Topical Antibiotics
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Transcript of Topical Antibiotics
Topical AntibioticsMed III lectures
Dr Keli
• 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.
Topical antibiotics
• Uses
• Preventing infections in clean wounds
• ↓Colonization of nares
• Mx of acne
• Deodorizer of the axilla
Which bacteria?
• Most topical antibiotics are directed against Staphylococcus aureus and B hemo Streptococcus pyogenes.
• The anaerobic Gram-positive bacterial species Propionibacterium acnes has been linked to acne.
Which topical antibiotics are common?
• Some widely used topical antibiotics are bacitracin, neomycin,Gentamycin mupirocin, and polymyxin B sulphate.
• Among the products that contain one or more of these ingredients are Bactroban (a prescription item), Neosporin, Polysporin, and Triple Antibiotic Ointment or Cream.
Classes of topical antibiotics
• Cell wall synthesis inhibitors
• Ribosome function inhibitors
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), impetigo caused by S Aureus and B heam strep
• Mupirocin’s 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, E. coli, K. pneumoniae, Enterobacter), while daptomycin is used to treat gram positive bacteria
• 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 Outer Membrane integrity.
• Bind to the cytoplasmic membrane (to the phosphatidylethanolamine) and make the membrane more permeable.
Products containing polymyxin B
Polymyxin B sulphate
• Resistant forms include
• Strains of serratia and proteus
• Gram positives
• Hypersensitivity is uncommon
Bacitracin A
Bacitracin: History
• Isolated by John T. Goorley in 1943
• Found in the infected compound fracture of the patient Margaret Tracy
Bacitracin: Antibacterial Activity
• Primarily used against gram positive bacteria S. aureus, pneumococci and Streptococci spp.
• Most anaerobic cocci are sensitive; neisseriae, tetenus and diptheria bacilli
• Most gram negative organisms are resistant
Bacitracin: Mechanism
• Bacitracin interferes with bacterial cell wall synthesis
Products containing Bacitracin
Bacitracin use
• May alone or in combination with Neomycin
• To decrease bacterial colonization of nares
• Prolonged use predisposes to dev of resistance
• May cause utricaria syndrome and allergic contact dermatitis
Gramicidin
Gramicidin S
Gramicidins
• The Gramicidins are small peptides (15 amino acids)
Gramicidins
• Gramicidin S is a powerful antibacterial agent, with broad range against a number of Gram positive and Gram negative microorganisms.
• Unfortunately, Gramicidin S causes hemolysis, and thus is limited to topical use.
• Mechanism of action is believed to be at the cytoplasmic membrane.
Gramicidins: Mechanism of action
• The gramicidins form small pores that cause leakage of essential cations from the cytoplasm
A gramicidin channel
Gramicicidin
• Available with other topical agents neomycin, polymyxin, bacitracin, nystatin
• Systemic toxicty limits its use
Historical: Aminoglycosides
• Waksman and Schatz demonstrated the antibacterial activity of Streptomyces griseus in 1943
• Neomycin isolated from Streptomyces fradiae in 1949
Neomycin
• Neomycin is extremely nephrotoxic, thus limiting its use to a topical antibiotic
• Neomycin has excellent activity against gram negative bacteria – E coli, proteus, Kleibsiella, Enterococci and partial activity against gram positive strains
• Some people have allergies to neomycin• Causes sensitization on eczematous skin• Cross sentization to other aminoglycosides is possible
• Like other aminoglycosides, neomycin works by binding to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis.
Silver sulfadiazine
• 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
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 (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.
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 structures.
Clindamycin
clindamycin is commonly used topically in the treatment of acne
• 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.
• The hydroalcoholic vehicle may cause drying and irritation• The water based gel and lotions are well tolarated
Erythromycin
• It inhibits P acnes
• Has a tendency of bacterial resistance
• May cause dryness may be combined with benzoyl peroxide
Metronidazole• Effective for acne rosea • MOA anti inflammatory to neutrophils• Inhibitory to Demodex brevis• Side effects dryness burning stinging
Sodium sulfacetamide• For Rx of acne, vulgaris and rosea• MOA inhibits utilization of p-aminobenzoic acid by
Propionibacterium acne• 4 % is absorbed percitaneously C/I in sulphonamide
hypersensitivity
Homework Question
• List the primary target organism and the mechanism of action of the topical antibiotics discussed in this presentation.