Antimicrobial Prophylaxis
in Dermatology
J.V. Hirschmann
Few circumstances in dermatology warrant antimi-
crobial prophylaxis. In cutaneous surgery postop-
erative infections are too infrequent and insuffi-
ciently severe to justify preventive antibiotics,
except rarely. Petrolatum is as effective as, and
cheaper than, topical antibiotic ointment to cover
surgical wounds. In patients with numerous staphy-
lococcal skin infections, oral clindamycin 150 mg
every day for 3 months safely reduces further
episodes. For recurrent cellulitis, oral penicillin or
erythromycin 250 mg twice daily or monthly intra-
muscular benzathine penicillin decreases subse-
quent attacks. In patients with frequent episodes
of genital or labial herpes simplex an antiviral
agent such as valacyclovir 500 mg to I g every
day is effective as a suppressant.
Copyright 9 2000 by W.B. Saunders Company
HE TERM "prophylaxis" has been applied to
T several different circumstances, depending
on whether the organism is exogenous or part of
the normal resident flora and whether the antimi-
crobial agent is given before or after the microbe
has reached the target tissues. Four different
situations existl:
Prevention of Infection by an Exogenous
Pathogen
The target organisms are not present on the
host and the antimicrobial agent, given before
exposure, destroys the pathogens when they ar-
rive. An example is penicillin to prevent strepto-
coccal pharyngeal infections in patients with
previous rheumatic fever.
Prevention of Infection of a Normally
Sterile Site by the Host's Resident Flora
The antimicrobial agent attains levels in the
host's tissues or body fluids that prevent infection
From Puget Sound VA Medical Center and University of
Washington School of Medicine, Seattle, WA.
Address reprint requests to J.V. Hirschmann, MD, Medical
Service (III), Puget Sound VA Medical Center, 1660 S Columbian
"~,hy,Seattle, WA 98108.
Copyright 9 2000 by W.B. Saunders Company
1085-5629/00/1901-0002510.00/0
doi:lO.lO53/sd.2000.7372
2 Seminars in Cutaneous Medicine and Surgew, Vo119, No I (March), 2000: pp 2-9
from the resident flora, typically present on a
nearby mucosal surface. Ahernativel); the anti-
infective agent eradicates the target organism
from the host's reservoir. An example is using
antibiotics to prevent postoperative wound infec-
tions following dermatologic surgery. The infect-
ing organisms are usually part of the resident flora
of the skin or nearby mucous membranes. An-
other is using topical mupirocin to eliminate
nasal carriage of Staphylococcus aureus in patients
with repeated staphylococcal skin infections.
Prevention of Disease by an Organism
That Already Infects the Host But Is
in a Dormant Stage
The initial infection occurred previously, and
the microbe remains alive, but inactive, in the
asymptomatic host. The antimicrobial agent can
either suppress or eradicate the organism. An
example is using isoniazid to prevent clinical
disease in an asymptomatic patient infected previ-
ously with Mycobacterium tuberculosis, which re-
mains in the body but is currently dormant.
Another is using an antiviral agent to avert
recurrent episodes of symptomatic mucocutane-
ous lesions in a patient infected with herpes
simplex.
Prevention of Disease by Pathogens That
Have Recently Infected the Host But Have
Not Yet Caused Clinical Manifestations
The organisms have already entered the host,
and the purpose of the antimicrobial agent is to
eradicate the microbes before they cause symptom-
atic disease. "Early therapy" is probably a more
accurate term than prophylaxis. An example is
giving an antimicrobial agent to someone who
has suffered a tick bite to prevent kyme borrelio-
sis.
Antimicrobial prophylaxis is most likely to
succeed when the duration of administration is
brief or the susceptibility of the organism stable.
Otherwise, because the agent used destroys sensi-
tive bacteria, the surviving organisms are likely to
ANTIMICROBIALPROPHYLAXISIN DERMATOLOGY
be resistant to it. Streptococcus pyogenes is an
example of a microbe with a stable susceptibility:
it remains sensitive to penicillin, and this agent,
even when given for years, continues to be
effective in preventing streptococcal infections.
Lengthy administration of antibiotics to patients
with indwelling urinary catheters, on the other
hand, does not decrease infections, because the
target organisms are a wide variety of species that
commonly become resistant to the medication
being used.
ANTIMICRGBIAL PROPHYLAXIS
TO PREVENT WOUND INFECTIONS
AFTER DERMATOLOGIC SURGERY
Antimicrobial administration to prevent postop-
erative wound infections is an example of brief
prophylaxis. These infections usually arise from
contamination by organisms present on the skin
or adjacent mucous membranes. The goal is to
use an antimicrobial agent that can kill most of
these bacteria when they enter the surgical wound
or reduce their numbers to a level that the local
host defenses can handle without an infection
occurring. Studies indicate that the anti-infective
agent must be present in the tissues at the time of
contamination or shortly afterwards to be effec-
tive. 2 Once the wound is closed, contamination
ordinarily ceases. Therefore, for most procedures,
a single preoperative dose of the antibiotic suf-
fices. 3 More preoperative doses are likely to
encourage the replacement of the resident flora
with resistant organisms, rendering the prophy-
laxis unsuccessful; postoperative doses are unnec-
essary because contamination has ended, they are
costly, and they are potentially hazardous in
increasing the risks of adverse effects.
For a procedure to justify the expense and
possible adverse effects of systemic antimicrobial
prophylaxis, however, postoperative infections
should be very frequent or particularly severe or
devastating, such as involvement of a prosthetic
heart valve or vascular graft. Surgical procedures
are typically stratified according to risk as4:
Clean
No inflammation is encountered and no entry
occurs into the respirator); alimentary, or genito-
urinary tracts. Without antimicrobial prophy-
laxis, the expected wound infection rate in these
procedures, which account for about 75% of all
surger); is less than 5% and typically about 1% to
2%.
Clean-Contaminated
The operation involves entry into the alimen-
tar); respiratory, or genitourinary tract but no
significant spillage occurs. The expected infection
rate in these procedures, which constitute about
15% of all surgeD', is approximately 10%. The rate
can be considerably higher in some operations,
such as colorectal surgeD', when the incision
crosses a mucosal surface that has a dense and
diverse resident flora and contamination with a
substantial number of organisms is common.
Contaminated
These operations involve acute nonpurulent
inflammation, gross spillage from the gastrointes-
tinal tract, a major break in sterile technique,
fresh trauma, or entry into infected biliary or
urinary tracts. The anticipated infection rate is
approximately 20%.
Dirty or Infected Wounds
These include traumatic wounds with retained
devitalized tissue, foreign bodies, fecal contamina-
tion, or already infected tissues. The expected
postoperative wound infection rate is approxi-
mately 30% to 40%.
The vast majority of dermatologic procedures
are dean surgery, and the rate and severity of
infections are too low to justify routine prophy-
laxis with systemic antimicrobials, although they
may reduce the incidence still further2 Some have
argued that patients undergoing laser resurfacing
of the facial skin to remove wrinkles should
receive prophylactic antibiotics but no compel-
ling information shows either a need or a benefit
in this setting. 6 A study intended to investigate
this question was too poorly designed and ex-
ecuted to provide any useful information. 7
With clean-contaminated dermatologic sur-
gery, such as resecting a deep basal cell carcinoma
of the nose, infections are uncon]mon and typi-
cally mild. Even with contaminated or dirty
dermatologic surgery, the risks and severity of
infection are low. Wound infections, for example,
are unusual after draining a cutaneous abscess,
and antimicrobials appear both unnecessary and
ineffective.8,9 Rarely, then, is systemic ar~timicro-
bial prophylaxis warranted to prevent postopera-
4 J.V. HIRSCHMANN
tive wound infections. In situations in which its
use seems justified, a single dose of an oral agent
administered approximately 1 hour before the
procedure will typically suffice. The antimicrobial
should be active against the usual pathogens,
primarily S aureus. Cephalexin, dicloxacillin, or
clindamycin would be reasonable choices.
An alternative approach is to apply systemic
antimicrobials topically. One method is to place
the powder of an agent ordinarily administered by
intravenous or intramuscular routes, such as
cefazolin, directly into the wound. 5 While the
dose may be smaller than is given parenterally,
absorption from the wound is substantial and the
systemic adverse effects are not avoided. 4 Another
tactic studied is to mix nafcillin with lidocaine to
achieve a concentration of 0.5 mg of the antibiotic
per milliliter of 1% buffered lidocaine with epi-
nephrine 1:100,000 and inject the combination
into the wound during preoperative local anesthe-
sia. 1~When compared in a double-blind, placebo-
controlled trial with lidocaine alone in 908 proce-
dures, predominantly Mohs' surgery, the infection
rate was reduced from 2.5% to 0.2%. The cost of
the antibiotic was less than 1 cent per patient, and
the antibiotic mixture retained its antibacterial
effects after 11 days of refrigeration, 60 days of
freezing, and 7 days at room temperature. How-
ever, it had lost its potency after 20 days at room
temperature. This approach is an effective, inex-
pensive measure t h a t is unnecessary for most
dermatologic surgery, because the baseline infec-
tion rate is so low already, but seems appropriate
for those procedures in which a wound infection
would leave a cosmetically significant defect.
The prophylactic use of antimicrobial oint-
ments formulated for topical use, such as bacitra-
cin or mupirocin, has been to cover the postopera-
tive wound. Since contamination of the wound
rarely occurs after the incision has been sutured,
this use is unlikely to decrease infection rates,
which depend on the organisms present in the
surgical site before closure. 1~ On the other hand,
in patients with open wounds, such as those after
a shave biopsy, infection is very uncommon and
unlikely to be lowered substantially by a topical
antibiotic. Although the prescription of such
agents is common, no evidence supports their
use. One double-blind, randomized study com-
pared the use o f bacitracin to white petrolatum as
the ointment used to cover the wounds in more
than 1,200 dermatologic procedures, including
shave and punch biopsies, electrodesiccation and
curettage, excision, Mohs' micrographic surgeD;
and dermabrasion. 12 The overall infection rate
was 1.5% and did not differ significantly between
the 2 groups. Allergic contact dermatitis devel-
oped in nearly 1% of those receiving bacitracin
but in none of those treated with petrolatum. The
infections that occurred in the bacitracin group
were caused by gram-negative bacilli, while those
in the petrolatum recipients were primarily from
S atu'eus. The costs of the bacitracin ointment and
the systemic antibiotics used to treat the wound
infections were nearly 4 times higher than those
for the petrolatum group.
ANTIBIOTICS TO PREVENT INFECTIVE
ENDOCARDITIS AND PROSTHETIC
INFECTIONS AFTER SURGERY
Although its efficacy remains unproved, antimi-
crobial prophylaxis has been widely endorsed and
used to prevent endocarditis and infections of
prostheses alter various procedures likely to cause
bacteremia. A study of 50 patients undergoing
dermatologic surgery showed no bacteremia in
those whose lesions had an intact skin surface
and 2.8% in eroded lesions, all of which grew
bacteria before excision. ~3 This level is too low to
justify routine preventive antibiotics, even in
patients with abnormal cardiac valves, and the
most recent guidelines of the American Heart
Association specifically recommend that prophy-
laxis not be given for "incision or biopsy of
surgically scrubbed skin. "14 Even with dental
procedures, which have much higher rates of
bacteremia than cutaneous surgery, endocarditis
rarely develops, and enthusiasm for prophylaxis
for them has markedly diminished) ~-17 Accord-
ingly, antibiotics before dermatologic surgery are
not routinely warranted in patients with valvular
heart disease. Even in incising and draining
clearly septic cutaneous loci, in which the inci-
dence of bacteremia is relatively high, 18the effects
of antibiotic therapy are uncertain and few, if any,
cases of endocarditis have unequivocally arisen in
these circumstances. A reasonable approach for
surgery on clearly infected tissues, analogous to
what one expert has suggested for dental proce-
dures, 16is to provide antibiotics for patients at the
highest risk: those with prosthetic valves or a
history of previous endocarditis. Because staphy-
ANTIMICROBIAL PROPHYLAXIS IN DERMATOLOGY
lococci and streptococci are the likely pathogens a
first-generation cephalosporin, an antistaphylo-
coccal penicillin, or clindamycin is appropriate.
The benefit of antimicrobial prophylaxis in
patients with indwelling prosthetic joints or vas-
cular grafts is also unproved. Most infections of
these arise from contamination at the time of their
insertion or from contiguous infection. 19,2~Few
are clearly of hematogenous origin and most of
these arise from distant sites of established suppu-
ration. Infection developing from transient bacter-
emia associated with medical or surgical proce-
dures, if it occurs at all, is very rare. Even with
certain kinds of dental work that have high rates
of bacteremia, antimicrobial prophylaxis is not
recommended) 9,21 In the experimental animal
studies of both vascular grafts and prosthetic
joints, the intensity and duration of bacteremia
necessary to cause an infection far exceed those
associated with bacteremias caused by cutaneous
procedures. 22-25 Accordingly, antimicrobial pro-
phylaxis before routine dermatologic surgery is
unnecessary in patients with orthopedic or vascu-
lar prostheses.
ANTIMICROBIAL PROPHYLAXIS
FOR RECURRENT STAPHYLOCOCCAL
SKIN INFECTIONS
S aureus is present in the anterior nares of
approximately 20% to 40% of the normal popula-
tion. 26 For most people, these organisms cause no
problems, but some patients are plagued by
recurrent staphylococcal skin infections, such as
furuncles. In these patients, nasal carriage of S
aureus represents a reservoir from which the
organism can reinfect the skin and most systemic
antibiotics, although successful in controlling the
cutaneous infection, achieve inadequate levels in
the nasal secretions to eradicate the staphylo-
cocci. One agent that does is oral clindamycin,
and a double-blind, controlled trial compared a
low dose (150 mg/d) of oral clindamycin versus a
placebo given for 3 months in 22 patients who
had 3 or more culture-proven staphylococcal skin
infections in the preceding 6 monthsY Among
the placebo recipients, staphylococcal infection
developed in 7 of 11 patients compared to 2 of t l
patients in the clindamycin group. Of the 9
patients free of infection after 3 months of clinda-
mycin, 6 had no further infections in the 9
months after discontinuing therapy, indicating a
5
long-term benefit. Although nasal cultures were
not performed, a likely mechanism for the favor-
able effect was an eradication of nasal carriage of
S aureus. The clindamycin was well-tolerated,
with no patients having diarrhea or other gastro-
intestinal complaints. Among outpatients treated
this way, the chance of having Clostridium difficile
colitis, a concern among hospitalized patients
receiving clindamycin, is very slight. This compli-
cation is almost exclusively a nosocomial infec-
tion, because this organism is present in the
bowel flora of less than 5% of outpatients and is
usually acquired in the hospital. 2s Furthermore,
the dose of clindamycin may be too small to alter
the colonic bacteri a enough to allow C difficile to
emerge as a dominant microbe.
An alternate approach in trying to prevent
recurrent staphylococcal skin infections is to use
intranasal topical antibiotics. Several topical
agents, such as gentamicin, mupirocin, bacitracin-
neomycin, bacitracin alone, and neomycin-
chlorhexidine, can eliminate the nasal carriage
rate in about 70% to 90% of patients compared to
0% to 27% disappearance either spontaneously or
with placebo. LLIn most of the studies, the staphy-
lococci returned shortly after the agent was discon-
tinued. Mupirocin appeared to be the most effec-
tive antibiotic and the one with the longest
duration of eradication. One trial examined the
utility of neomycin-bacitracin-polyrnixin B oint-
ment in 100 patients receiving oral isotretinoin,
an agent known to increase nasal carriage of S
aureus and skin infections caused by it. 29 After 5
months of treatment, nasal carriage increased
from 8% to 64% in the placebo group and from
10% to 18% in the topical antibiotic group. Three
months after isotretinoin therapy ended, the car-
riage rate was 52% in the placebo recipients
compared to 12% in those treated ~vith the
antibiotic. The clinical benefit was meager, how-
ever, although staphylococcal pyoderma occurred
in none of the antibiotic recipients, it developed
in only 2 patients in the control group (4%).
Another trial examined the use of mupirocin
ointment given twice a day for 5 days each month
for i year compared to placebo in 34 patients who
had developed 3 or more staphylococcal skin
infections in the previous year. 3~ Staphylococci
grew in 83 of the monthly nasal cultures in the 17
patients in the control group versus 22 in the
mupirocin recipients, and 52 episodes of staphy-
6 J.V. HIRSCHMANN
lococcal skin infections occurred in the former
compared to 26 in the latter. Both of these
differences were statistically significant. Mupiro-
cin ointment was well tolerated, and only one
patient developed mupirocin-resistant S aureus i n
the nasal cultures during the year of therapy.
In patients with recurrent staphylococcal skin
infections, therefore, both oral clindamycin and
topical mupirocin significantly decrease subse-
quent episodes. Although no trials have com-
pared these 2 approaches directly, oral clindamy-
cin appears more effective. Either tactic is
reasonable, but it is important to show in both
that the recurrent cutaneous problems are genu-
inely caused by S aureus by isolating this organ-
ism from cultures of the skin lesions. Many
clinicians assume that most cutaneous abscesses,
for example, are staphylococcal, but, in fact, the
majority have a mixture of aerobic and anaerobic
bacteria, with S aureus growing in only approxi-
mately 25%. 8,3t Even those with culture-proven
staphylococcal skin infections, however, should
not receive nasal mupirocin unless cultures show
that S aureus is also present in the anterior nares.
ANTIBIOTICS TO PREVENT RECURRENT
CELLULITIS (ERYSIPELAS) AND IMPETIGO
Some patients develop recurrent cellulitis (of-
ten called erysipelas, especially in the European
literature), particularly of the legs. Predisposing
factors include venous insufficiency, lymph-
edema, previous trauma, edema from several
causes such as congestive heart failure or liver
disease, prior episodes of cellulitis, and saphe-
nous venectomy for coronary artery bypass sur-
get): 32-3+ Cultures of skin aspirates, blood, and
cutaneous biopsies are usually negative, with
streptococci being, by far, the most frequent
organism isolated. Direct immunofluorescent an-
tigen detection in skin biopsies, combined with
the data from cultures, implicates streptococci of
various groups including A, B, C, and G in
virtually all cases. 35 A site of entry for these
organisms is often inapparent and they ordinarily
do not colonize intact skin. In many circum-
stances, especially with patients who have had a
previous venectom); the spaces between the toes
of the ipsilateral foot shows cracking, maceration,
scaling, or fissuring, usually from dermatophyte
infection. In one study of 24 episodes of cellulitis
such abnormalities were present in 83% of the
episodes. 36 Hemolytic streptococci grew from 85%
of cultures of the interdigital toe spaces of these
patients compared to 0% in a control group with
the interdigital changes but no history of celluli-
tis. Apparently, this abnormal skin environment
allows these bacteria to grow, and the toe webs,
therefore, represent a reservoir from which these
organisms can directly invade or can spread to
adjacent skin where they can enter through areas
of minor trauma or impaired local defenses.
Treating tinea pedis in patients with recurrent leg
cellulitis typically prevents further episodes. 32,34
If the toe spaces are normal, another area to
culture is the distal anal canal, which grew Group
G streptococci from 4 patients with recurrent leg
cellulitis. 37
In those without a clear reservoir for strepto-
cocci or in whom cellulitis continues to occur
despite treatment of the apparent source, prophy-
laxis with systemic antimicrobials may be helpful.
One study, performed in the early 1960s, gave
benzathine penicillin once a month or oral peni-
cillin or erythromycin daily for I to 2 weeks each
month to 21 patients with lymphedema and
numerous episodes of recurrent cellulitis in the
preceding months. 38 During a follow-up period of
about 30 months, 18 patients were completely
free of attacks and 3 had only minor episodes. In
another study, 32 patients who had 2 or more
episodes of cellulitis in the preceding year ran-
domly received erythromycin 250 mg twice daily
for 18 months or no therapy.39 None of the
patients given erythromycin developed infec-
tions, compared to 8 of 16 in the control group. A
third trial involved monthly injections of 1.2
million U of benzathine penicillin G in patients
who had an episode of streptococcal leg celluli-
tis.4~ Patients who declined prophylaxis were the
controls. Recurrence developed in 4 of 31 (12.9%)
of those receiving penicillin versus 16 of 84
(19%) of the patients who refused it. The differ-
ence is not statistically significant. Because the
criterion for entry was a single episode of celluli-
tis rather than a history of recurrences, the
number of participants may have been too small
to demonstrate a benefit for the subgroup of
patients likely to have multiple episodes. For
patients with recurrent attacks of leg cellulitis in
which a reservoir is not found or in whom
treatment of that reservoir does not terminate the
ANTIMICROBIALPROPHYLAXISIN DERMATOLOGY
recurrences, daily oral penicillin or erythromycin,
both in doses of 250 mg twice dail); is a good
prophylactic measure. In those with poor compli-
ance for that regimen, monthly intramuscular
benzathine penicillin 1.2 to 4.8 million U repre-
sents a reasonable alternative.
One trial examined the effect of an antibiotic
ointment containing bacitracin, polymixin, and
neomycin compared to a placebo ointment in
preventing impetigo in children 2 to 5 years old in
Alabama from July to early October, the peak
season for streptococcal pyoderma. 41 The oint-
ment was applied thrice daily to insect bites and
other breaks i n t h e skin. Streptococcal skin infec-
tions developed in 15 of 32 (47%) patients
receiving the placebo versus 4 of 27 (15%) of the
antibiotic group, a statistically significant differ-
ence.
ANTIMICROBIAL PROPHYLAXIS TO PREVENT
LYME BORRELIOSlS AFTER TICK BITES
The probability of contracting symptomatic
infection with Borrelia burgdorferi after a tick bite
in an endemic area is about 0.027 but with a range
of 0.012 to 0.05. 42 Two studies have examined the
benefit of prescribing antibiotics after tick bites to
prevent this disease. In a trial conducted in an
endemic location in Connecticut, 387 children
and adults bitten by a deer tick within the
previous 72 hours were randomized to receive
250 mg of amoxicillin or placebo 3 times a day for
10 days. 43 Of the 344 deer ticks submitted and
analyzed for B bmgdorfeli, 15% were infected. The
risk of Lyme disease was 1.2% in the placebo
group versus 0% in the antibiotic recipients, an
insignificant difference. In a similar study con-
ducted in Westchester County, NY, another en-
demic area, children bitten within 72 hours by a
deer tick received either a placebo or an antibi-
otic: either penicillin or tetracycline 250 mg 4
times daily for 10 days. 44 Erythema migrans
developed in one of the placebo recipients. Both
trials concluded that the risk of Lyme disease was
too low in endemic areas to justify prophylaxis in
patients who suffered tick bites.
ANTIMICROBIAL PROPHYLAXIS FOR
RECURRENT HERPES SIMPLEX INFECTIONS
Herpes simplex virus (HSV) infection is com-
mon in adults in the United States, who have a
seropositivity of about 50% to 60% for HSV-1,
7
which primarily affects the oral mucosa, and 20%
for HSV-2, 4~ which usually involves the genital
mucosa. Whether the primary infection causes
clinical disease or is asymptomatic, which is
common, 46 the virus enters the sensory nerves at
the primary site and travels retrograde to the
sensory neurons, where it remains for the dura-
tion of the host's lifespan. Periodicall); the infec-
tion becomes active, and painful vesicular lesions
develop near the initial site of inoculation. Recur-
rent episodes are common, especially with genital
involvement, in which the average duration of
pain is about 6 days in women, 4 days in men.
The lesions heal in approximately 9 to 10 days.
Recurrences tend to be shorter and less severe
with oral lesions, which are often precipitated by
certain factors,such as trauma, ultraviolet light,
menstruation, fever, and emotionalstress. The
pain, typically mild, usually lasts less than 4 days,
and the lesions commonly disappear within 7
days.
When recurrences are common (6 or more
episodes per year) or particularly severe, espe-
cially with genital lesions, oral antiviral agents, if
taken on a daily basis, can diminish the frequency
of episodes. Acyclovir 400 mg twice dail); famci-
clovir 250 mg twice dail); or valacyclovir--either
500 mg or 1 g every day--are all significantly
better than placebo in preventing relapses of
genital HSV infection. 47 Comparisons between
these regimens are few4s but they seem approxi-
mately equivalent, and the least expensive ap-
proach is one of 2 valacyclovir doses, 47 the larger
of which seems better for patients with more than
10 attacks annually. 48 These programs will render
50% to 75% of patients free of recurrences during
a year of medication ingestion, 47 and in those who
do have breakthrough attacks, the frequency of
relapses is usually substantially less. Over time,
many patients have a diminishing number of
episodes, even if they do not receive prophylaxis;
accordingl); it is worthwhile to discontinue the
medication periodically (perhaps once a year) to
determine if the incidence of recurrences has
decreased sufficiently to render further prophy-
laxis unnecessary. 49
Such long-term suppression is less commonly
used in oral herpes because the attacks are
shorter, milder, and less frequent. With i~articu-
larly numerous, severe, or protracted episodes
8 J.V. HIRSCHMANN
a c y c l o v i r 400 m g t w i c e daily will r e d u c e the
i n c i d e n c e by a p p r o x i m a t e l y 50%. 50 A n a l t e r n a t i v e
a p p r o a c h in p a t i e n t s w i t h s u n - i n d u c e d attacks
has b e e n to initiate a c y c l o v i r 400 to 800 m g t w i c e
daily 12 h o u r s b e f o r e e x p o s u r e . T h e results of 2
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