ANTIBACTERIAL AGENTS
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
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 (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 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 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 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.
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 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).
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.
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.
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.
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.
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