DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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 lactamase–resistant -
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).
Antifungal Agents
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, WHIT-
FIELD’S OINTMENT (benzoic acid + salicylic acid), VER-
SICLEAR 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
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CHAPTER 65
DERMATOLOGICAL PHARMACOLOGY