Topical Antibiotics Med 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 1960s.

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

 Mupirocins 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

Daptomycin

Polymixin B

Member of the lipopeptide class of antibiotics, similar to daptomycin

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

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

A gramicidin channel

The gramicidins form small pores that cause leakage of essential cations from the cytoplasm

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 Grampositive 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.