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.