Antibacterial Agents

ANTIBACTERIAL AGENTS

TOPICAL ANTIBACTERIAL PREPARATIONS

Topical antibacterial agents may be useful in preventing infections in clean wounds, in the early treatment of infected dermatoses and wounds, in reducing colonization of the nares by staphylococci, in axillary deodorization, and in the management of acne vulgaris. The efficacy of antibiotics in these topical applications is not uni-form.

Some topical anti-infectives contain corticosteroids in addition to antibiotics. There is no convincing evidence that topical corti-costeroids inhibit the antibacterial effect of antibiotics when the two are incorporated in the same preparation. In the treatment of secondarily infected dermatoses, which are usually colonized with streptococci, staphylococci, or both, combination therapy may prove superior to corticosteroid therapy alone. Antibiotic-corticosteroid combinations may be useful in treating diaper der-matitis, otitis externa, and impetiginized eczema.

The selection of a particular antibiotic depends upon the diag-nosis and, when appropriate, in vitro culture and sensitivity stud-ies of clinical samples. The pathogens isolated from most infected dermatoses are group A β-hemolytic streptococci, Staphylococcusaureus, or both. The pathogens present in surgical wounds will bethose resident in the environment. Information about regional patterns of drug resistance is therefore important in selecting a therapeutic agent. Prepackaged topical antibacterial preparations that contain multiple antibiotics are available in fixed dosages well above the therapeutic threshold. These formulations offer the advantages of efficacy in mixed infections, broader coverage for infections due to undetermined pathogens, and delayed microbial resistance to any single component antibiotic.

BACITRACIN & GRAMICIDIN

Bacitracin and gramicidin are peptide antibiotics, active against gram-positive organisms such as streptococci, pneumococci, and staphylococci. In addition, most anaerobic cocci, neisseriae, teta-nus bacilli, and diphtheria bacilli are sensitive. Bacitracin is com-pounded in an ointment base alone or in combination with neomycin, polymyxin B, or both. The use of bacitracin in the anterior nares may temporarily decrease colonization by patho-genic staphylococci. Microbial resistance may develop following prolonged use. Bacitracin-induced contact urticaria syndrome, including anaphylaxis, occurs rarely. Allergic contact dermatitis occurs frequently, and immunologic allergic contact urticaria rarely. Bacitracin is poorly absorbed through the skin, so systemic toxicity is rare.

Gramicidin is available only for topical use, in combination with other antibiotics such as neomycin, polymyxin, bacitracin, and nystatin. Systemic toxicity limits this drug to topical use. The incidence of sensitization following topical application is exceed-ingly low in therapeutic concentrations.

MUPIROCIN

Mupirocin (pseudomonic acid A) is structurally unrelated to other currently available topical antibacterial agents. Most gram-positive aerobic bacteria, including methicillin-resistant S aureus (MRSA), are sensitive to mupirocin . It is effective in the treatment of impetigo caused by S aureus and group A β-hemolytic streptococci.

Intranasal mupirocin ointment for eliminating nasal carriage of S aureus may be associated with irritation of mucous membranescaused by the polyethylene glycol vehicle. Mupirocin is not appre-ciably absorbed systemically after topical application to intact skin.

RETAPAMULIN

Retapamulin is a semisynthetic pleromutilin derivative effective in the treatment of uncomplicated superficial skin infection caused by group A β-hemolytic streptococci and S aureus, excluding MRSA. Topical retapamulin 1% ointment is indicated for use in adult and pediatric patients, 9 months or older, for the treatment of impetigo. Recommended treatment regimen is twice-daily application for 5 days. Retapamulin is well tolerated with only occasional local irritation of the treatment site. To date only four cases of allergic contact dermatitis have been reported.

POLYMYXIN B SULFATE

Polymyxin B is a peptide antibiotic effective against gram-negative organisms, including Pseudomonas aeruginosa, Escherichia coli, enterobacter, and klebsiella. Most strains of proteus and serratia are resistant, as are all gram-positive organisms. Topical prepara-tions may be compounded in either a solution or ointment base.

Numerous prepackaged antibiotic combinations containing poly-myxin B are available. Detectable serum concentrations are diffi-cult to achieve from topical application, but the total daily dose applied to denuded skin or open wounds should not exceed 200 mg in order to reduce the likelihood of neurotoxicity and nephrotoxicity. Allergic contact dermatitis to topically applied polymyxin B sulfate is uncommon.

NEOMYCIN & GENTAMICIN

Neomycin and gentamicin are aminoglycoside antibiotics active against gram-negative organisms, including E coli, proteus, kleb-siella, and enterobacter. Gentamicin generally shows greater activ-ity against P aeruginosa than neomycin. Gentamicin is also more active against staphylococci and group A β-hemolytic strepto-cocci. Widespread topical use of gentamicin, especially in a hospi-tal environment, should be avoided to slow the appearance of gentamicin-resistant organisms.

Neomycin is available in numerous topical formulations, both alone and in combination with polymyxin, bacitracin, and other antibiotics. It is also available as a sterile powder for topical use. Gentamicin is available as an ointment or cream.

Topical application of neomycin rarely results in detectable serum concentrations. However, in the case of gentamicin, serum concentrations of 1–18 mcg/mL are possible if the drug is applied in a water-miscible preparation to large areas of denuded skin, as in burned patients. Both drugs are water-soluble and are excreted primarily in the urine. Renal failure may permit the accumulation of these antibiotics, with possible nephrotoxicity, neurotoxicity, and ototoxicity.

Neomycin frequently causes allergic contact dermatitis, par-ticularly if applied to eczematous dermatoses or if compounded in an ointment vehicle. When sensitization occurs, cross-sensitivity to streptomycin, kanamycin, paromomycin, and gentamicin is possible.

TOPICAL ANTIBIOTICS IN ACNE

Several systemic antibiotics that have traditionally been used in the treatment of acne vulgaris have been shown to be effective when applied topically. Currently, four antibiotics are so utilized: clindamycin phosphate, erythromycin base, metronidazole, and sulfacetamide. The effectiveness of topical therapy is less than that achieved by systemic administration of the same antibiotic. Therefore, topical therapy is generally suitable only in mild to moderate cases of inflammatory acne.

Clindamycin

Clindamycin has in vitro activity against Propionibacterium acnes; this has been postulated as the mechanism of its beneficial effect in acne therapy. Approximately 10% of an applied dose is absorbed, and rare cases of bloody diarrhea and pseudomembra-nous colitis have been reported following topical application. The hydroalcoholic vehicle and foam formulation (Evoclin) may causedrying and irritation of the skin, with complaints of burning and stinging. The water-based gel and lotion formulations are well tolerated and less likely to cause irritation. Allergic contact der-matitis is uncommon. Clindamycin is also available in fixed-combination topical gels with benzoyl peroxide (Acanya, BenzaClin, Duac), and with tretinoin (Ziana).

Erythromycin

In topical preparations, erythromycin base rather than a salt is used to facilitate penetration. The mechanism of action of topical erythromycin in inflammatory acne vulgaris is unknown but is presumed to be due to its inhibitory effects on P acnes. One of the possible complications of topical therapy is the development of antibiotic-resistant strains of organisms, including staphylococci. If this occurs in association with a clinical infection, topical eryth-romycin should be discontinued and appropriate systemic antibi-otic therapy started. Adverse local reactions to erythromycin solution may include a burning sensation at the time of applica-tion and drying and irritation of the skin. The topical water-based gel is less drying and may be better tolerated. Allergic contact dermatitis is uncommon. Erythromycin is also available in a fixed combination preparation with benzoyl peroxide (Benzamycin) for topical treatment of acne vulgaris.

Metronidazole

Topical metronidazole is effective in the treatment of rosacea. The mechanism of action is unknown, but it may relate to the inhibi-tory effects of metronidazole on Demodex brevis; alternatively, the drug may act as an anti-inflammatory agent by direct effect on neutrophil cellular function. Oral metronidazole has been shown to be a carcinogen in susceptible rodent species, and topical use during pregnancy and by nursing mothers and children is there-fore not recommended.

Adverse local effects of the water-based gel formulation (MetroGel) include dryness, burning, and stinging. Less drying formulations may be better tolerated (MetroCream, MetroLotion, and Noritate cream). Caution should be exercised when applying metronidazole near the eyes to avoid excessive tearing.

Sodium Sulfacetamide

Topical sulfacetamide is available alone as a 10% lotion (Klaron) and as a 10% wash (Ovace), and in several preparations in combi-nation with sulfur for the treatment of acne vulgaris and acne rosacea. The mechanism of action is thought to be inhibition of Pacnes by competitive inhibition of p-aminobenzoic acid utiliza-tion. Approximately 4% of topically applied sulfacetamide is absorbed percutaneously, and its use is therefore contraindicated in patients having a known hypersensitivity to sulfonamides.

Dapsone

Topical dapsone is available as a 5% gel (Aczone) for the treatment of acne vulgaris. The mechanism of action is unknown. Topical use in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency has not been shown to cause clinically relevant hemoly-sis or anemia. However, a slight decrease in hemoglobin concen-tration was noted in patients with G6PD deficiency, suggestive of mild hemolysis. Adverse local side effects include mild dryness, redness, oiliness, and skin peeling. Application of dap-sone gel followed by benzoyl peroxide may result in a temporary yellow discoloration of the skin and hair.