Journal of Dermatological Treatment.

2013; 24: 70–74

ORIGINAL ARTICLE

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

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

Abstract
Although erythrasma is a superficial skin infection, there is no consensus on the treatment model of erythrasma. Objective: To
compare the efficacy 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 fifty-one patients over 18 years of age were included in this study.
Patients were randomized and divided into five groups. They received clarithromycin, erythromycin, fusidic acid cream, placebo
cream or placebo tablets. Patients were evaluated by Wood’s light reflection 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 Wood’s light reflection scores, the efficacy of
fusidic acid cream therapy was significantly higher than other therapies. When the efficacy of clarithromycin and erythromycin
therapy was compared, clarithromycin therapy was significantly 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 ef ficiency and better
patient’s compliance.

Key words: clarithromycin, erythrasma, erythromycin, fusidic acid

Introduction Patients and methods

Erythrasma is a superficial 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 inter-gluteal
regions (1–4). It is characterized by erythem-atous,
brown, scaly patches and maceration, and exhibits coral-
red fluorescence under Wood’s light (5–8). There is no
standard method of treatment for erythrasma, and a
variety of oral, topical and adjunc-tive 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, random-ized, 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 pre-ceding 2 weeks.
Before the study, the approval of the relevant ethics
committees was obtained. In accor-dance with the
Helsinki Declaration of Ethical Prin-ciples, the patients
were informed in writing and verbally, and informed
consents were obtained. The study was designed as a
double-blind, placebo-controlled randomized study. The
randomization was carried out centrally and five separate
groups were formed. In the first group, a single dose of 1
g/day of 500 mg clarithromycin tablets was applied.

Correspondence: Ergun Kusku, MD, Department of Dermatology, Dokuz Eylül 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

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 fifth 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 Wood’s light reflec-
tion with a Wood’s lamp and reflection scores were
recorded before and 48 h, 7 days and 14 days after the
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treatment. The Wood’s light reflection scores in all cases
of erythrasma, which was localized to the toe webs,
axillary, genitocrural and inframammary regions were
considered as follows: prominent red fluorescence – 2;
slight red fluorescence – 1; no fluorescence – 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 reflection scores were taken into
consideration. Only the patients whose reflection score
was 2 and who had a significant reflection were included
in this study. Patients were advised not to use another
sys-temic or topical medication during the treatment
period. Because of the possibility of being found
together and creating exacerbation of clinical symp-
toms, and for diagnostic purposes, direct mycological
examinations and cultures from the same areas were
performed. During the follow-up, patients were ques-
tioned 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 dis-tribution 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 Mann–
Whitney U-test was used for the differences between
groups, and Pearson’s chi-square analysis and Fisher’s
exact test were used for the comparisons according to
the methods of treat-ment, and p-values lower than 0.005
(<0.05) were considered to be statistically significant.
A study on the treatment of erythrasma 71
Results
The mean age of 151 patients (107 males and
44 females, 18–78 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 hyperhi-drosis in 45 patients (29.8%).
Based on the average Wood’s light reflection scores,
when the groups were compared according to the
effectiveness of the treatment at the 48th hour, oral
clarithromycin and fusidic acid were significantly more
effective than the placebo cream and placebo tablets.
Although oral erythromycin was found to be
significantly more effective than the placebo tablets (the
Mann–Whitney 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 signifi-cant
difference between the oral erythromycin and placebo
cream (the Mann–Whitney 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 significantly
superior to systemic clarithromycin and erythromycin.
Oral clarithromycin was found to be significantly more
effective than oral erythromycin at the 48th hour (the
Mann–Whitney 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 super-ior to the placebo cream and
placebo tablets. Fusidic acid cream was significantly
superior to the oral clarithromycin and erythromycin
tablets. There was no significant difference between the
clarithromycin and erythromycin tablets (the Mann–
Whitney 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
significantly superior to the placebo cream and placebo
tablets. Fusidic acid cream was significantly more
effective than clarithromycin and erythromycin tablets.
There was no significant difference between the
clarithro-mycin and erythromycin tablets (the Mann–
Whitney 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 Wood’s light reflection scores at each visit for the Discussion five groups.

Although there is no full consensus in the treatment of

48th hour Day 7 Day 14
erythrasma, there is a variety of oral, topical and
Erythromycin 1.250 ± 0.114a 0.700 ± 0.141 0.633 ± 0.143
b,d
adjunctive treatment models. These include systemic
Clarithromycin 0.833 ± 0.108a 0.450 ± 0.110 0.333 ± 0.105b,c applications such as erythromycin, tetracycline, chlor-
Fusidic acid 0.419 ± 0.101 0.032 ± 0.032 0.016 ± 0.016c,d amphenicol, clarithromycin and topical applications
Placebo cream 1.416 ± 0117 1.266 ± 0.128 1.266 ± 0.128 including clindamycin solution, Whitfield oinment
Placebo tablets 1.850 ± 0054 1.683 ± 0.100 1.683 ± 0100 consisting of benzoic acid and salicylic acid, antibac-
terial soaps and fusidic acid (9–13).
a In a double-blind, placebo-controlled study in which
Statistically significant difference between the clarithromycin
group and the erythromycin group at the 48th hour (p < 0.05). oral erythromycin and topical 2% fusidic acid cream
b
Statistically significant difference between the clarithromycin were used in 86 cases of erythrasma, it was found that
group and the erythromycin group on the day 14 (p = 0.154).
the rate of complete response was 77% in the
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c
Statistically significant difference between the fusidic acid group
and the clarithromycin group on the day 14 (p < 0.05). erythromycin group, 87% in the fusidic acid 2% cream
d
Statistically significant difference between the fusidic acid group group and 42% in the placebo group, and no statistically
and the erythromycin group on the day 14 (p < 0.05).
significant difference was found between these treatment
modalities (14). In another study, a twice-daily 14-day
partial response 0.5–1 and no response 1.5–2. Accord- application of 2% fusidic acid had the success rate of up
ingly, in the rate of the response to treatment at the end to 89%, and no recurrence was seen in the 40th post-
of the 14th day in the erythromycin group, complete treatment week (15). The use of clarithromycin in the
response was determined in 16 patients (53.3%), par-tial treatment of erythrasma was first described in a clinical
response was determined in 7 patients (23.4%) and no trial including three cases of erythrasma with
response was observed in 7 patients (23.4%). In the genitocrural localization and a 1-g/day single dose of
clarithromycin group, responses were as follows: com- clarithromycin provided the regression of pruritus at the
plete in 20 patients (66.7%), partial in 8 patients (26.6%) 48th hour and a full recovery in all three of the patients
and no response in 2 patients (6.7%). In the fusidic acid within 2 weeks. In this study, no serious adverse effect
group, complete response was observed in 30 patients was observed. Mild abdominal cramps was the only
(96.8%) and partial response was observed in 1 patient adverse effect attributable to clarithromycin use. It was
(3.2%) (Table II). concluded
score

2
1.6
Averagewood’s light reflection

1.2

0.8
0.4

Pretreatment 48th hour Day 7 Day 14

Treatment duration

Fusicid acid Erythromycin Clarithromycin

Placebo cream Placebo tablets

Figure 1. The reduction in the scores within each group. Significant 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 significantly more effective than systemic
clarithromycin and erythromycin and no significant therapeutic efficacy was observed between clarithromycin and erythromycin.

Table II. Clinical efficacy at the third visit.
Erythromycin Clarithromycin
fi n % n %
Ef cacy assessment
Complete response 16 53.3 20 66.7
Partial response 7 23.4 8 26.6
No response 7 23.4 2 6.7
Total 30 100 30 100
that a single dose of clarithromycin could constitude a
cheap, effective and safe therapy with perfect patient’s
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compliance and tolerability (16).
In our study, the efficacy of fusidic acid cream was
determined to be significantly higher than all other
methods of treatment. The efficacy of clarithromycin
was determined to be significantly higher than that of
erythromycin in the first 48 h, although there was no
significant difference between their efficacies 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, clarithro-mycin and
fusidic acid. The higher rate of effective-ness 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 steady-state concentration and the lower MIC
value of clar-ithromycin compared with erythromycin.
The values of minimal inhibitory concentration for the
Coryne-bacterium species of clarithromycin are lower
than for the other types of macrolide group antibiotics
such as erythtomycin and azithromycin (17). Hence,
clari-thromycin seems to be much more effective
particu-larly on the Corynebacterium species when
compared with other macrolides. However, there is no
clinical trial investigating the efficacy 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 post-antibiotic effect.
The post-antibiotic effect is defined 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 significantly higher
efficacy of fusidic acid cream treatment com-pared with
the other systemic treatments might be due to the
removal of coproporphyrin III from stratum corneum
during topical applications. In this study,
A study on the treatment of erythrasma 73
Fusidic acid Placebo cream Placebo tablets
n % n % n %
30 96.8 4 13.3 1 3.3
1 3.2 11 36.7 6 20.0
0 0.0 15 50 23 76.6
31 100 30 100 30 100
interdigital erythrasma was detected in the majority of
the patients. It has been reported that systemic ther-apy
alone may be insufficient in patients with inter-digital
erythrasma, and it is necessary to use 2% clindamycin
solution, 2% fusidic acid cream and Whitfield 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 Wood’s light reflec-tion 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 Coryne-bacterium
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 erythromy-cin,
clarithromycin and placebo tablets and fusidic acid,
placebo cream preparations: Kocak Pharmaceu-tical
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 conflicts of
interest. The authors alone are responsible for the
content and writing of the paper.
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