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A comparison between the effectiveness of

erythromycin, single-dose clarithromycin and
topical fusidic acid in the treatment of
erythrasma
ARTICLE in JOURNAL OF DERMATOLOGICAL TREATMENT SEPTEMBER 2011
Impact Factor: 1.67 DOI: 10.3109/09546634.2011.594870 Source: PubMed

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ORIGINAL ARTICLE

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A comparison between the effectiveness of erythromycin,

single-dose clarithromycin and topical fusidic acid in the treatment
of erythrasma

OKTAY AVCI, TANER TANYILDIZI & ERGUN KUSKU

Department of Dermatology, Dokuz Eyll University Faculty of Medicine, Izmir, Turkey

Abstract
Although erythrasma is a supercial skin infection, there is no consensus on the treatment model of erythrasma. Objective: To
compare the efcacy of erythromycin, single-dose clarithromycin and topical fusidic acid in the treatment of erythrasma in a
double-blind, placebo-controlled, randomized trial. Methods: Hundred and fty-one patients over 18 years of age were
included in this study. Patients were randomized and divided into ve groups. They received clarithromycin, erythromycin,
fusidic acid cream, placebo cream or placebo tablets. Patients were evaluated by Woods light reection scores and the initial
score values and the values on the days of 2, 7 and 14 were compared statistically. Results: According to the mean of Woods
light reection scores, the efcacy of fusidic acid cream therapy was signicantly higher than other therapies. When the efcacy
of clarithromycin and erythromycin therapy was compared, clarithromycin therapy was signicantly more effective than
erythromycin therapy at 48 h. However, there was no statistical difference on the days of 7 and 14. Conclusion: Topical fusidic
acid proved to be the most effective treatment; however, clarithromycin therapy may be an alternative regimen in the treatment
of erythrasma because of its efciency and better patients compliance.

Key words: clarithromycin, erythrasma, erythromycin, fusidic acid

Introduction

Patients and methods

Erythrasma is a supercial skin infection caused by

Corynebacterium minutissimum and often occurs in
intertriginous areas of the skin such as toe webs
and the inguinal, axillary, inframammary and intergluteal regions (14). It is characterized by erythematous, brown, scaly patches and maceration, and
exhibits coral-red uorescence under Woods light
(58). There is no standard method of treatment for
erythrasma, and a variety of oral, topical and adjunctive therapy models are used (9). In this study, our
aim was to compare the effectiveness of the treatments
with erythromycin, single-dose clarithromycin and
topical fusidic acid with the double-blind, randomized, placebo-controlled method in patients with
erythrasma.

A total of 151 adult patients over 18 years of age with

the diagnosis of erythrasma were involved in this
study. Exclusion criteria comprised pregnancy and
breast-feeding, allergy to macrolides or fusidic acid,
antibiotic and antifungal treatments within the preceding 2 weeks. Before the study, the approval of the
relevant ethics committees was obtained. In accordance with the Helsinki Declaration of Ethical Principles, the patients were informed in writing and
verbally, and informed consents were obtained. The
study was designed as a double-blind, placebocontrolled randomized study. The randomization
was carried out centrally and ve separate groups
were formed. In the rst group, a single dose of
1 g/day of 500 mg clarithromycin tablets was applied.

Correspondence: Ergun Kusku, MD, Department of Dermatology, Dokuz Eyll University, Balcova, 35340 Izmir, Turkey. Tel: 90 232 4123852.
Fax: 90 232 4646309. E-mail: ergun.kusku@deu.edu.tr

(Received 3 March 2011; accepted 4 May 2011)

ISSN 0954-6634 print/ISSN 1471-1753 online
2013 Informa Healthcare USA on behalf of Informa UK Ltd.
DOI: 10.3109/09546634.2011.594870

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A study on the treatment of erythrasma

In the second group, 1 g/day dose of erythromycin
tablets was applied for 14 days. In the third group,
placebo tablets were applied for 14 days. In the
fourth group, fusidic acid cream 2% was applied
twice a day for 14 days and, in the fth group, placebo
cream was applied twice a day for 14 days. The
patients were intructed not to wash the rash for a
24-h-period before their each visit in order not to
remove the coproporphyrin III produced by the
causitive bacteria.
The patients were evaluated for Woods light reection with a Woods lamp and reection scores were
recorded before and 48 h, 7 days and 14 days after the
treatment. The Woods light reection scores in all
cases of erythrasma, which was localized to the
toe webs, axillary, genitocrural and inframammary
regions were considered as follows: prominent red
uorescence 2; slight red uorescence 1; no
uorescence 0. The evaluation was made by two
independent physicians who did not know which
patient was randomized into which group, and then
the average values of the scores that were determined
by these two evaluators were calculated. In cases
of erythrasma with bilateral localization, right-side
reection scores were taken into consideration.
Only the patients whose reection score was 2 and
who had a signicant reection were included in this
study. Patients were advised not to use another systemic or topical medication during the treatment
period. Because of the possibility of being found
together and creating exacerbation of clinical symptoms, and for diagnostic purposes, direct mycological
examinations and cultures from the same areas were
performed. During the follow-up, patients were questioned about the side effects of the medicaments and,
if present, the adverse effects were recorded.
Statistical analysis
At the end of the study, the scores obtained from the
groups were determined. Statistical analyses were
performed using SPSS 11.5 for Windows (SPSS,
Chicago, IL, USA). Even though the number of
patients was more than 30 in all groups, nonparametric
tests were used as a method of statistical analysis
because the variables were not persistent and the distribution of data was not in accordance with the normal
distribution in the histogram. Results of descriptive
statistical analysis are presented as mean standard
deviation. A MannWhitney U-test was used for the
differences between groups, and Pearsons chisquare analysis and Fishers exact test were used for
the comparisons according to the methods of treatment, and p-values lower than 0.005 (<0.05) were
considered to be statistically signicant.

71

Results
The mean age of 151 patients (107 males and
44 females, 1878 years of age) was determined to
be 50.68 12.972. Erythrasma was the commonest in
the toe webs (64.9%), which was followed by the
inguinal region (17.9%), in the axillary region
(14.6%) and in the inframammary region (2.6%).
Accompanying symptoms were as follows: pruritus
in 81 patients (53.6%), erythema in 109 patients
(72.2%), scaling in 145 patients (96%) and hyperhidrosis in 45 patients (29.8%).
Based on the average Woods light reection scores,
when the groups were compared according to the
effectiveness of the treatment at the 48th hour, oral
clarithromycin and fusidic acid were signicantly
more effective than the placebo cream and placebo
tablets. Although oral erythromycin was found to be
signicantly more effective than the placebo tablets
(the MannWhitney U-test, p < 0.05, and the mean
values of the scores were 1.250 0.114 and 1.850
0054, respectively), there was no statistically signicant difference between the oral erythromycin and
placebo cream (the MannWhitney U-test, p = 0.276,
and the mean values of the scores were 1.250
0.114 and 1.416 0117, respectively). Fusidic acid
was signicantly superior to systemic clarithromycin
and erythromycin. Oral clarithromycin was found to
be signicantly more effective than oral erythromycin
at the 48th hour (the MannWhitney U-test, p < 0.05,
and the mean values of the score were 0.833
0.108 and 1.250 0.114, respectively). On the 7th
day, oral clarithromycin and fusidic acid were superior to the placebo cream and placebo tablets. Fusidic
acid cream was signicantly superior to the oral
clarithromycin and erythromycin tablets. There was
no signicant difference between the clarithromycin
and erythromycin tablets (the MannWhitney U-test,
p = 0.255, and the mean values of the scores were
0.450 0.110 and 0.700 0141, respectively). On
the 14th day, clarithromycin, erythromycin and
fusidic acid cream were found to be signicantly
superior to the placebo cream and placebo tablets.
Fusidic acid cream was signicantly more effective
than clarithromycin and erythromycin tablets. There
was no signicant difference between the clarithromycin and erythromycin tablets (the MannWhitney
U-test, p = 0.154, and the mean values of the scores
were 0.333 0.105 and 0.633 0143, respectively)
(Table I).
The reduction in scores within each group is shown
in Figure 1.
Based on the scores at the end of the 14th day,
according to the response to treatment, the score values
were considered as follows: complete response 0,

72

O. Avci et al.

Table I. Average Woods light reection scores at each visit for the
ve groups.
48th hour
Erythromycin

Day 7

Day 14

1.250 0.114a 0.700 0.141 0.633 0.143b,d

Clarithromycin 0.833 0.108a 0.450 0.110 0.333 0.105b,c

Fusidic acid

0.419 0.101

0.032 0.032 0.016 0.016c,d

Placebo cream 1.416 0117

1.266 0.128 1.266 0.128

Placebo tablets 1.850 0054

1.683 0.100 1.683 0100

Statistically signicant difference between the clarithromycin

group and the erythromycin group at the 48th hour (p < 0.05).
Statistically signicant difference between the clarithromycin
group and the erythromycin group on the day 14 (p = 0.154).
c
Statistically signicant difference between the fusidic acid group
and the clarithromycin group on the day 14 (p < 0.05).
d
Statistically signicant difference between the fusidic acid group
and the erythromycin group on the day 14 (p < 0.05).

partial response 0.51 and no response 1.52. Accordingly, in the rate of the response to treatment at the end
of the 14th day in the erythromycin group, complete
response was determined in 16 patients (53.3%), partial response was determined in 7 patients (23.4%) and
no response was observed in 7 patients (23.4%). In the
clarithromycin group, responses were as follows: complete in 20 patients (66.7%), partial in 8 patients
(26.6%) and no response in 2 patients (6.7%). In
the fusidic acid group, complete response was observed
in 30 patients (96.8%) and partial response was
observed in 1 patient (3.2%) (Table II).

Average woods light reflection score

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Discussion
Although there is no full consensus in the treatment of
erythrasma, there is a variety of oral, topical and
adjunctive treatment models. These include systemic
applications such as erythromycin, tetracycline, chloramphenicol, clarithromycin and topical applications
including clindamycin solution, Whiteld oinment
consisting of benzoic acid and salicylic acid, antibacterial soaps and fusidic acid (913).
In a double-blind, placebo-controlled study in
which oral erythromycin and topical 2% fusidic
acid cream were used in 86 cases of erythrasma, it
was found that the rate of complete response was 77%
in the erythromycin group, 87% in the fusidic acid 2%
cream group and 42% in the placebo group, and no
statistically signicant difference was found between
these treatment modalities (14). In another study, a
twice-daily 14-day application of 2% fusidic acid had
the success rate of up to 89%, and no recurrence was
seen in the 40th post-treatment week (15). The use of
clarithromycin in the treatment of erythrasma was rst
described in a clinical trial including three cases
of erythrasma with genitocrural localization and a
1-g/day single dose of clarithromycin provided the
regression of pruritus at the 48th hour and a full
recovery in all three of the patients within 2 weeks.
In this study, no serious adverse effect was observed.
Mild abdominal cramps was the only adverse effect
attributable to clarithromycin use. It was concluded

1.6

1.2

0.8

0.4

0
Pretreatment

Day 7

48th hour

Day 14

Treatment duration
Fusicid acid

Erythromycin

Placebo cream

Placebo tablets

Clarithromycin

Figure 1. The reduction in the scores within each group. Signicant superiority of oral clarithromycin and topical fusidic acid to oral
erythromycin, placebo cream and placebo tablets (p < 0.05) at the 48th hour. The difference between clarithromycin and erythromycin
disappeared on the 7th day while fusidic acid appeared to be the most effective treatment. On the day 14, fusidic acid was found to be
signicantly more effective than systemic clarithromycin and erythromycin and no signicant therapeutic efcacy was observed between
clarithromycin and erythromycin.

A study on the treatment of erythrasma

73

Table II. Clinical efcacy at the third visit.

Erythromycin

Fusidic acid

Placebo cream

Placebo tablets

Efcacy assessment

Complete response

16

53.3

20

66.7

30

96.8

13.3

3.3

Partial response

23.4

26.6

3.2

11

36.7

20.0

No response

23.4

6.7

0.0

15

50

23

76.6

30

100

30

Total

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Clarithromycin

30

100

30

100

that a single dose of clarithromycin could constitude a

cheap, effective and safe therapy with perfect patients
compliance and tolerability (16).
In our study, the efcacy of fusidic acid cream was
determined to be signicantly higher than all other
methods of treatment. The efcacy of clarithromycin
was determined to be signicantly higher than that of
erythromycin in the rst 48 h, although there was no
signicant difference between their efcacies on the
7th and 14th days. At the end of the 14th day, it was
determined that there was a full recovery in the
majority of patients receiving erythromycin, clarithromycin and fusidic acid. The higher rate of effectiveness of the clarithromycin when compared with
erythromycin at the 48th hour may be due to a
high dose intake all at once and better bioavailability,
longer half-life, shorter time to reach steadystate concentration and the lower MIC value of clarithromycin compared with erythromycin. The values
of minimal inhibitory concentration for the Corynebacterium species of clarithromycin are lower than for
the other types of macrolide group antibiotics such as
erythtomycin and azithromycin (17). Hence, clarithromycin seems to be much more effective particularly on the Corynebacterium species when compared
with other macrolides. However, there is no clinical
trial investigating the efcacy of clarithromycin in
the treatment of erythrasma except one report
including only three patients (16). The effectiveness
of 1 g/day single dose of clarithromycin in erythrasma
can be explained with its superior features such
as bioavailability, half-life and MIC value when
compared with erythromycin as well as its postantibiotic effect. The post-antibiotic effect is dened
as a persistent supression of bacterial developement
following short-term drug administration. However,
there are no previously conducted studies on the
duration of the post-antibiotic effect of clarithromycin
on corynebacteria.
The success rate of 96.8% and the signicantly
higher efcacy of fusidic acid cream treatment compared with the other systemic treatments might be due
to the removal of coproporphyrin III from stratum
corneum during topical applications. In this study,

31

100

100

interdigital erythrasma was detected in the majority of

the patients. It has been reported that systemic therapy alone may be insufcient in patients with interdigital erythrasma, and it is necessary to use 2%
clindamycin solution, 2% fusidic acid cream and
Whiteld oinment consisting of 12% benzoic acid
and 6% salicylic acid, and antibacterial soaps in
conjunction with oral erythromycin (9). The results
of our trial and previous studies give the impression
that topical treatments can affect Woods light reection scores. Therefore, in future placebo-controlled
trials, a regulation such as an active systemic agent
plus placebo cream or a topical cream containing
active ingredient plus placebo tablets may give
more accurate results and possibly makes the
potential effect of the topical application equal in
each group. Undoubtfuly, the cultivation of Corynebacterium minutissimum or high-performance liquid
chromatography (18) could provide a much more
objective assesment; our laboratory was unable to
make these investigations and a grading system was
used for the assessment as described before (8,14).
In this study, it was found that 8 of the 30 patients
(26.7%) had abdominal pain and 1 had dyspepsia
receiving erythromycin. Six of the 30 patients (20%)
had the complaint of a metallic taste in the mouth,
2 (6.7%) had abdominal pain and 1 had dyspepsia in
the clarithyromycin group. One of the 30 patients had
pruritus and 1 had dyspepsia in the placebo tablet
group. The results of this study have shown that a
single dose of 1 g/day clarithromycin regimen is
an effective and safe alternative in the treatment of
erythrasma.
Acknowledgements
The authors would like to thank to the following
companies for their support on providing erythromycin, clarithromycin and placebo tablets and fusidic
acid, placebo cream preparations: Kocak Pharmaceutical Company, Mustafa Nevzat Pharmaceutical
Company, Bilim Pharmaceutical Company, Abdi
Ibrahim Pharmaceutical Company and Schering
Pharmaceutical Company.

74

O. Avci et al.

Declaration of interest: The authors report no

conicts of interest. The authors alone are responsible
for the content and writing of the paper.

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