated infections can eventually spread and
become much more serious.
• Most topical antibiotics are directed
against Staphylococcus aureus and
• The anaerobic Gram-positive bacterial
species Propionibacterium acnes has
been linked to acne.
Which topical antibiotics are
• Some widely used topical antibiotics are
bacitracin, neomycin, mupirocin, and
• Among the products that contain one or
more of these ingredients are
Bactroban (a prescription item),
Neosporin, Polysporin, and Triple
Antibiotic Ointment or Cream.
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
• Can be used to treat MRSA (although resistance is
• Ester linkage is rapidly hydrolyzed
hepatically, thus precluding utility as an
oral or intravenous antibiotic
• 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, E. coli, K. pneumoniae),
while daptomycin is used to treat gram
• The polymyxins are highly nephrotoxic
and are thus only used topically
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.
• Isolated by John T. Goorley in 1943
• Found in the infected wound of the
patient Margaret Tracy
• Primarily used against gram positive
bacteria S. aureus and Streptococci
• Most gram negative organisms are
• Bacitracin interferes with bacterial cell wall
• 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
• The Gramicidins are small
peptides (15 amino acids)
• Some, such as gramicidin S, are
• Others, including Gramicidin A,
B, C, and D, are linear
• Commercial gramicidin is a
mixture of compounds, with
gramicidin A being major
• Gramicidin S is a powerful antibacterial
agent, with broad range against a
number of Gram positive and Gram
• Unfortunately, Gramicidin S is
hemolytic, and thus is limited to topical
• Mechanism of action is believed to be
at the cytoplasmic membrane.
Gramicidins: Mechanism of action
• The gramicidins behave as ionophoric
• The gramicidins self associate, thus
forming small pores that cause leakage
of essential cations from the cytoplasm
A gramicidin channel
Gramicidin is an unusual peptide,
with alternating D & L amino acids.
In lipid bilayer membranes,
gramicidin dimerizes & folds as a
The dimer just spans the bilayer.
Primary structure of gramicidin
(PDB file 1MAG)
NHCH2CH2OH Note: The amino acids are all
hydrophobic; both peptide ends are modified (blocked).
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.
(PDB file 1MAG)
• Waksman and Schatz demonstrated
the antibacterial activity of
Streptomyces griseus in 1943
• Streptomycin isolated in 1944
• Neomycin isolated from Streptomyces
fradiae in 1949
• 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
Mechanism of action
• Like other aminoglycosides, neomycin
works by binding to the bacterial 30S
ribosomal subunit, thus inhibiting
Mechanism of action
• Sulfa drug works by normal mechanism
of interfering with the biosynthesis of
• Heavy metals, like silver, seem to be
toxic to bacteria, probably due to their
ability to denature proteins through
reaction with disulfide bonds
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.
• Killing the bacteria can help with treatment
• Exact antibacterial mechanism is unknown,
but presumably involves oxidation of
essential bacterial structures.
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
Clindamycin is commonly used to treat aerobic Gram-
• Noah Scheinfeld A primer on topical
antibiotics for the skin and eyes.
Journal of drugs in dermatology : JDD
(2008), 7(4), 409-15.
• List the primary target organism and the
mechanism of action of the topical
antibiotics discussed in this
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