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December 1988, Vol. 27, No.

10

Pharmacology and Therapeutics

Treatment of Impetigo and Ecthyma


A Comparison of Sulconazole with Miconazole

SIEGFRIED NOLTING, M.D., AND WOLFGANG B. STRAUSS, B.S.

From the Abteilung fur Dermatomikrobiologie, Westf. purpose of this study was to compare the antibacterial
Wilhelms University, Munster, West Cermany, and Syntex efficacy and safety of sulconazole nitrate 1 % cream
Research, International Clinical Studies, Palo Alto, California
with miconazole nitrate 2% cream, another imidazole
derivative that has been reported as effective against
S. aureus and streptococci," in the 2-week treatment
ABSTRACT: In a randomized, double-blind, parallel compar- of patients with impetigo and ecthyma lesions caused
ative study of 80 patients, impetigo and ecthyma were treated by group A /3-hemolytic streptococci or pathogenic
effectively by sulconazole nitrate 1% cream and miconazole staphylococci or both. Informed consent for participa-
nitrate 2% cream applied to lesions twice daily for 14 days.
tion in this study was provided by or for all the pa-
When treatment began, bacterial cultures from all pyodermal
tients, and the study was conducted in accordance
lesions yielded Croup A ^-hemolytic streptococci or patho-
with the Declaration of Helsinki.
genic staphylocoed. Among the 32 sulconazole-treated im-
petigo patients, bacterial cultures from 26 (69%) were nega-
tive by treatment day 4, and those from all 32 (100%) were Materials and Methods
negative by treatment day 7; among the 34 miconazole-
Patients
treated impetigo patients, cultures from 17 (50%) were nega-
tive by treatment day 4, cultures from 32 (94.1%) were nega- Male and female patients of any age with a clinical diag-
tive by treatment day 7, and cultures from 29 (97%) were nosis of either Impetigo or ecthyma and with bacterial cul-
negative by treatment day 14. Each treatment promptly re- tures positive for Group A (3-hemolytic streptococci or coag-
lieved the pyodermal signs (crusts, vesicles, pustules, bullae, ulase-positive S. aureus or both were admitted to the trial.
Patients with chronic pyodermas (individual lesions present
and exudate). Both agents were considered to be safe and
for longer than 4 weeks) or who required the continuing use
effective medications for treating impetigo and ecthyma. of topical or systemic antibiotics first applied within 2 days
or 1 week of enrollment, respectively, were excluded from

S everal years ago, Schachner et al.^ reported that up


to 98% of the Staphylococcus aureus cultured
from pyodermal lesions of children were resistant to
the trial.

Methods
penicillin and other antibiotics. This finding precipi-
tated a search for other agents that would be effective The study used a randomized, double-blind, parallel
group design. When patients enrolled in the trial, they were
against the organisms causing pyoderma in children
allocated, according to a computer-generated randomiza-
and adults. tion code, to receive either sulconazole nitrate 1 % cream or
Sulconazole nitrate, an imidazole derivative, is an miconazole nitrate 2 % cream.
active antifungal agent when used topically.^"'' It also The patients were instructed to wash all lesions gently
exhibits in vitro activity against gram-positive bacteria with nonmedicated soap (removing any crusts), rinse them,
blot them dry, and then apply the medication carefully,
(Staphylococcus aureus. Streptococcus faecatis, Cory-
completely covering the skin area under treatment. This
nebacterium acnes, and Erysipetothrix insidiosa) and procedure was to be followed twice dailyin the morning
against the pathogenic organisms associated with der- and at bedtimefor 14 days. The same physician examined
matophytosis, tinea versicolor, and candidiasis''; how- and evaluated each patient when therapy was initiated and
ever, there is no known published report of its activity on treatment days 4, 7, and 14. No other medication, either
against cutaneous bacterial infections in humans. The topical or systemic, was permitted during the trial.
One representative lesion was selected for each patient at
the initial visit. At every visit, material from this lesion was
Address for correspondence: Prof. Siegfried Nolting, Hautklinik removed and sent to a laboratory for bacterial culture cin
der Westfalischen Wilhelms-Universitat, Abteilung fur Dermato- media selective for 5. aureus and Group A /3-hemolytic
mikrobiologie, 4400 Munster, West Cermany. streptococci. All lesions were examined, and the severity of

716
No. 10 SULCONAZOLE VS. MICONAZOLE IN IMPETIGO AND ECTHYMA Nolting and Strauss

TABLE 1. Demographic Data and Bacterial Culture Results 66 patients with a diagnosis of impetigo, 32 received
Sulconazole Miconazole sulconazole and 34 received miconazole; among fhe
14 with ecthyma, 8 received sulconazole and 6 re-
Impetigo Ecthyma Impetigo Ecthyma ceived miconazole. The demographic characteristics
Diagnosis 32 8 34 6
and bacterial culture results for the two treatment
Age (years)*
groups are summarized in Table 1. There were no
Mean 21 45 26 55 significant differences in demographic characteristics
Range 1-65 20-69 1-57 30-74 between the two treatment groups for patients with
Sex (%)t either initial disease. All patients completed the 2-
Men 56 38 50 67
33
week study.
Women 44 63 50
Microorganism Isolated
at admission (%): Bacterial Culture Results
Group A |8-hemolytic
streptococci 19 13 6 33 At the beginning of the study, bacterial cultures
S. aureus 53 38 71 33 from all of the patients contained Group A (8-hemo-
Both microorganisms 28 50 24 33
lyfic streptococci or coagulase-positive S. aureus or
* Impetigo: p = 0.1060, (-test; ecthyma: p = 0.3397, t-test. both. Among fhe 66 pafients who began the trial with
t Impetigo: p = 0.6111, chi-square test; ecthyma: p = 0.5921, Fisher's a primary diagnosis of impetigo, by treatment day 4,
exact test. bacterial cultures from 22 (69%) of the 32 treated with
sulconazole and 17 (50%) of the 34 treated with mi-
any crusts, ulcers, vesicles, pustules, bullae, erythema, and
exudates was assessed as absent, mild, moderate, severe, or conazole were negative. By treatment day 7, bacterial
very severe. cultures from all 32 (100%) of the sulconazole-treated
At each of the three follow-up visits, the clinical status of patients and from 32 (94.1%) of the 34 miconazole-
the lesions was compared with that at the start of the trial. treated patients were negative. On treatment day 14,
Overall clinical status was evaluated as worse, not im- the bacterial culture from one miconazole-treated pa-
proved, minimally improved, significantly improved, or
completely healed.
tient (3.3%) was still positive.
The investigator based his overall evaluation of the thera- Among the 14 patients with a primary diagnosis of
peutic response of each patient on the rate of reversal of ecthyma, by treatment day 4, cultures from 4 (50%) of
positive bacterial cultures and on the amelioration of the
the 8 treated with sulconazole and 2 (33%) of the 6
pyodermal signs. Therapeutic response was rated as excel-
lent; very good; good; fair; or poor, none, or worse. treated with miconazole were negative, and by treat-
ment day 7, bacterial cultures from 7 (88%) of the
Statistical Analyses sulconazole-treated patients and 5 (83%) of the mi-
Data from fhe impetigo patients and data from the ecthy-
conazole-treated patients were negative; all were neg-
ma patients were analyzed separately. All of the statistical ative by day 14.
tests used were two-tailed. The t-test was used to assess For each disease, sulconazole reversed the culture
initial age differences between the two treatment groups, results more rapidly than miconazole and, although
the chi-square test was used to assess initial differences in clinically significant, these differences were not statis-
fhe sex distribution of the impetigo patients in each treat-
ment group, and Fisher's exact test was used to assess initial
tically significant.
differences in the sex distribution of the ecthyma patients in
each treatment group. Fisher's exact test was used to deter- Clinical Results
mine significant differences between the two treatment
groups in the rate of reversal of positive bacterial cultures The data ort crusts, ulcers, and on the severity of
and in the percentages of patients exhibiting pyodermal other pyodermal signs (vesicles, pustules, bullae,
signs. The Wilcoxon signed rank test was used to assess ulcers, and exudafe) were analyzed separately for im-
changes from admission severity scores within each treat- petigo patients and for ecthyma patients, as appro-
ment group. The Wilcoxon rank sum test was used to deter-
priate.
mine differences between the groups in (1) the effect of
treatment on the severity of pyodermal signs, (2) clinical Impetigo. Sulconazole was clearly superior to mi-
improvement, and (3) fhe investigator's overall evaluations conazole in reducing the severity of the impetigo
of drug efficacy at the end of treatment. Differences were crusts (Fig. 1), but the differences between the two
considered statistically significant when p ^ 0.05. treatments did not reach statistical significance. After
admission, both trial medications produced statisti-
Results
cally significant improvement of the combined sever-
Patient Population ity scores of the vesicles, pustules, bullae, and exudate
Eighty patients were admitted to the study, with 40 by treatment day 4, and improvement continued to be
assigned to receive each trial medication. Among the statistically significant throughout the study. Only one
718 INTERNATIONAL JOURNAL OF DERMATOLOCY December 1988 Vol. 27

100 100

80 80

(I)
CO

I 60 I 60
o
I 40 40

20 20

0 - _L 0 -
J_
Admission 14 Admission 14
Day of Visit Day of Visit
Fic. 1. Percentage of impetigo patients with crusts during treat- FIG. 2. Percentage of ecthyma patients with ulcers during treat-
ment with sulconazole nitrate 1 % cream or miconazole nitrate 2% ment with sulconazole nitrate 1 % cream or miconazole nitrate 2%
cream twice daily for 14 days. cream twice daily for 14 days.

miconazole-treated patient showed no improvement On treatment day 4, three (38%) of the sulcona-
by treatment day 4. zole-treated ecthyma patients and none of the mi-
By treatment day 7, the lesions of 5 (16%) of the conazole-treated ecthyma patients showed significant
sulconazole-treated patients and 1 (3%) of the mi- overall improvement; on treatment day 7, six (75%) of
conazole-treated patients had healed completely. By the sulconazole-treated patients and four (67%) of the
treatment day 14, the lesions of 20 (63%) of the sul- miconazole-treated patients showed significant over-
conazole-treated patients were healed completely, all improvement. On treatment day 14, the overall
and the rest (37%) showed significant improvement. improvement evaluation for ecthyma patients signifi-
The lesions of 17 (50%) of the miconazole-treated cantly favored sulconazole, both clinically and statisti-
patients had healed completely, those of 15 (44%) cally (p = 0.024). Of the sulconazole-treated patients,
had improved significantly, and those of 2 (6%) had five (63%) were rated completely healed and three
improved minimally. (38%) were rated significantly improved. All of the
Ecthyma. For patients with ecthyma, the clinical miconazole-treated patients had improved signifi-
status of crusts and the combined severity scores of cantly, but none had healed completely.
the vesicles, pustules, bullae, and exudate had im-
proved significantly by treatment day 4 for three Overall Therapeutic Response
(38%) of the eight sulconazole-treated patients. This Table 2 shows the results of the evaluations of the
improvement continued to be statistically significant overall therapeutic response of all the patients in the
throughout the trial. For the six miconazole-treated
patients, the clinical status of the crusts, and the com- TABLE 2. Investigator's Fvaluation of Overall Therapeutic Response
bined severity scores for the vesicles, pustules, bullae,
Treatment
and exudate showed no statistically significant
changes by treatment day 4. By treatment day 7, the Sulconazole Miconazole
status of the crusts had improved significantly, and by
treatment day 14, the combined status of the vesicles, Evaluation No. % No. %
pustules, bullae, and exudate had improved signifi- Worse, none, or poor 0 0.0 0 0.0
cantly. Figure 2 shows that by treatment day 14, the Fair 1 2.5 2 5.0
percentage of sulconazole-treated patients with ulcers Cood 7 17.5 16 40.0
had decreased significantly (from eight to three), but Very good 11 27.5 14 35.0
the number of miconazole-treated patients with Excellent 21 52.5 8 20.0
ulcers remained the same (six). The difference be- Total 40 100 40 100
tween the two treatment groups was statistically sig- p value* 0.002
nificant (p = 0.03). " Wilcoxon rank sum test.
No. 10 SULCONAZOLE VS. MICONAZOLE IN IMPETIGO AND ECTHYMA Nolting and Strauss 719

trial. The results of this analysis favored sulconazole, Systemic toxicity is rare when neomycin, poly-
both clinically and statistically (p = 0.002). myxin, or bacitracin is used topically; however, con-
Adverse Experiences. No sulconazole-treated pa- tact allergy can occur after the prolonged application
tient exhibited or reported any adverse experiences. of topical neomycin, and the widespread use of topi-
One miconazole-treated patient reported mild burn- cal neomycin can lead to resistant strains. Neosporin
ing lasting for 1 day on treatment day 5. and Cortisporin ointments are effective in treating
nonbullous staphylococcal infections, but bacitracin
Discussion and Conclusions ointment is not always effective in treating bullous
impetigo. Most widely used are bacitracin and combi-
Pyodermas are superficial skin infections. Group A
nations containing bacitracin and neomycin; neomy-
/3-hemolytic S. pyogenes and S. aureus are the patho-
cin may enhance the efficacy of other topical agents
gens most commonly isolated from pyodermas. Im-
against staphylococci but is of questionable value
petigo occurs in two forms: a vesiculopustular form
against streptococci.
caused by group A streptococci with staphylococci as
secondary invaders, and a bullous form caused by
Drug Names
group II coagulase-positive staphylococci.^ The vesi-
culopustular form has heretofore responded promptly miconazole nitrate: Monistat, Micatin
to penicillin or erythromycin, but bullous impetigo is sulconazole nitrate: Sulcosyn
often resistant to penicillin.^" Thus, although strepto-
coccal infections respond to penicillin, staphylococci References
have grown increasingly penicillin-resistant.^ By 1971, 1. Schachner L, Taplin D, Scott GB, et al. A therapeutic update of
75% of the staphylococci isolated from bullous impe- superficial skin infections. Pediatr Clin North Am
1983;30(2):397-404.
tigo lesions or lesions providing mixed cultures were 2. Gip L, Eorsstrom S. A double-blind parallel study of sulconazole
resistant to penicillin, and by 1980, over 85% were so nitrate 1 % cream compared vi'ith miconazole nitrate 2%
resistant.^^ In 1983, one investigative team found over cream in dermatophytoses. Mykosen. 1983;26:231-241.
3. Lassus A, Forstrom S, Salo O. A double-blind comparison of
that over 98% of the organisms cultured from pyo- sulconazole nitrate 1 % cream vi'ith clotrimazole 1 % cream in
dermal lesions were penicillin-resistant and presented the treatment of dermatophytoses. Br J Dermatol.
evidence that their data were not unreasonably dif- 1983;108:195-198.
4. Qadripur SA. Double-blind parallel comparison of sulconazole
ferent from those of other teams. Because it is difficult nitrate, 1 % cream and powder, with econazole, 1 % cream
to distinguish clinically between streptococcal and and powder, in the treatment of cutaneous dermatophyto-
staphylococcal skin infections, and because labora- ses. Current Therapeutic Research. 1984,35:753-758.
5. Tanenbaum L, Anderson C, Rosenberg M, et al. A new treat-
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nitrate 1.0 percent cream: a comparison with miconazole in
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has been oral or intramuscular penicillin. Oral cloxa- 7. Tanenbaum L, Clewe TH, Anderson C. Monograph for clinical
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matol. 1983;8:177-181.
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