These drugs commonly are used to treat superficial cutaneous infections (Table 65–8) (pyoderma) and non-infectious diseases, including acne rosacea, perioral dermatitis, hidradenitis suppurativa, auto-immune blistering diseases, sarcoidosis, and pyoderma gangrenosum (Carter, 2003). Topical agents are very effective for the treatment of superficial bacterial infections and acne vulgaris. Systemic antibiotics also are prescribed commonly for acne and deeper bacterial infections. The pharmacology of individual antibacterial agents is discussed in Section VI, Chemotherapy of Infectious Diseases. Only the topical and systemic antibacterial agents principally used in dermatology are discussed here.
Table 65-8Recommended Cutaneous Antifungal Therapy ||Download (.pdf) Table 65-8 Recommended Cutaneous Antifungal Therapy
|CONDITION ||TOPICAL THERAPY ||ORAL THERAPY |
|Tinea corporis, localized ||Azoles, allylamines ||— |
|Tinea corporis, widespread ||— ||Griseofulvin, terbinafine, itraconazole, fluconazole |
|Tinea pedis ||Azoles, allylamines ||Griseofulvin, terbinafine, itraconazole, fluconazole |
|Onychomycosis ||— ||Griseofulvin, terbinafine, itraconazole, fluconazole |
|Candidiasis, localized ||Azoles ||— |
|Candidiasis, widespread and mucocutaneous ||— ||Ketoconazole, itraconazole, fluconazole |
|Tinea versicolor, localized ||Azoles, allylamines || |
|Tinea versicolor, widespread ||— ||Ketoconazole, itraconazole, fluconazole |
Acne vulgaris is the most common dermatological disorder treated with either topical or systemic antibiotics. The anaerobe P. acnes is a component of normal skin flora that proliferates in the obstructed, lipid-rich lumen of the pilosebaceous unit, where O2 tension is low. P. acnes generates free fatty acids that are irritants and may lead to microcomedo formation and resulting inflammatory lesions. Suppression of cutaneous P. acnes with antibiotic therapy is correlated with clinical improvement (Tan, 2003).
Commonly used topical antimicrobials in acne include clindamycin (cleocin-t, others), erythromycin (eryderm, others), benzoyl peroxide, and antibiotic–benzoyl peroxide combinations (benzaclin, duac, others). Other antimicrobials used in treating acne include sulfacetamide (klaron, others), sulfacetamide/sulfur combinations (sulfacet-r, others), metronidazole (metrocream, metrogel, noritate), and azelaic acid (azelex, others). Systemic therapy is prescribed for patients with more extensive disease and acne that is resistant to topical therapy. In healthy individuals taking oral antibiotics for acne, laboratory monitoring is not necessary. Effective agents include tetracycline (sumycin, others), doxycycline (monodox, others), minocycline (minocin, others), and trimethoprim–sulfamethoxazole (bactrim, others). Antibiotics usually are administered twice daily, and doses are tapered after control is achieved.
The tetracyclines are the most commonly employed antibiotics because they are inexpensive, safe, and effective. The initial daily dose usually is 1 g in divided doses. Although tetracyclines are antimicrobial agents, efficacy in acne may be more dependent on anti-inflammatory activity. Minocycline has better GI absorption than tetracycline and may be less photosensitizing than either tetracycline or doxycycline. Side effects of minocycline include dizziness and hyperpigmentation of the skin and mucosa, serum sickness–like reactions, and drug-induced lupus erythematosus. With all the tetracyclines, vaginal candidiasis is a common complication that is readily treated with local administration of antifungal drugs.
Cutaneous Infections. Gram-positive organisms, including Staphylococcus aureus and Streptococcus pyogenes, are the most common cause of pyoderma. Skin infections with Gram-negative bacilli are rare, although they can occur in diabetics and patients who are immunosuppressed; appropriate parenteral antibiotic therapy is required for their treatment.
Topical therapy frequently is adequate for impetigo, the most superficial bacterial infection of the skin caused by S. aureus and S. pyogenes. Mupirocin (pseudomonic acid, bactroban, others), produced by Pseudomonas fluorescens, is effective for such localized infections. It inhibits protein synthesis by binding to bacterial isoleucyl-tRNA synthetase. Mupirocin is highly active against staphylococci and all streptococci except those of group D. It is less active against gram-negative organisms, but it has in vitro activity against Haemophilus influenzae, Neisseria gonorrhoeae, Pasteurella multocida, Moraxella catarrhalis, and Bordetella pertussis. Mupirocin is inactive against normal skin flora. Its antibacterial activity is enhanced by the acid pH of the skin surface. Mupirocin is available as a 2% ointment or cream and is applied three times daily. A nasal formulation is indicated to eradicate methicillin-resistant S. aureus (MRSA) nasal colonization.
Retapamulin ointment 1% (altabax) also is FDA approved for the topical treatment of impetigo caused by susceptible strains of S. aureus or S. pyogenes in patients ≥9 months of age. Retapamulin selectively inhibits bacterial protein synthesis by interacting at a site on the 50S subunit of bacterial ribosomes.
Topical therapy often is employed for prophylaxis of superficial infections caused by wounds and injuries. Neomycin is active against staphylococci and most gram-negative bacilli. It may cause allergic contact dermatitis, especially on disrupted skin. Bacitracin inhibits staphylococci, streptococci, and gram-positive bacilli. Polymyxin B is active against aerobic gram-negative bacilli. Neomycin, bacitracin, polymyxin B (neosporin original ointment, double antibiotic ointment, others) are sold alone or in various combinations with other ingredients (e.g., hydrocortisone, lidocaine, or pramoxine) in a number of over-the-counter (OTC) formulations for the first aid of minor scrapes, burns, and cuts.
Deeper bacterial infections of the skin include folliculitis, erysipelas, cellulitis, and necrotizing fasciitis. Because streptococcal and staphylococcal species also are the most common causes of deep cutaneous infections, penicillins (especially β lactamase–resistant β-lactams) and cephalosporins are the systemic antibiotics used most frequently in their treatment (Carter, 2003) (see Chapter 44). A growing concern is the increased incidence of skin and soft-tissue infections with hospital- and community-acquired MRSA and drug-resistant pneumococci. Infection with community-acquired MRSA often is susceptible to trimethoprim–sulfamethoxazole (Cohen and Grossman, 2004).
In addition to various traditional systemic antibiotics (such as erythromycin), novel antibacterial agents such as linezolid, quinupristin–dalfopristin, and daptomycin also have been approved for the treatment of complicated skin and skin-structure infections (see Chapter 53).
Fungal infections are among the most common causes of skin disease in the U.S., and numerous effective topical and oral antifungal agents have been developed. Griseofulvin, topical and oral imidazoles, triazoles, and allylamines are the most effective agents available. Examples include butenafine, clotrimazole, gentian violet, sertaconazole, ketoconazole, nystatin, oxiconazole, sulconazole, tolnaftate, undecylenic acid, and the antifungal combinations bensal hp, whitfield's ointment (benzoic acid + salicylic acid), versiclear lotion (25% sodium thiosulfate + 1% salicylic acid), castellani paint modified (basic fuchsin + phenol + resorcinol + acetone), and fungi-nail (1% resorcinol + 2% salicylic acid + 2% chloroxylenol + 0.5% benzocaine + 50% isopropyl alcohol). The pharmacology, uses, and toxicities of antifungal drugs are discussed in Chapter 57. This section will address the management of common cutaneous fungal diseases. Recommendations for cutaneous antifungal therapy are summarized in Table 65–8.
The azoles miconazole (micatin, others) and econazole (spectazole, others) and the allylamines naftifine (naftin) and terbinafine (lamisil, others) are effective topical agents for the treatment of localized tinea corporis and uncomplicated tinea pedis. Topical therapy with the azoles is preferred for localized cutaneous candidiasis and tinea versicolor.
Systemic therapy is necessary for the treatment of tinea capitis or follicular-based fungal infections. Oral griseofulvin has been the traditional medication for treatment of tinea capitis. Oral terbinafine is a safe and effective alternative to griseofulvin in treating tinea capitis in children (Moosavi et al., 2001).
Tinea Pedis. Topical therapy with the azoles and allylamines is effective for tinea pedis. Macerated toe web disease may require the addition of antibacterial therapy. Econazole nitrate, which has a limited antibacterial spectrum, can be useful in this situation. Systemic therapy with griseofulvin, terbinafine, or itraconazole (sporanox, others) is used for more extensive tinea pedis. It should be recognized that long-term topical therapy may be necessary in some patients after courses of systemic antifungal therapy.
Onychomycosis. Fungal infection of the nails most frequently is caused by dermatophytes and Candida. Mixed infections are common. Because up to one-third of dystrophic nails that appear clinically to be onychomycosis are actually due to psoriasis or other conditions, the nail must be cultured or clipped for histological examination before initiating therapy.
Systemic therapy is necessary for effective management of onychomycosis. Treatment of onychomycosis of toenails with griseofulvin for 12-18 months produces a cure rate of 50% and a relapse rate of 50% after 1 year. Terbinafine and itraconazole offer significant potential advantages. They quickly produce high drug levels in the nail, which persist after therapy is discontinued. Additional advantages include a broader spectrum of coverage with itraconazole and few drug interactions with terbinafine. Treatment of toenail onychomycosis requires 3 months with terbinafine (250 mg/day) or itraconazole (200 mg/day). Pulsed dosing with itraconazole for fingernail onychomycosis consists of 200 mg twice daily for 1 wk/mo for two pulses. Cure rates of ≥75% have been achieved with both drugs (Gupta et al., 1994a; Gupta et al., 1994b).
Ciclopirox topical (penlac, others) solution is a nail lacquer that is FDA-approved for the treatment of onychomycosis but demonstrates low complete cure rates (5.5-8.5%) after 1 year of daily application. Topical ciclopirox treatment of onychomycosis must include active removal of the unattached, infected nails as frequently as monthly.
Viral infections of the skin are very common and include verrucae (human papillomavirus [HPV]), herpes simplex virus (HSV), condyloma acuminatum (HPV), molluscum contagiosum (poxvirus), and chicken pox (varicella-zoster virus [VZV]). Acyclovir (zovirax), famciclovir (famvir, others), and valacyclovir (valtrex) frequently are used systemically to treat HSV and VZV infections (see Chapter 58). Cidofovir (vistide) may be useful in treating acyclovir-resistant HSV or VZV and other cutaneous viral infections (Anonymous, 2002a). Topically, acyclovir, docosanol (abreva), and penciclovir (denavir) are available for treating mucocutaneous HSV. Podophyllin (25% solution) and podofilox (condylox, others) 0.5% solution are used to treat condylomata. The immune response modifier imiquimod (aldara) is discussed in "Other Immunosuppressive and Anti-Inflammatory Agents." Interferons α-2b (intron a), α-n1 (not commercially available in the U.S.), and α-n3 (alferon n) may be useful for treating refractory or recurrent warts (Carter et al., 2004).
Agents Used to Treat Infestations
Infestations with ectoparasites such as lice and scabies are common throughout the world. These conditions have a significant impact on public health in the form of disabling pruritus, secondary infection, and in the case of the body louse, transmission of life-threatening illnesses such as typhus. Topical and oral medications are available to treat these infestations.
Permethrin is a synthetic pyrethroid that interferes with insect sodium transport proteins, causing neurotoxicity and paralysis. Resistance due to mutations in the transport protein has been reported in Cimex (bed bugs) and other insects.
The chemical is modeled after the natural insecticide found in the flower Chrysanthemum cinerariifolium. A 5% cream is available for the treatment of scabies, and a 1% cream, a cream rinse, and topical solutions are available OTC for the treatment of lice. Permethrin is approved for use in infants ≥2 months of age. Other agents used in the treatment of lice are pyrethrins + piperonyl butoxide (lotion, gel, shampoo, and mousse) and klout shampoo (acetic acid + isopropanol).
Lindane (γ-hexachlorocyclo-hexane) is an organochloride compound that induces neuronal hyperstimulation and eventual paralysis of parasites.
Lindane has been used as a commercial insecticide as well as a topical medication. Due to several cases of neurotoxicity in humans, the FDA has labeled lindane as a second-line drug in treating pediculosis and scabies and has highlighted the potential for neurotoxicity in children and adults weighing <110 pounds and in patients with underlying skin disorders such as atopic dermatitis and psoriasis (U.S. Food and Drug Administration, 2003). Lindane is contraindicated in premature infants and patients with seizure disorders. The FDA advises that lindane prescriptions should be limited to amounts for a single application.
Malathion (ovide) is an organophosphate that binds acetylcholinesterase in lice, causing paralysis and death. Its structure is:
It is approved for treatment of head lice in children ≥6 years of age. The currently available formulation contains alcohol and is flammable.
Benzyl alcohol (ulesfia) 5% lotion has recently received FDA approval for the treatment of lice. Benzyl alcohol inhibits lice from closing their respiratory spiracles, which allows the vehicle to obstruct the spiracles and causes the lice to asphyxiate. This mechanism may be less likely to cause resistance than traditional pesticides.
Ivermectin (stromectol) is an oral anthelmintic drug (see Chapter 51) approved to treat onchocerciasis and strongyloidiasis, but it also is effective in the off-label treatment of scabies and lice.
Because ivermectin does not cross the blood-brain barrier of humans, there is no major CNS toxicity. Nevertheless, minor CNS side effects include dizziness, somnolence, vertigo, and tremor. For both scabies and lice, ivermectin typically is given at a dose of 200 μg/kg, which may be repeated in 1 week. It should not be used in children weighing <15 kg.
Other, less effective topical treatments for scabies and lice include 10% crotamiton cream and lotion (eurax) and extemporaneously compounded 5% precipitated sulfur in petrolatum. The later preparation is sometimes used during pregnancy or during nursing (on infected mothers). Crotamiton and sulfur may be considered for use in patients in whom lindane or permethrin may be contraindicated.